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22 pages, 7694 KiB

Open AccessArticle

Sustainable Electropolymerization of Zingerone and Its C2 Symmetric Dimer for Amperometric Biosensor Films

by Myriam Caval, Maria Antonietta Dettori, Paola Carta, Roberto Dallocchio, Alessandro Dessì, Salvatore Marceddu, Pier Andrea Serra, Davide Fabbri and Gaia Rocchitta

Molecules 2023, 28(16), 6017; https://doi.org/10.3390/molecules28166017 - 11 Aug 2023

Viewed by 1298

Abstract

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the [...] Read more.

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the creation of these films for microsensors and biosensors. The purpose of this paper is to evaluate the performances of electrosynthesized polymers, layered by means of constant potential amperometry (CPA), of naturally occurring compound zingerone (ZING) and its dimer dehydrozingerone (ZING DIM), which was obtained by straight oxidative coupling reaction. The polymers showed interesting shielding characteristics against the main interfering species, such as ascorbic acid (AA): actually, polyZING exhibited an AA shielding aptitude comprised between 77.6 and 99.6%, comparable to that obtained with PPD. Moreover, a marked capability of increased monitoring of hydrogen peroxide (HP), when data were compared with bare metal results, was observed. In particular, polyZING showed increases ranging between 55.6 and 85.6%. In the present work, the molecular structures of the obtained polymers have been theorized and docking analyses were performed to understand their peculiar characteristics better. The structures were docked using the Lamarckian genetic algorithm (LGA). Glutamate biosensors based on those polymers were built, and their performances were compared with biosensors based on PPD, which is the most widespread polymer for the construction of amperometric biosensors. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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13 pages, 834 KiB

Open AccessArticle

A New HPLC-UV Method Using Hydrolyzation with Sodium Hydroxide for Quantitation of Trans-p-Hydroxycinnamic Acid and Total Trans-p-Hydroxycinnamic Acid Esters in the Leaves of Ligustrum robustum

by Shi-Hui Lu, Xiao-Na Liang, Xiao-Jin Nong, Ran Chen and Xiu-Xia Li

Molecules 2023, 28(14), 5309; https://doi.org/10.3390/molecules28145309 - 10 Jul 2023

Cited by 1 | Viewed by 1316

Abstract

Trans-p-hydroxycinnamic acid and its esters in the leaves of Ligustrum robustum might be a new resource to prevent diabetes and its complications. In the present study, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans- [...] Read more.

Trans-p-hydroxycinnamic acid and its esters in the leaves of Ligustrum robustum might be a new resource to prevent diabetes and its complications. In the present study, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in the leaves of L. robustum was developed, since it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. The extract of L. robustum was hydrolyzed with sodium hydroxide at 80 °C for 2 h, and then, hydrochloride was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL·min⁻¹ and detecting at 310 nm. The linear range for trans-p-hydroxycinnamic acid was 11.0–352.0 μg·mL⁻¹ (r² = 1.000). The limit of detection and limit of quantification were 2.00 and 6.07 μg·mL⁻¹, respectively. The relative standard deviations of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 103.3% ± 1.1%. It is the first HPLC method using hydrolyzation for quantification of many carboxylic esters. Finally, the method was used successfully to determine trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in various extracts of the leaves of L. robustum. The 60–70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96–3.99 mg·g⁻¹), and the 50–80% ethanol extracts of L. robustum displayed the highest contents of total trans-p-hydroxycinnamic acid esters (202.6–210.6 mg·g⁻¹). The method can be applied also to the quality control of the products of L. robustum. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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24 pages, 22159 KiB

Open AccessArticle

The Metschnikowia pulcherrima Clade as a Model for Assessing Inhibition of Candida spp. and the Toxicity of Its Metabolite, Pulcherrimin

by Dorota Kregiel, Karolina H. Czarnecka-Chrebelska, Hana Schusterová, Renáta Vadkertiová and Adriana Nowak

Molecules 2023, 28(13), 5064; https://doi.org/10.3390/molecules28135064 - 28 Jun 2023

Cited by 6 | Viewed by 1939

Abstract

Candidiasis is one of the most frequent infections worldwide. In this study, the antimicrobial properties of six strains belonging to the Metschnikowia pulcherrima clade were evaluated against twenty Candida and Candida-related Filobasidiella neoformans var. bacillispora (syn. Cryptococcus neoformans) of different origins, [...] Read more.

Candidiasis is one of the most frequent infections worldwide. In this study, the antimicrobial properties of six strains belonging to the Metschnikowia pulcherrima clade were evaluated against twenty Candida and Candida-related Filobasidiella neoformans var. bacillispora (syn. Cryptococcus neoformans) of different origins, employing the agar cross method. The toxic effect of pulcherrimin, a red metabolite that is responsible for the antimicrobial activities of Metschnikowia spp., was evaluated in various experimental models. The results of agar tests showed that the selected M. pulcherrima strains inhibited the growth of the Candida and non-Candida strains. However, inhibition was dependent on the strain and the environment. The presence of peptone, sodium silicate, and a higher incubation temperature decreased the antifungal action of the M. pulcherrima strains. Pulcherrimin showed cytotoxic and antiproliferative activity, with oxidative stress in cells leading to apoptosis. More research is needed on the mechanism of action of pulcherrimin on somatic cells. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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19 pages, 1671 KiB

Open AccessArticle

Do Ganoderma Species Represent Novel Sources of Phenolic Based Antimicrobial Agents?

by Milena Rašeta, Jovana Mišković, Eleonora Čapelja, Ewa Zapora, Aleksandra Petrović Fabijan, Petar Knežević and Maja Karaman

Molecules 2023, 28(7), 3264; https://doi.org/10.3390/molecules28073264 - 6 Apr 2023

Cited by 7 | Viewed by 2395

Abstract

Ganoderma species have been recognized as potential antimicrobial (AM) agents and have been used in traditional Chinese medicine (TCM) for a long time. The aim of this study is to examine the AM potential of autochthonous Ganoderma species (G. applanatum, G. [...] Read more.

Ganoderma species have been recognized as potential antimicrobial (AM) agents and have been used in traditional Chinese medicine (TCM) for a long time. The aim of this study is to examine the AM potential of autochthonous Ganoderma species (G. applanatum, G. lucidum, G. pfeifferi and G. resinaceum) from Serbia. The extraction of fungal material was prepared in different solvents (ethanol—EtOH, water—H₂O, chloroform—CHCl₃). Antibacterial activity (ABA) was determined using disk-diffusion, agar-well diffusion, and micro-dilution method, while for antifungal properties disk-diffusion and pour plate method were applied. Antiviral activity was tested on model DNA virus LK3 and determined by plaque assay. Statistical PCA analysis was applied for detection of correlation effects of phenolics and AM activities, while LC-MS/MS was performed for phenolics quantification. G. resinaceum CHCl₃ extract expressed the most potent ABA against P. aeruginosa (MIC = 6.25 mg/mL), probably due to presence of flavonoids and 2,5-dihydroxybenzoic acid. Among H₂O extracts, the highest ABA was determined for G. pfeifferi against both E. coli and S. aureus (21 and 19 mm, respectively). EtOH extracts of G. pfeifferi and G. resinaceum were the most effective against A. niger (23.8 and 20.15 mm, respectively), with special impact of phenolic acids and flavonoid isorhamnetin, while C. albicans showed the lowest susceptibility. The most potent antiviral inhibitor was G. lucidum (70.73% growth inhibition) due to the high amount of phenolic acids. To the best of our knowledge, this is the first report of a methodical AM profile of G. pfeifferi and G. resinaceum from the Balkan region including PCA analysis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Antifungal activity of G. pfeifferi and G. resinaceum EtOH extracts using disk-diffusion method. Abbreviations: GP—G. pfeifferi; GR—G. resinaceum. Full article ">Figure 2
Antifungal activity of G. pfeifferi and G. resinaceum EtOH extracts using pour plate method. Abbreviations: GP—G. pfeifferi; GR—G. resinaceum. Full article ">Figure 3
PCA of quantified phenolic compounds and AB activity of CHCl3 and H2O extracts of G. applanatum and G. resinaceum. Abbreviations: GA—G. applanatum; GR—G. resinaceum: MBC—minimal bactericidal concentration (mg/mL); MIC—minimal inhibitory concentration (mg/mL); BC—B. cereus; EC—E. coli; KP—K. pneumoniae; PA—P. aeruginosa; SA—S. aureus. Full article ">Figure 4
PCA of quantified phenolic compounds and antifungal activity of EtOH extracts of G. pfeifferi and G. resinaceum. Abbreviations: DD—disk-diffusion method; PP—pour plate method. Full article ">Figure 5
PCA of quantified phenolic compounds and AV activity of both H2O and EtOH extracts and EtOH extract solution in 5% DMSO of G. applanatum, G. lucidum, G. pfeifferi and G. resinaceum. Abbreviations: GA—G. applanatum; GL—G. lucidum; GP—G. pfeifferi; GR—G. resinaceum. Full article ">

16 pages, 4071 KiB

Open AccessArticle

Soy Isoflavones Induce Cell Death by Copper-Mediated Mechanism: Understanding Its Anticancer Properties

by Mohd Farhan, Mohamed El Oirdi, Mohammad Aatif, Insha Nahvi, Ghazala Muteeb and Mir Waqas Alam

Molecules 2023, 28(7), 2925; https://doi.org/10.3390/molecules28072925 - 24 Mar 2023

Cited by 13 | Viewed by 2813

Abstract

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which [...] Read more.

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which are present in soybeans and are regarded as potent chemopreventive agents. According to epidemiological studies, those who eat soy have a lower risk of developing certain cancers. Several mechanisms for the anticancer effects of isoflavones have been proposed, but none are conclusive. We show that isoflavones suppress prostate cancer cell growth by mobilizing endogenous copper. The copper-specific chelator neocuproine decreases the apoptotic potential of isoflavones, whereas the iron and zinc chelators desferroxamine mesylate and histidine do not, confirming the role of copper. Reactive oxygen species (ROS) scavengers reduce isoflavone-induced apoptosis in these cells, implying that ROS are cell death effectors. Our research also clearly shows that isoflavones interfere with the expression of the two copper transporter genes, CTR1 and ATP7A, in cancerous cells. Copper levels are widely known to be significantly raised in all malignancies, and we confirm that isoflavones can target endogenous copper, causing prooxidant signaling and, eventually, cell death. These results highlight the importance of copper dynamics within cancer cells and provide new insight into the potential of isoflavones as cancer-fighting nutraceuticals. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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24 pages, 4732 KiB

Open AccessArticle

Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening

by Duaa Eliwa, Amal Kabbash, Mona El-Aasr, Haytham O. Tawfik, Gaber El-Saber Batiha, Mohamed H. Mahmoud, Michel De Waard, Wagdy M. Eldehna and Abdel-Rahim S. Ibrahim

Molecules 2023, 28(4), 1583; https://doi.org/10.3390/molecules28041583 - 7 Feb 2023

Cited by 1 | Viewed by 2250

Abstract

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine [...] Read more.

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico. The metabolites were isolated from biotransformation of papaverine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002 and Cunninghamella blackesleeana NRRL 1369 via reduction, demethylation, N-oxidation, oxidation and hydroxylation reactions. Seven metabolites were isolated: namely, 3,4-dihydropapaverine (metabolite 1), papaveroline (metabolite 2), 7-demethyl papaverine (metabolite 3), 6,4′-didemethyl papaverine (metabolite 4), papaverine-3-ol (metabolite 5), papaverinol (metabolite 6) and papaverinol N-oxide (metabolite 7). The structural elucidation of the metabolites was investigated with 1D and 2D NMR and mass spectroscopy (EI and ESI). The molecular docking studies showed that metabolite 7 exhibited better binding interactions with the target enzymes PTP1B, α-glucosidase and PL than did papaverine. Furthermore, papaverinol-N-oxide (7) also displayed inhibition of α-glucosidase and lipase enzymes comparable to that of their ligands (acarbose and orlistat, respectively), as unveiled with an in silico ADMET profile, molecular docking and molecular dynamics studies. In conclusion, this study provides evidence for enhanced inhibition of PTP1B, α-glucosidase and PL via some papaverine fungal transformation products and, therefore, potentially better antidiabetic and antiobesity effects than those of papaverine and other known therapeutic agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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19 pages, 1312 KiB

Open AccessArticle

Insect Antifeedant Benzofurans from Pericallis Species

by Carmen E. Díaz, Braulio M. Fraga, Adriana G. Portero, Iván Brito, Carmen López-Balboa, Liliana Ruiz-Vásquez and Azucena González-Coloma

Molecules 2023, 28(3), 975; https://doi.org/10.3390/molecules28030975 - 18 Jan 2023

Cited by 1 | Viewed by 2040

Abstract

In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans [...] Read more.

In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans 10-ethoxy-11-hydroxy-10,11-dihydroeuparin (10), (-)-eupachinin A ethyl ether (12), 11,15-didehydro-eupachinin A (13), 10,12-dihydroxy-11-angelyloxy-10,11-dihydroeuparin (14), 2,4-dihydroxy-5-formyl-acetophenone (15) isolated for the first time as a natural product, 11-angelyloxy-10,11-dihydroeuparin (16), and 12-angelyloxyeuparone (17), along with several known ones (1–9, 11). In addition, the incubation of the abundant component, 6-hydroxytremetone (1), with the fungus Mucor plumbeus has been studied. Benzofurans in the tremetone series (1, 1a, 2–5, 18, 18a), the euparin series (6, 7, 7a, 8–10, 14, 16), and the eupachinin-type (11, 12) were tested for antifeedant effects against the insect Spodoptera littoralis. The antifeedant compounds (1, 4, 6, 11, 12) were further tested for postingestive effects on S. littoralis larvae. The most antifeedant compounds were among the tremetone series, with 3-ethoxy-hydroxy-tremetone (4) being the strongest antifeedant. Glucosylation of 1 by its biotransformation with Mucor plumbeus gave inactive products. Among the euparin series, the dihydroxyangelate 14 was the most active, followed by euparin (6). The eupachinin-type compounds (11, 12) were both antifeedants. Compounds 4, 11, and 12 showed antifeedant effects without postingestive toxicity to orally dosed S. littoralis larvae. Euparin (6) had postingestive toxicity that was enhanced by the synergist piperonyl butoxide. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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23 pages, 5504 KiB

Open AccessArticle

Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiO₂ in Mice: Targeting Inflammation, Oxidative Stress, Cytokine Production, and Nociceptor Sensory Neuron Activation

by Nayara A. Artero, Marília F. Manchope, Thacyana T. Carvalho, Telma Saraiva-Santos, Mariana M. Bertozzi, Jessica A. Carneiro, Anelise Franciosi, Amanda M. Dionisio, Tiago H. Zaninelli, Victor Fattori, Camila R. Ferraz, Maiara Piva, Sandra S. Mizokami, Doumit Camilios-Neto, Rubia Casagrande and Waldiceu A. Verri

Molecules 2023, 28(2), 872; https://doi.org/10.3390/molecules28020872 - 15 Jan 2023

Cited by 3 | Viewed by 2692

Abstract

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO₂) that trigger an [...] Read more.

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO₂) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone’s (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO₂, has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO₂, which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91^phox, GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1⁺ and TRPA1⁺ neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO₂, a component released upon wearing of prosthesis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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13 pages, 3311 KiB

Open AccessArticle

Effects of Fermented Citrus Peel on Ameliorating Obesity in Rats Fed with High-Fat Diet

by Chung-Hsiung Huang, Shun-Yuan Hsiao, Yung-Hsiang Lin and Guo-Jane Tsai

Molecules 2022, 27(24), 8966; https://doi.org/10.3390/molecules27248966 - 16 Dec 2022

Cited by 16 | Viewed by 3082

Abstract

Although citrus peel is a waste material, it contains a variety of bioactive components. As our preliminary findings showed that citrus peels fermented with Saccharomyces cerevisiae T1 contained increased levels of anti-obesity flavonoids, the objective of this study was to prepare fermented citrus [...] Read more.

Although citrus peel is a waste material, it contains a variety of bioactive components. As our preliminary findings showed that citrus peels fermented with Saccharomyces cerevisiae T1 contained increased levels of anti-obesity flavonoids, the objective of this study was to prepare fermented citrus peel and to investigate its effect on ameliorating obesity in Sprague Dawley (SD) rats fed with a high-fat diet (HFD). After fermentation, the amounts of limonene, nobiletin and 3-methoxynobiletin in citrus peel were markedly increased. SD rats were fed with an HFD for 10 weeks, followed by fermented citrus peel-containing HFD (0.3% or 0.9% w/w) for 6 weeks. Compared with those fed with an HFD alone, lower levels of body weight, visceral fat, body fat percentage, blood triglyceride, total cholesterol, low-density lipoprotein, malondialdehyde and hepatic adipose accumulation were observed in rats fed with fermented citrus peel. In parallel, hepatic levels of acetyl-CoA carboxylase and fatty acid synthase were diminished, and the level of hormone sensitivity lipase in visceral fat was elevated. These results reveal fermented citrus peel is a promising natural product with beneficial effects of alleviating HFD-induced obesity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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12 pages, 10628 KiB

Open AccessArticle

A Green Blue LED-Driven Two-Liquid-Phase One-Pot Procedure for the Synthesis of Estrogen-Related Quinol Prodrugs

by Elisa De Marchi, Lorenzo Botta, Bruno Mattia Bizzarri and Raffaele Saladino

Molecules 2022, 27(24), 8961; https://doi.org/10.3390/molecules27248961 - 16 Dec 2022

Cited by 1 | Viewed by 1802

Abstract

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as [...] Read more.

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as the two-liquid-phase reaction solvent, and in the presence of meso-tetraphenyl porphyrin as the photosensitizer. Two steroidal prodrugs 10β, 17β-dihydroxyestra-1,4-dien-3-one (DHED) and 10β-Hydroxyestra-1,4-diene-3,17-dione (HEDD) were obtained with high yield and selectivity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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8 pages, 1287 KiB

Open AccessArticle

Medicinal Properties of Anchusa strigosa and Its Active Compounds

by Ludmila Yarmolinsky, Arie Budovsky, Boris Khalfin, Leonid Yarmolinsky and Shimon Ben-Shabat

Molecules 2022, 27(23), 8239; https://doi.org/10.3390/molecules27238239 - 25 Nov 2022

Cited by 4 | Viewed by 1755

Abstract

Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification [...] Read more.

Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification of volatile compounds was performed by GC/MS analysis; HPLC, LC-ESI-MS, and MALDI-TOF-MS were also applied. Our results demonstrate that two specific combinations of compounds from A. strigosa extract significantly enhanced WH (p < 0.001). Several flavonoids of the plant extract, including quercetin 3-O-rutinoside, kaempferol, kaempferol 3-O-β-rhamnopyranosyl(1→6)-β-glucopyranoside, and kaempferol 3-O-α-rhamnopyranosyl(1→6)-β-galactopyranoside, were effective against drug-resistant microorganisms. In addition, all the above-mentioned compounds had antibiofilm activity against Escherichia coli and Salmonella enteritidis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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The effect of A. strigosa extract and compounds on wound healing in vitro. The rate of gap closure in cultured human dermal fibroblasts (scratch assay: in vitro model of wound healing) at 0, 10, 20, 24, 34 h after wound generation. Control was untreated fibroblasts. Crude extract was added at a concentration of 50 µg/mL. The combination 1 of tested compounds included: quercetin 3-O-rutinoside at a concentration of 50 µg/mL, ellagic acid at a concentration of 10 µg/mL and kaempferol 3-O-β-rhamnopyranosyl(1→6)-β-glucopyranoside at a concentration of 10 µg/mL. Combination 2 of the tested compounds included: kaempferol at a concentration of 10 µg/mL and ellagic acid at a concentration of 1 µg/mL. Data from three independent experiments are shown (mean ± SD). Full article ">Figure 2
Effect of A. strigosa extract and its phytochemicals on eradication of drug-resistant microorganisms (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens and Salmonella enteritidis). The phytochemicals were applied at concentration of 2 µM. Data from three independent experiments are shown. Full article ">Figure 3
Effect of quercitin 3-O-rutinoside, kaempferol and kaempferol glycoside derivatives on biofilm formation. The results are presented as the mean ± SE of the absorbance at 590 nm. The identified compounds and streptomycin were used at a concentration of 2 µM. Data from three independent experiments are shown. Full article ">

24 pages, 5194 KiB

Open AccessArticle

Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis

by Gaia Rocchitta, Carla Rozzo, Marina Pisano, Davide Fabbri, Maria Antonietta Dettori, Paolo Ruzza, Claudia Honisch, Roberto Dallocchio, Alessandro Dessì, Rossana Migheli, PierAndrea Serra and Giovanna Delogu

Molecules 2022, 27(22), 7942; https://doi.org/10.3390/molecules27227942 - 16 Nov 2022

Cited by 6 | Viewed by 2593

Abstract

Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared [...] Read more.

Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 µM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 µM, and by amperometric assay with IC₅₀ for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 µM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H₂O₂ in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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17 pages, 3145 KiB

Open AccessArticle

Characterization of Polyhydroxybutyrate, PHB, Synthesized by Newly Isolated Haloarchaea Halolamina spp.

by Nashwa Hagagy, Amna A. Saddiq, Hend M. Tag, Samy Selim, Hamada AbdElgawad and Rosa María Martínez-Espinosa

Molecules 2022, 27(21), 7366; https://doi.org/10.3390/molecules27217366 - 29 Oct 2022

Cited by 11 | Viewed by 3305

Abstract

This work aims to characterize the haloarchaeal diversity of unexplored environmental salty samples from a hypersaline environment on the southern coast of Jeddah, Saudi Arabia, looking for new isolates able to produce polyhydroxyalkanoates (PHAs). Thus, the list of PHA producers has been extended [...] Read more.

This work aims to characterize the haloarchaeal diversity of unexplored environmental salty samples from a hypersaline environment on the southern coast of Jeddah, Saudi Arabia, looking for new isolates able to produce polyhydroxyalkanoates (PHAs). Thus, the list of PHA producers has been extended by describing two species of Halolamina; Halolamina sediminis sp. strain NRS_35 and unclassified Halolamina sp. strain NRS_38. The growth and PHA-production were investigated in the presence of different carbon sources, (glucose, sucrose, starch, carboxymethyl cellulose (CMC), and glycerol), pH values, (5–9), temperature ranges (4–65 °C), and NaCl concentrations (100–350 g L⁻¹). Fourier-transform infra-red analysis (FT-IR) and Liquid chromatography–mass spectrometry (LC-MS) were used for qualitative identification of the biopolymer. The highest yield of PHB was 33.4% and 27.29% by NRS_35 and NRS_38, respectively, using starch as a carbon source at 37 °C, pH 7, and 25% NaCl (w/v). The FT-IR pattern indicated sharp peaks formed around 1628.98 and 1629.28 cm⁻¹, which confirmed the presence of the carbonyl group (C=O) on amides and related to proteins, which is typical of PHB. LC-MS/MS analysis displayed peaks at retention times of 5.2, 7.3, and 8.1. This peak range indicates the occurrence of PHB and its synthetic products: Acetoacetyl-CoA and PHB synthase (PhaC). In summary, the two newly isolated Halolamina species showed a high capacity to produce PHB using different sources of carbon. Further research using other low-cost feedstocks is needed to improve both the quality and quantity of PHB production. With these results, the use of haloarchaea as cell factories to produce PHAs is reinforced, and light is shed on the global concern about replacing plastics with biodegradable polymers. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1
Maximum likelihood phylogenetic tree based on 16S rRNA gene sequences showing the relationship between the potential PHB-producers NRS_35 and NRS_38 and closely related species from the GenBank database. The scale bar indicates 0.02 substitutions per nucleotide position. Full article ">Figure 2
Effect of physical factors on the growth of PHA-producer Halolamina sediminis strain NRS_35. Cells were grown in a PHA-production medium supplemented with glycerol (10 g L−1) as a carbon source; (A) temperature, (B) NaCl concentrations, (C) pH. For each time, different superscript letters indicate significant differences at the p < 0.05 level (one-way ANOVA and Duncan post hoc test) comparing physical factors at different levels. Full article ">Figure 3
Effect of physical factors on the growth of PHA-producer unclassified Halolamina sp. strain NRS_38 grown. Cells were grown in a PHA-production medium supplemented with glycerol (10 g L−1) as a carbon source; (A) temperature, (B) NaCl concentrations, and (C) pH. For each time, different superscript letters indicate significant differences at the p < 0.05 level (one-way ANOVA and Duncan post hoc test) comparing physical factors at different levels. Full article ">Figure 4
Growth and PHB yield by two new isolates Halolamina (A) NRS_35 and (B) NRS_38 under similar conditions with different carbon sources. Full article ">Figure 5
Recorded FT-IR patterns for extracted PHB/PHA (A) unclassified Halolamina sp. strain NRS_35, (B) Halolamina sediminis sp. strain NRS_38, and (C) standard PHB. Full article ">Figure 6
LC-MS spectra of Polyhydroxybutyrate standard diluted in Chloroform. Retention times (in minutes): (A) acetyl-CoA [RT: 5.219], (B) PhaB [RT: 6.077], (C) PhaC [RT: 7.353], (D) PHB [RT: 8.008]. Full article ">Figure 7
Spectrum from LC-MS/MS analysis of extracted PHB granules from (a) NRS_35 and (b) NRS_38. Full article ">

20 pages, 6817 KiB

Open AccessArticle

Effects of Salicylic Acid Concentration and Post-Treatment Time on the Direct and Systemic Chemical Defense Responses in Maize (Zea mays L.) Following Exogenous Foliar Application

by Yuanjiao Feng, Xiaoyi Wang, Tiantian Du, Yinghua Shu, Fengxiao Tan and Jianwu Wang

Molecules 2022, 27(20), 6917; https://doi.org/10.3390/molecules27206917 - 15 Oct 2022

Cited by 8 | Viewed by 2321

Abstract

Salicylic acid (SA) plays a critical role in allergic reactions of plants to pathogens and acquired systemic resistance. Thus far, although some research has been conducted on the direct effects of different concentrations of SA on the chemical defense response of treated plant [...] Read more.

Salicylic acid (SA) plays a critical role in allergic reactions of plants to pathogens and acquired systemic resistance. Thus far, although some research has been conducted on the direct effects of different concentrations of SA on the chemical defense response of treated plant parts (leaves) after at multiple post-treatments times, few research has reported on the systematic effects of non-treated parts (roots). Therefore, we examined direct and systemic effects of SA concentration and time following foliar application on chemical defense responses in maize variety 5422 with two fully expanded leaves. In the experiments, maize leaves were treated with different SA concentrations of 0.1, 0.5, 1.0, 2.5, 5.0 mM, and then, the presence of defense chemicals and enzymes in treated leaves and non-treated roots was measured at different time points of 3, 12, 24, 48, 72 h following SA foliar application. The results showed that direct and systemic effects of SA treatment to the leaf on chemical defense responses were related to SA concentration and time of measurement after spraying SA. In treated leaves, total phenolics content increased directly by 28.65% at the time point of 12 h following foliar application of 0.5 mM SA. DIMBOA (2,4-dihydroxy-7-methoxy-2H, 1, 4-benzoxazin-3 (4H)-one) content was directly enhanced by 80.56~551.05% after 3~72 h following 0.5~5.0 mM SA treatments. Polyphenol oxidase and superoxide dismutase activities were directly enhanced after 12~72 h following 0.5~5.0 mM SA treatments, whereas peroxidase and catalase activities were increased after 3~24 h following application of 1.0~5.0 mM SA. In non-treated roots, DIMBOA content and polyphenol oxidase activity were enhanced systematically after 3~48 h following 1.0~5.0 mM SA foliar treatments. Superoxide dismutase activities were enhanced after 3~24 h following 0.5~2.5 mM SA applications, but total phenolics content, peroxidase and catalase activity decreased in some particular concentrations or at the different times of measurement in the SA treatment. It can be concluded that SA foliar application at 1.0 and 2.5 mM produces strong chemical defense responses in maize, with the optimal induction time being 24 h following the foliar application. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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22 pages, 2847 KiB

Open AccessArticle

Dihydroxyquingdainone Induces Apoptosis in Leukaemia and Lymphoma Cells via the Mitochondrial Pathway in a Bcl-2- and Caspase-3-Dependent Manner and Overcomes Resistance to Cytostatic Drugs In Vitro

by Jennifer Baas, Sebastian Bieringer, Corazon Frias, Jerico Frias, Carolina Soehnchen, Corinna Urmann, Steffi Ritter, Herbert Riepl and Aram Prokop

Molecules 2022, 27(15), 5038; https://doi.org/10.3390/molecules27155038 - 8 Aug 2022

Cited by 4 | Viewed by 2831

Abstract

Isatis tinctoria and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived [...] Read more.

Isatis tinctoria and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived from tryptanthrin. We present here a new synthesis of hitherto neglected substituted quingdainones, which is very necessary due to their poor solubility behaviour, and a structure-dependent anti-leukaemic activity study of a number of compounds. Substituted α-phenylaminoacrylic acid was synthesised by hydrogen sulfide extrusion from an analogue mercaptoacetic acid, available from the condensation of rhodanin and a substituted tryptanthrin. It is shown that just improving water solubility does not increase anti-leukaemic activity, since a quingdainone carboxylic acid is inactive compared to dihydroxyquingdainone. The most effective compound, dihydroxyquingdainone with an AC₅₀ of 7.5 µmole, is further characterised, revealing its ability to overcome multidrug resistance in leukaemia cells (Nalm-6/BeKa) with p-glycoprotein expression. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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15 pages, 9360 KiB

Open AccessArticle

Anti-Inflammatory Effects of Auranamide and Patriscabratine—Mechanisms and In Silico Studies

by Kit-Kay Mak, Shiming Zhang, Jun Sheng Low, Madhu Katyayani Balijepalli, Raghavendra Sakirolla, Albena T. Dinkova-Kostova, Ola Epemolu, Zulkefeli Mohd and Mallikarjuna Rao Pichika

Molecules 2022, 27(15), 4992; https://doi.org/10.3390/molecules27154992 - 5 Aug 2022

Cited by 3 | Viewed by 3078

Abstract

Auranamide and patriscabratine are amides from Melastoma malabathricum (L.) Smith. Their anti-inflammatory activity and nuclear factor erythroid 2-related factor 2 (NRF2) activation ability were evaluated using Escherichia coli lipopolysaccharide (LPSEc)-stimulated murine macrophages (RAW264.7) and murine hepatoma (Hepa-1c1c7) cells, respectively. The cytotoxicity [...] Read more.

Auranamide and patriscabratine are amides from Melastoma malabathricum (L.) Smith. Their anti-inflammatory activity and nuclear factor erythroid 2-related factor 2 (NRF2) activation ability were evaluated using Escherichia coli lipopolysaccharide (LPSEc)-stimulated murine macrophages (RAW264.7) and murine hepatoma (Hepa-1c1c7) cells, respectively. The cytotoxicity of the compounds was assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was determined by measuring the nitric oxide (NO) production and pro-inflammatory cytokines (Interleukin (IL)-1β, Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, and IL-6) and mediators (NF-κB and COX-2). NRF2 activation was determined by measuring the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) quinone oxidoreductase 1 (NQO1), nuclear NRF2 and hemeoxygenase (HO)-1. In vitro metabolic stability was assessed using the mouse, rat, and human liver microsomes. The compounds were non-toxic to the cells at 10 μM. Both compounds showed dose-dependent effects in downregulating NO production and pro-inflammatory cytokines and mediators. The compounds also showed upregulation of NQO1 activity and nuclear NRF2 and HO-1 levels. The compounds were metabolically stable in mouse, rat and human liver microsomes. The possible molecular targets of NRF2 activation by these two compounds were predicted using molecular docking studies and it was found that the compounds might inhibit the Kelch domain of KEAP1 and GSK-3β activity. The physicochemical and drug-like properties of the test compounds were predicted using Schrodinger small molecule drug discovery suite (v.2022-2). Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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The cytotoxicity of test compounds on (A) murine macrophages (RAW 264.7); (B) murine hepatoma (Hepa-1c1c7) cells; (C) the anti-inflammatory activity of test compounds in LPSEc challenged RAW 264.7 cells. The results are expressed as the mean ± SD (n = 3). ****, p ≤ 0.0001 compared to LPSEc treated cells. The bars without annotation indicate the values are not significant with reference to the negative control. Full article ">Figure 2
The effect of auranamide and patriscabratine on pro-inflammatory cytokines (A) IL-6, (B) IL-1β, (C) IFN-γ, and (D) TNF-α; and mediators (E) COX-2 and (F) NF-κB. The activity of the test compounds was expressed as fold change. The results are expressed as mean ± SD (n = 3). **, p ≤ 0.01; ****, p ≤ 0.0001 compared to LPSEc treated cells. The bars without annotation indicate the values are not significant with reference to the negative control. Full article ">Figure 3
The effect of auranamide and patriscabratine on (A) NRF2 protein expression; (B) HO-1 protein expression; (C) NQO1 activity in whole cell lysate of Hepa-1c1c7 cells. The results are expressed as mean ± SD (n = 3). **, p ≤ 0.01; ****, p ≤ 0.0001 compared to LPSEc + 0.1% DMSO treatment. Full article ">

14 pages, 3177 KiB

Open AccessArticle

Pro-Apoptotic and Pro-Autophagic Properties of Cardenolides from Aerial Parts of Pergularia tomentosa

by Stefania Martucciello, Gaetana Paolella, Antonio Massimiliano Romanelli, Silvia Sposito, Lucia Meola, Antonietta Cerulli, Milena Masullo, Sonia Piacente and Ivana Caputo

Molecules 2022, 27(15), 4874; https://doi.org/10.3390/molecules27154874 - 29 Jul 2022

Cited by 5 | Viewed by 1850

Abstract

Pergularia tomentosa L., a milkweed tropical plant belonging to the family Asclepiadaceae, is a rich source of unusual cardiac glycosides, characterised by transfused A/B rings and a sugar moiety linked by a double link, generating a dioxanoid structure. In the present report, five [...] Read more.

Pergularia tomentosa L., a milkweed tropical plant belonging to the family Asclepiadaceae, is a rich source of unusual cardiac glycosides, characterised by transfused A/B rings and a sugar moiety linked by a double link, generating a dioxanoid structure. In the present report, five cardenolides isolated from the aerial parts of the plant (calactin, calotropin, 12β-hydroxycalactin, 12β,6′-dihydroxycalotropin, and 16α-hydroxycalotropin) were investigated for their biological effects on a human hepatocarcinoma cell line. Cell viability was monitored by an MTT assay. The occurrence of apoptosis was evaluated by detecting caspase-3 activation and chromatin fragmentation. The ability of these compounds to induce autophagy was analysed by monitoring two markers of the autophagic process, LC3 and p62. Our results indicated that all cardenolides had cytotoxic effects, with IC₅₀ ranging from 0.127 to 6.285 μM. All compounds were able to induce apoptosis and autophagy, calactin being the most active one. Some of them also caused a reduction in cell migration and a partial block of the cell cycle into the S-phase. The present study suggests that selected cardenolides from aerial parts of P. tomentosa, particularly calactin, possess potentially desirable properties for further investigation as anticancer agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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11 pages, 2247 KiB

Open AccessArticle

Insecticidal Activity of Organic Extracts of Solidago graminifolia and Its Main Metabolites (Quercetin and Chlorogenic Acid) against Spodoptera frugiperda: An In Vitro and In Silico Approach

by Verónica Herrera-Mayorga, José Alfredo Guerrero-Sánchez, Domingo Méndez-Álvarez, Francisco A. Paredes-Sánchez, Luis Víctor Rodríguez-Duran, Nohemí Niño-García, Alma D. Paz-González and Gildardo Rivera

Molecules 2022, 27(10), 3325; https://doi.org/10.3390/molecules27103325 - 22 May 2022

Cited by 13 | Viewed by 3120

Abstract

Spodoptera frugiperda (S. frugiperda) remains a global primary pest of maize. Therefore, new options to combat this pest are necessary. In this study, the insecticidal activity of three crude foliar extracts (ethanol, dichloromethane, and hexane) and their main secondary metabolites (quercetin [...] Read more.

Spodoptera frugiperda (S. frugiperda) remains a global primary pest of maize. Therefore, new options to combat this pest are necessary. In this study, the insecticidal activity of three crude foliar extracts (ethanol, dichloromethane, and hexane) and their main secondary metabolites (quercetin and chlorogenic acid) of the species Solidago graminifolia (S. graminifolia) by ingestion bioassays against S. frugiperda larvae was analyzed. Additionally, the extracts were phytochemically elucidated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Finally, an in silico study of the potential interaction of quercetin on S. frugiperda acetylcholinesterase was performed. Organic extracts were obtained in the range from 5 to 33%. The ethanolic extract caused higher mortality (81%) with a half-maximal lethal concentration (LC₅₀) of 0.496 mg/mL. Flavonoid secondary metabolites such as hyperoside, quercetin, isoquercetin, kaempferol, and avicularin and some phenolic acids such as chlorogenic acid, solidagoic acid, gallic acid, hexoside, and rosmarinic acid were identified. In particular, quercetin had an LC₅₀ of 0.157 mg/mL, and chlorogenic acid did not have insecticidal activity but showed an antagonistic effect on quercetin. The molecular docking analysis of quercetin on the active site of S. frugiperda acetylcholinesterase showed a −5.4 kcal/mol binding energy value, lower than acetylcholine and chlorpyrifos (−4.45 and −4.46 kcal/mol, respectively). Additionally, the interactions profile showed that quercetin had π–π interactions with amino acids W198, Y235, and H553 on the active site. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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15 pages, 324 KiB

Open AccessArticle

Evaluation of Immunotropic Activity of Iridoid-Anthocyanin Extract of Honeysuckle Berries (Lonicera caerulea L.) in the Course of Experimental Trichinellosis in Mice

by Jolanta Piekarska, Marianna Szczypka, Michał Gorczykowski, Anna Sokół-Łętowska and Alicja Z. Kucharska

Molecules 2022, 27(6), 1949; https://doi.org/10.3390/molecules27061949 - 17 Mar 2022

Cited by 4 | Viewed by 2048

Abstract

Our experiment determined the immunotropic activity of a natural, iridoid-anthocyanin extract from honeysuckle berry (Lonicera caerulea L.) (LC). The extract was administered to mice infected with Trichinella spiralis, orally at a dose of 2 g/kg bw, six times at 24 h [...] Read more.

Our experiment determined the immunotropic activity of a natural, iridoid-anthocyanin extract from honeysuckle berry (Lonicera caerulea L.) (LC). The extract was administered to mice infected with Trichinella spiralis, orally at a dose of 2 g/kg bw, six times at 24 h intervals (from day 3 prior to the infection to day 3 post-infection (dpi) with T. spiralis. At 5, 7, 14, and 21 dpi, samples of blood, spleen, and mesenteric lymph nodes (MLN) were collected, and isolated lymphocytes were analyzed by flow cytometry. The splenocyte proliferation was estimated with MTT testing, and the intensity of intestinal and muscle infection was also studied. LC stimulated the local immune system by inducing lymphocyte proliferation in the spleen 7 dpi and altered the percentage and absolute count of B (CD19⁺) and T (CD3⁺, CD8⁺) cells 7, 14, and 21 dpi in the peripheral blood. LC extract affected the dynamics of expulsion of adult Trichinella from the intestines and prolonged the intestinal phase of the infection but did not change the number of larvae in the muscles. These results suggest that Lonicera caerulea L. fruit extract modulates murine cellular immune response during intestinal phase of T. spiralis infection but shows no antiparasitic activity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

13 pages, 12197 KiB

Open AccessArticle

Efficient Extraction of Total Polyphenols from Apple and Investigation of Its SPF Properties

by Ocsana Opriş, Ildiko Lung, Maria-Loredana Soran, Adina Stegarescu, Tatiana Cesco, Aliona Ghendov-Mosanu, Paula Podea and Rodica Sturza

Molecules 2022, 27(5), 1679; https://doi.org/10.3390/molecules27051679 - 3 Mar 2022

Cited by 8 | Viewed by 3045

Abstract

The purpose of this study was to evaluate the sun protection factor (SPF) of cosmetic emulsions with the addition of hydroalcoholic apple extract. First, the total polyphenolic content, the antioxidant activity and SPF properties of the extracts obtained by sonication and refluxing were [...] Read more.

The purpose of this study was to evaluate the sun protection factor (SPF) of cosmetic emulsions with the addition of hydroalcoholic apple extract. First, the total polyphenolic content, the antioxidant activity and SPF properties of the extracts obtained by sonication and refluxing were evaluated. The two extraction methods were improved using the central composite design. For cosmetic emulsion that contained a different concentration of apple extract (10–40%), a SPF value between 0.51 and 0.90 was obtained. The most efficient apple extract was obtained by reflux using 50% ethanol and a 60 min extraction time. The concentrated extract was incorporated in a cosmetic emulsion whose SPF maximum was 0.90. Accordingly, due to photoprotective properties, the apple extract can be a candidate for use in cosmetic formulations. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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17 pages, 3846 KiB

Open AccessArticle

Isolation, Structural Characterization and Macrophage Activation Activity of an Acidic Polysaccharide from Raspberry Pulp

by Yongjing Yang, Xingxing Yin, Dejun Zhang, Jie Lu and Xuehong Wang

Molecules 2022, 27(5), 1674; https://doi.org/10.3390/molecules27051674 - 3 Mar 2022

Cited by 17 | Viewed by 2700

Abstract

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular [...] Read more.

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular weight (Mw) of 55582 Da, was isolated from the pulp of raspberries through DEAE-Sepharose Fast Flow and Sephadex G-200 chromatography. RPP-2a consisted of rhamnose, arabinose, galactose, glucose, xylose, galacturonic acid and glucuronic acid, with a molar ratio of 15.4:9.6:7.6:3.2:9.1:54.3:0.8. The results of Fourier transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometer (GC-MS), 1D-, and 2D-nuclear magnetic resonance (NMR) analyses suggested that the backbone of RPP-2a was primarily composed of →2)-α-L-Rhap-(1→, →2,4)-α-L-Rhap-(1→, →4)-α-D-GalAp-(1→, and →3,4)-α-D-Glcp-(1→ sugar moieties, with side chains of α-L-Araf-(1→, α-L-Arap-(1→, and β-D-Galp-(1→3)-β-D-Galp-(1→ residues linked to the O-4 band of rhamnose and O-3 band of glucose residues. Furthermore, RPP-2a exhibited significant macrophage activation activity by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and the expression of inducible nitric oxide synthase (iNOS) and cytokines at the transcriptional level in RAW264.7 cells. Overall, the results indicate that RPP-2a can be utilized as a potential natural immune-enhancing agent. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 4708 KiB

Open AccessArticle

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

by Sheng-Chieh Wang, Meng-Yang Chang, Jun-Ping Shiau, Ammad Ahmad Farooqi, Yu-Hsiang Huang, Jen-Yang Tang and Hsueh-Wei Chang

Molecules 2022, 27(5), 1576; https://doi.org/10.3390/molecules27051576 - 27 Feb 2022

Cited by 5 | Viewed by 2151

Abstract

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine [...] Read more.

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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12 pages, 1805 KiB

Open AccessArticle

Fraxinol Stimulates Melanogenesis in B16F10 Mouse Melanoma Cells through CREB/MITF Signaling

by Sun Young Moon, Kazi-Marjahan Akter, Mi-Jeong Ahn, Kwang Dong Kim, Jiyun Yoo, Joon-Hee Lee, Jeong-Hyung Lee and Cheol Hwangbo

Molecules 2022, 27(5), 1549; https://doi.org/10.3390/molecules27051549 - 25 Feb 2022

Cited by 8 | Viewed by 3007

Abstract

Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, [...] Read more.

Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, effectively stimulated melanogenesis. Treatment of B16-F10 cells with fraxinol increased the melanin content and tyrosinase activity in a concentration-dependent manner without causing cytotoxicity. Additionally, fraxinol enhanced the mRNA expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Fraxinol also increased the expression of microphthalmia-associated transcription factor at both mRNA and protein levels. Fraxinol upregulated the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). Furthermore, H89, a cAMP–dependent protein kinase A inhibitor, decreased fraxinol-induced CREB phosphorylation and microphthalmia-associated transcription factor expression and significantly attenuated the fraxinol-induced melanin content and intracellular tyrosinase activity. These results suggest that fraxinol enhances melanogenesis via a protein kinase A-mediated mechanism, which may be useful for developing potent melanogenesis stimulators. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Effects of fraxinol on cell viability and melanin production in B16F10 cells. (A) Chemical structure of fraxinol. (B) Cytotoxicity of fraxinol in B16F10 cells. Cells were incubated with various concentration of fraxinol (0, 20, 40, 60, 80, or 100 μM) for 48 h. Cell viability was measured using the MTT assay. The data are shown as the means ± SD; n = 3. (C) Effect of fraxinol on melanin accumulation in B16-F10 cells. Cells were treated with fraxinol (0, 20, 40, 60, 80, or 100 μM) for 48 h. (D) Effect of fraxinol and α-MSH on melanin content in B16-F10 cells. Cells were treated with fraxinol (100 μM) or α-MSH (100 nM) for 48 h. Cellular melanin contents were measured as described in the Materials and Methods section and expressed as percentages compared to the respective value obtained for the control cells (non-treated cells). The data are presented as the means ± SD; n = 3. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to 0 μM (no treatment). Full article ">Figure 2
Effects of fraxinol on tyrosinase activity in B16F10 cells. (A) B16F10 cells were treated with fraxinol (0, 20, 40, 60, 80, or 100 μM) for 48 h. The tyrosinase activity is presented as percentages compared to the respective value obtained for the control cells (no treatment). (B) Effect of fraxinol on mushroom tyrosinase activity in a cell free system was determined as described in the Material and Methods section. (C) Intracellular tyrosinase activity was observed using a light microscope after DOPA staining (scale bar, 100 μm). The data are presented as the means ± SD; n = 3. ** p < 0.01, *** p < 0.001 compared to 0 μM (no treatment). Full article ">Figure 3
Effects of fraxinol on mRNA and protein expression of tyrosinase, TRP-1, and TRP-2. B16-F10 cells were treated with fraxinol (100 μM). (A) TYR, (B) TRP-1, and (C) TRP-2 mRNA levels were determined using qRT-PCR. (D) Tyrosinase, TRP-1, and TRP-2 protein levels were determined using western blotting. The data are presented as the means ± SD; n = 2. *** p < 0.001 compared to the control (no treatment). Full article ">Figure 4
Effects of fraxinol on mRNA and protein expression of MITF and phosphorylation of CREB. B16F10 cells were treated with fraxinol (100 μM). (A) MITF mRNA expression was detected using qRT-PCR at 12 h after fraxinol treatment. (B) MITF protein expression was detected using western blotting at 24 h after fraxinol treatment. (C) Expression level of phosphorylated CREB was examined using western blotting at 4 h after fraxinol treatment. The data are presented as the means ± SD; n = 2. ** p < 0.01 compared to control (no treatment). Full article ">Figure 5
Effects of PKA inhibition on fraxinol-induced phosphorylation of CREB and expression of MITF mRNA and proteins in B16F10 cells. B16-F10 cells pretreated with or without H89 (10 μM) for 1 h were stimulated with fraxinol (100 μM). (A) Phosphorylation of CREB was detected at 4 h after fraxinol treatment using western blotting. (B) MITF mRNA expression was detected at 12 h after fraxinol treatment using qRT-PCR. (C) MITF protein expression was detected at 24 h after fraxinol treatment using western blot analysis. (D) Tyrosinase, TRP-1, and TRP2 protein expression was detected at 48 h after fraxinol treatment using western blotting. The data are presented as the means ± SD; n = 2. ** p < 0.01 compared to the fraxinol-treated group. Full article ">Figure 6
Effects of a PKA inhibitor on fraxinol-induced tyrosinase activation and melanin contents in B16F10 cells. B16F10 cells pretreated with or without H89 (10 μM) for 1 h were stimulated with fraxinol (100 μM) for 48 h. (A) Melanin content is expressed as percentages compared to the respective value obtained for the control cells (non-treated cells). (B) Tyrosinase activity is presented as a percentage compared to the respective value obtained for the control cells (no treatment). (C) Intracellular tyrosinase activity was observed using a light microscope after DOPA staining (scale bar, 100 μm). The data are presented as the means ± SD; n = 3. * p < 0.01, ** p < 0.001 compared to the fraxinol-treated group. Full article ">

10 pages, 903 KiB

Open AccessArticle

A Simple LC-MS/MS Method for the Quantification of PDA-66 in Human Plasma

by Rico Schwarz, Elisabeth R. D. Seiler, Sina Sender, Anahit Pews-Davtyan, Hugo Murua Escobar, Dietmar Zechner, Matthias Beller, Christian Junghanß and Burkhard Hinz

Molecules 2022, 27(3), 974; https://doi.org/10.3390/molecules27030974 - 1 Feb 2022

Cited by 1 | Viewed by 2289

Abstract

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine–threonine kinase glycogen synthase kinase 3β SB216763, [...] Read more.

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine–threonine kinase glycogen synthase kinase 3β SB216763, has shown preclinical antitumour effects in various cell lines, with the key pathways of its anticancer activity being cell cycle modulation, DNA replication and p53 signalling. For the monitoring of anticancer drug treatment in the context of therapeutic drug monitoring, the determination of plasma concentrations is essential, for which an LC-MS/MS method is particularly suitable. In the present study, a sensitive LC-MS/MS method for the quantification of the potential anticancer drug PDA-66 in human plasma with a lower limit of quantification of 2.5 nM is presented. The method was successfully validated and tested for the determination of PDA-66 in mouse plasma and sera. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1
Chemical structures, molecular formulae and molecular weights of PDA-66, SB216763 and the internal standard acridine orange. In the case of PDA-66 and acridine orange, the precursor ions are also indicated. Full article ">Figure 2
Sample calibration function, in which the quotient of the area of the quantifiers m/z 317.1 (PDA-66) and m/z 250.1 (internal standard) was formed at the indicated concentrations. Full article ">Figure 3
Chromatograms from LC-MS/MS analysis of (A) a blank sample, (B) a sample containing 2.5 nM PDA-66 (LLOQ), (C) a 7.5 nM PDA-66 standard sample and (D) a 100 nM PDA-66 standard sample. Shown are exemplary chromatograms of the quantification ions for PDA-66 and acridine orange (internal standard). Not shown are the qualifier ions for PDA-66 (m/z 230.2) and the internal standard (m/z 234.1). Full article ">Figure 4
Stability of PDA-66 as a function of time and temperature of storage, relative to controls freshly extracted and co-determined on the day of measurement (set to 100%). The ratio of the m/z values of the quantifiers m/z 317.1 (PDA-66) and m/z 250.1 (internal standard) was determined. Shown are the mean values ± SD of n = 8 (90 days, −80 °C extracted and evaporated samples) and n = 4 (remaining analysed samples) independent LC-MS/MS runs. Full article ">

20 pages, 8829 KiB

Open AccessArticle

Phytochemical Characterization, Antioxidant Activity, and Cytotoxicity of Methanolic Leaf Extract of Chlorophytum Comosum (Green Type) (Thunb.) Jacq

by Igor V. Rzhepakovsky, David A. Areshidze, Svetlana S. Avanesyan, Wolf D. Grimm, Natalya V. Filatova, Aleksander V. Kalinin, Stanislav G. Kochergin, Maria A. Kozlova, Vladimir P. Kurchenko, Marina N. Sizonenko, Alexei A. Terentiev, Lyudmila D. Timchenko, Maria M. Trigub, Andrey A. Nagdalian and Sergei I. Piskov

Molecules 2022, 27(3), 762; https://doi.org/10.3390/molecules27030762 - 24 Jan 2022

Cited by 33 | Viewed by 5652

Abstract

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents [...] Read more.

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents of the methanolic extract of leaves of C. comosum and biological properties of its different fractions. Water fraction was analyzed with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nineteen compounds belonging to different chemical classes were identified in the methanolic extract of leaves of C. comosum (Green type) (Thunb.) Jacques. In addition to several fatty acids, isoprenoid and steroid compounds were found among the most abundant constituents. One of the identified compounds, 4′-methylphenyl-1C-sulfonyl-β-d-galactoside, was not detected earlier in Chlorophytum extracts. The water fraction was toxic to HeLa cells but not to Vero cells. Our data demonstrate that methanolic extract of leaves of C. comosum can be a valuable source of bioactive constituents. The water fraction of the extract exhibited promising antitumor potential based on a high ratio of HeLa vs. Vero cytotoxicity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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11 pages, 4113 KiB

Open AccessArticle

Preparation of Hop Estrogen-Active Material for Production of Food Supplements

by Marcel Karabín, Tereza Haimannová, Kristýna Fialová, Lukáš Jelínek and Pavel Dostálek

Molecules 2021, 26(19), 6065; https://doi.org/10.3390/molecules26196065 - 7 Oct 2021

Cited by 5 | Viewed by 2937

Abstract

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for [...] Read more.

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for the production of estrogenically active food supplements has proved to be problematic. The aim of this study was to optimize the conditions (e.g., temperature, the length of the process and the amount of the catalyst) to produce 8-prenylnaringenin-rich material by the magnesium oxide-catalyzed thermal isomerization of desmethylxanthohumol. Under these optimized conditions, the yield of 8-prenylnaringenin was 29 mg per 100 gDW of product, corresponding to a >70% increase in its content relative to the starting material. This process may be applied in the production of functional foods or food supplements rich in 8-prenylnaringenin, which may then be utilized in therapeutic agents to help alleviate the symptoms of menopausal disorders. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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12 pages, 1508 KiB

Open AccessArticle

Isolation, Characterization, Complete Structural Assignment, and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

by Hamdoon A. Mohammed, Mohammed F. Abd El-Wahab, Usama Shaheen, Abd El-Salam I. Mohammed, Ashraf N. Abdalla and Ehab A. Ragab

Molecules 2021, 26(19), 5827; https://doi.org/10.3390/molecules26195827 - 26 Sep 2021

Cited by 11 | Viewed by 2747

Abstract

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma [...] Read more.

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC₅₀ values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G₁ cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC₅₀ values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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11 pages, 1297 KiB

Open AccessArticle

(+)-Usnic Acid as a Promising Candidate for a Safe and Stable Topical Photoprotective Agent

by Agnieszka Galanty, Justyna Popiół, Magdalena Paczkowska-Walendowska, Elżbieta Studzińska-Sroka, Paweł Paśko, Judyta Cielecka-Piontek, Elżbieta Pękala and Irma Podolak

Molecules 2021, 26(17), 5224; https://doi.org/10.3390/molecules26175224 - 28 Aug 2021

Cited by 12 | Viewed by 3184

Abstract

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, [...] Read more.

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, an in vitro model was created, comprising the determination of skin-penetrating properties via skin-PAMPA assay, safety assessment to normal human skin cells (keratinocytes, melanocytes, fibroblasts), and examination of photostability and photoprotective properties. Both enantiomers revealed comparable good skin-penetrating properties. Left-handed usnic acid was slightly more toxic to keratinocytes (IC₅₀ 80.82 and 40.12 µg/mL, after 48 and 72 h, respectively) than its right-handed counterpart. The latter enantiomer, in a cosmetic formulation, was characterized by good photoprotective properties and photostability, comparable to the UV filter octocrylene. Perhaps most interestingly, (+)-usnic acid combined with octocrylene in one formulation revealed enhanced photoprotection and photostability. Thus, the strategy can be considered for the potential use of (+)-usnic acid as a UV filter in cosmetic products. Moreover, the proposed model may be useful for the evaluation of candidates for UV filters. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 2138 KiB

Open AccessArticle

Chemical Profile, Antioxidant Properties and Antimicrobial Activities of Malaysian Heterotrigona itama Bee Bread

by Joseph Bagi Suleiman, Mahaneem Mohamed, Ainul Bahiyah Abu Bakar, Victor Udo Nna, Zaida Zakaria, Zaidatul Akmal Othman and Abdulqudus Bola Aroyehun

Molecules 2021, 26(16), 4943; https://doi.org/10.3390/molecules26164943 - 15 Aug 2021

Cited by 15 | Viewed by 3727

Abstract

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial [...] Read more.

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC₅₀ 1.914 µg/mL), followed by E. coli (MIC₅₀ 1.923 µg/mL), Shigella (MIC₅₀ 1.813 µg/mL) and Salmonella typhi (MIC₅₀ 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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pH of bee bread. BBE: bee bread ethanol extract, BBW: bee bread water extract. BBH: bee bread hot water extract, a p < 0.05 versus BBE. Full article ">Figure 2
H2O2 scavenging activity (a) and normalized absorbance of H2O2 (b). H2O2: hydrogen peroxide, BBE: bee bread ethanol extract (IC50: 1.338 µg/mL), BBW: bee bread water extract (IC50: 1.855 µg/mL), BBH: bee bread hot water extract (IC50: 1.945 µg/mL), VITC: Vitamin C (IC50: 1.874 µg/mL), QC: quercetin (IC50: 1.429 µg/mL). Full article ">Figure 3
DPPH radical scavenging activity (a) and normalized absorbance of DPPH activity (b). DPPH: 1,1 diphenyl 2 picrylhydrazyl, BBE: bee bread ethanol extract (IC50: 2.139 µg/mL), BBW: bee bread water extract (IC50: 2.694 µg/mL), BBH: bee bread hot water extract (IC50: 1.745 µg/mL), VITC: Vitamin C (IC50: 0.2607 µg/mL), QC: quercetin (IC50: 0.7787 µg/mL). Full article ">Figure 4
High-performance liquid chromatography analysis of BBE at 340 nm. Peak 1: gallic acid, peak 2: caffeic acid, peak 3: mangiferin, peak 4: trans-ferulic acid, peak 5: trans 3-hydroxycinnam acid, peak 6: 2-hydroxycinnam acid, peak 7: quercetin, 8: kaempferol, peak 9: apigenin. Full article ">Figure 5
Absorbance of various concentrations of (a): E. coli, (b) S. typhi, (c): Shigella and (d) K. pneumonia. The absorbance was measured at 0 h and after 24 h of incubation. T: tetracycline, A: amoxycillin, and E: erythromycin were used as positive controls. Full article ">Figure 6
Antimicrobial activity of BBE in (a) E. coli, (b) Salmonella typhi, (c) Shigella, (d) K. pneumonia, (e) Erythromycin (control), (f) normalized absorbance of E. coli, Salmonella typhi, Shigella and K. pneumonia from which the MIC50 were calculated. Full article ">Figure 6 Cont.
Antimicrobial activity of BBE in (a) E. coli, (b) Salmonella typhi, (c) Shigella, (d) K. pneumonia, (e) Erythromycin (control), (f) normalized absorbance of E. coli, Salmonella typhi, Shigella and K. pneumonia from which the MIC50 were calculated. Full article ">

14 pages, 25132 KiB

Open AccessArticle

The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation

by Canxia He, Luigina P. Buongiorno, Wei Wang, Jonathan C. Y. Tang, Natalizia Miceli, Maria Fernanda Taviano, Yujuan Shan and Yongping Bao

Molecules 2021, 26(16), 4919; https://doi.org/10.3390/molecules26164919 - 13 Aug 2021

Cited by 11 | Viewed by 2788

Abstract

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. [...] Read more.

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Effects of SFN on cell viability and cell migration in T24 cells. (A) T24 cell viability was determined by MTT cell proliferation assay. T24 cells were treated with serial concentrations of SFN (2.5–160 µM) for 6, 24, and 48 h. Each data point represents the mean ± standard deviation (SD) of three experiments, and each treatment was performed in six replicates. (B) Scratch assay. A plastic tip was used to scratch a clean wide wound area. Cells were then incubated with SFN for 24 and 48 h. Migration areas were photographed (×100) and calculated with Image J software (C). (D) Effects of SFN on cell migration. After starvation overnight, T24 cells were treated with SFN (0–40 μM) for 24 h. Cell migration was measured by cell migration assay. Results were compared to control. All data represent the mean ± SD of three experiments, each treatment in six replicates. Statistical significance versus control: * p < 0.05, ** p < 0.01. Full article ">Figure 2
Effect of SFN on Nrf2 expression and cell viability. (A) Effect of SFN (10 µM) on Nrf2 nuclear and cytosolic expression after treatment from 0 to 24 h. SAM68 was used as loading control for the nuclear fraction, β-Actin was used as loading control for the cytosolic fraction. (B) Nrf2 nuclear expression after SFN 2.5 µM treatment from 0 to 24 h. SAM68 was used as a loading control for the nuclear fraction. (C) T24 cell viability was tested after treatment with 10 µM SFN from 0 to 24 h. All data represent the mean ± SD of three experiments in which each treatment was performed in six replicates. Statistical significance versus control: * p < 0.05, ** p < 0.01. Full article ">Figure 3
Effect of SFN on GSH synthesis by targeting Nrf2 and γ-GCS in T24 cells. (A) Cellular GSH concentrations in T24 cells exposed to SFN. Subconfluent T24 cells were treated with SFN 5–20 µM. At the indicated time (0–24 h), control cells and those treated with SFN 5–20 µM were derivatized and the samples analyzed by HPLC. The significant difference was reported * p < 0.05, ** p < 0.01. (B) Cellular GSH levels in T24 cells exposed to L-Buthionine-sulfoximine (BSO) and SFN. T24 cells were incubated with dimethylsulphoxide (DMSO, vehicle) as control, SFN 10 µM and BSO 200 µM in cotreatment and separately, for 24 h. GSH level was evaluated using HPLC method and has been expressed as nmol/mg of proteins. Significantly difference in GSH concentrations monitored in untreated cells (vehicle), ** p < 0.01; significantly difference in GSH concentrations monitored in SFN treated cells, ## p < 0.01. (C) Effect of SFN (10 µM) treatment on GSH level in Nrf2 and γ-Glutamylcysteine Synthetase (γ-GCS) suppressed T24 cells. T24 cells were treated with Nrf2 siRNA or γ-GCS siRNA, then treated with SFN (10 µM) for 3 h and 24 h. No transfected cells with DMSO (final concentration 0.1%) for 3 h and 24 h were used as a vehicle. Cells transfected with AllStar siRNA and then treated with SFN 10 µM for 3 h and 24 h were used as negative control. Results are mean ± SD of 3 samples. A significant change from basal level is indicated with ** p < 0.01, # p < 0.05 is significantly different in GSH level at 24 h for Nrf2 siRNA and γ-GCS siRNA treatment compared with the AllStar group. Full article ">Figure 4
Effect of SFN on UGT and COX-2 expression in T24 cells. (A,B) Effect of SFN on UGT protein expression after treatment for 6 and 24 h. T24 cells were treated with SFN (2.5, 5, 10 and 20 µM) for 6 and 24 h. (C,D) Effect of SFN on COX-2 protein expression after treatment for 6 and 24 h. T24 cells were treated with SFN (2.5, 5, 10 and 20 µM) for 6 and 24 h. Data were normalized for β-Actin, and reported as fold variation with respect to the Vehicle group. Statistical significance versus control: * p < 0.05, ** p < 0.01. Full article ">Figure 5
Effect of SFN on the expression of Nrf2 and UGT and cell viability by targeting γ-GCS. T24 cells were incubated with SFN 10 µM and BSO 200 µM in co-treatment and separately for 24 h. Cells were treated with 0.1% DMSO as control. (A) Nrf2 nuclear expression in T24 cells exposed to BSO and SFN. SAM68 was used as a loading control. (B) UGT and COX-2 expression in T24 cells exposed to BSO and SFN. β-actin was used as loading control. (C) After treatment with BSO or SFN, cells were photographed with a microscope (×100). (D) After treatment with BSO or SFN, T24 cell viability was determined by MTT cell proliferation assay. ** p < 0.01 is represented with a significant difference compared with untreated cells (the Vehicle group). Statistical significance versus SFN treatment: * p < 0.05, ## p < 0.01. Full article ">Figure 6
A proposed mechanism of the inhibitory effects of SFN on cell growth and migration. Full article ">

13 pages, 304 KiB

Open AccessArticle

Analysis of Antioxidant Capacity and Antimicrobial Properties of Selected Polish Grape Vinegars Obtained by Spontaneous Fermentation

by Justyna Antoniewicz, Karolina Jakubczyk, Paweł Kwiatkowski, Dominika Maciejewska-Markiewicz, Joanna Kochman, Ewa Rębacz-Maron and Katarzyna Janda-Milczarek

Molecules 2021, 26(16), 4727; https://doi.org/10.3390/molecules26164727 - 4 Aug 2021

Cited by 11 | Viewed by 3276

Abstract

Nowadays, products of natural origin with health-promoting properties are increasingly more common. Research shows that fruit vinegars can be a source of compounds with antioxidant activity. Research on the total antioxidant capacity, total phenolic content, and antimicrobial properties against Staphylococcus aureus, Escherichia [...] Read more.

Nowadays, products of natural origin with health-promoting properties are increasingly more common. Research shows that fruit vinegars can be a source of compounds with antioxidant activity. Research on the total antioxidant capacity, total phenolic content, and antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans of grape vinegars were conducted. Moreover, gas chromatography was used to measure acetic acid content in the vinegars. The research material consisted of vinegars produced from five different grape varieties. For each variety, two variants were prepared: with and without the addition of sugar in the fermentation process. The highest antimicrobial activity against all micro-organisms was observed in vinegar produced from Solaris grapes with added sugar. The highest polyphenol content was observed in vinegar produced from the Prior grape variety with added sugar and the highest total antioxidant capacity is the Johanniter grape variety with added sugar. The vinegars examined in this study differed, depending on grape variety, in terms of antimicrobial properties, antioxidant capacity, total phenolic content, as well as acetic acid content. Sugar addition caused significant differences in the antioxidant capacity of vinegar samples. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

14 pages, 4522 KiB

Open AccessArticle

Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells

by Thao Quyen Cao, Nguyen Viet Phong, Jang Hoon Kim, Dan Gao, Hoang Le Tuan Anh, Viet-Duc Ngo, Le Ba Vinh, Young Sang Koh and Seo Young Yang

Molecules 2021, 26(15), 4444; https://doi.org/10.3390/molecules26154444 - 23 Jul 2021

Cited by 12 | Viewed by 2926

Abstract

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds [...] Read more.

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1−15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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The isolated compounds from M. charantia (1–15) and SB203580. Full article ">Figure 2
IL-6, IL-12 p40, and TNF-α proteins. (A) 2L3Y, (B) 1F42 and (C) 2AZ5. Full article ">Figure 3
Docking simulation of the interactions between compounds 3 (A), 4 (B), 6 (C), 11 (D), 12 (E), and SB203580 (F), respectively, and the 2L3Y protein of IL-6 expression. Full article ">Figure 3 Cont.
Docking simulation of the interactions between compounds 3 (A), 4 (B), 6 (C), 11 (D), 12 (E), and SB203580 (F), respectively, and the 2L3Y protein of IL-6 expression. Full article ">Figure 4
Docking simulation of the interactions between compounds 4–6 (A–C), 8 (D), 9 (E), 11 (F), 12 (G), and SB203580 (H), respectively, and the 1F42 protein of IL-12 p40 expression. Full article ">Figure 4 Cont.
Docking simulation of the interactions between compounds 4–6 (A–C), 8 (D), 9 (E), 11 (F), 12 (G), and SB203580 (H), respectively, and the 1F42 protein of IL-12 p40 expression. Full article ">Figure 5
Docking simulation of the interactions between compounds 4 (A), 6 (B), 9 (C), 11–14 (D–G), and SB203580 (H), respectively, and the 2AZ5 protein of TNF-α expression (A–H). Full article ">

12 pages, 2433 KiB

Open AccessArticle

IgE-Induced Mast Cell Activation Is Suppressed by Dihydromyricetin through the Inhibition of NF-κB Signaling Pathway

by Tsong-Min Chang, Tzu-Chih Hsiao, Ting-Ya Yang and Huey-Chun Huang

Molecules 2021, 26(13), 3877; https://doi.org/10.3390/molecules26133877 - 25 Jun 2021

Cited by 6 | Viewed by 3451

Abstract

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent [...] Read more.

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent or treat anaphylaxis. Dihydromyricetin (DHM) is a flavonoid compound with several pharmacological properties, including free radical scavenging, antithrombotic, anticancer, and anti-inflammatory activities. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of DHM in the DNP-IgE-sensitized human mast cell line, KU812. The cytokine levels and mast cell degranulation assays were determined by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of the DHM-mediated anti-allergic signaling pathway was analyzed by western blotting. It was found that treatment with DHM suppressed the levels of inflammatory cytokines TNF-α and IL-6 in DNP-IgE-sensitized KU812 cells. The anti-allergic inflammatory properties of DHM were mediated by inhibition of NF-κB activation. In addition, DHM suppressed the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mast cell-derived tryptase production. Our study shows that DHM could mitigate mast cell activation in allergic diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 814 KiB

Open AccessArticle

Conventional and Organic Honeys as a Source of Water- and Ethanol-Soluble Molecules with Nutritional and Antioxidant Characteristics

by Magdalena Polak-Śliwińska and Małgorzata Tańska

Molecules 2021, 26(12), 3746; https://doi.org/10.3390/molecules26123746 - 19 Jun 2021

Cited by 6 | Viewed by 3012

Abstract

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. [...] Read more.

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. The type of plants in the geographical area, climatic conditions and production method have a significantly influence on the nutritional quality of honey. However, this variability can influence consumer liking by the sensory attributes of the product. The aim of this work was to compare the most popular honeys from Poland in terms of nutritional value, organoleptic properties and antioxidant activity. In the study, five varieties of honey (honeydew, forest, buckwheat, linden and dandelion) from conventional and organic production methods were tested. The nutritional characteristics of honey samples included acidity, content of water, sugars, vitamin C, HMF and phenolics (total and flavonoids), while honey color, taste, aroma and consistency were investigated in the organoleptic characteristics. The antioxidant activity was determined in water- and ethanol-soluble honey extracts using DPPH and ORAC tests. The results showed that organoleptic and nutritional characteristics of popular Polish honeys differ significantly in relation to plant source and production method. The significant effect of honey variety on the content of HMF, saccharose and phenolics, as well as acidity and antioxidant capacity were noted. The impact of variety and variety × production method interaction was significant in the case of the content of vitamin C, glucose and fructose. A visible difference of buckwheat and forest honeys from other samples was observed. The highest content of total phenolics with antioxidant activity based on the SET mechanism was found in buckwheat honeys, while forest honeys were richer in flavonoids. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 999 KiB

Open AccessArticle

Impact of Harvest Conditions and Host Tree Species on Chemical Composition and Antioxidant Activity of Extracts from Viscum album L.

by Wioleta Pietrzak and Renata Nowak

Molecules 2021, 26(12), 3741; https://doi.org/10.3390/molecules26123741 - 19 Jun 2021

Cited by 37 | Viewed by 2895

Abstract

The content of plant secondary metabolites is not stable, and factors such as the region/location effect and seasonal variations have an impact on their chemical composition, especially in parasitic plants. Research in this area is an important step in the development of quality [...] Read more.

The content of plant secondary metabolites is not stable, and factors such as the region/location effect and seasonal variations have an impact on their chemical composition, especially in parasitic plants. Research in this area is an important step in the development of quality parameter standards of medicinal plants and their finished products. The effects of the time and place of harvest and the host tree species on the chemical composition and antioxidant activity of mistletoe extracts were investigated. Statistical tools were used to evaluate the results of the spectrophotometric and LC-ESI-MS/MS studies of the phenolic composition and antioxidant activity. The investigations indicate that the qualitative and quantitative composition, influencing the biological activity of mistletoe extracts, largely depends on the origin of the plant. The mistletoe extracts exhibited a rich phenol profile and high antioxidant activity. The chemometric analysis indicated that mistletoe collected from conifers (Viscum abietis and Viscum austriacum) had the most advantageous chemical composition and antioxidant activity. Moreover, the chemical profile and biological activity of the plant material were closely related to the climatic conditions and location of the harvested plant. Higher levels of phenolic compounds and high antioxidant activity were found in extracts obtained from plant material collected in cold weather with the presence of snow and less sunshine (autumn–winter period). Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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10 pages, 2384 KiB

Open AccessArticle

Interaction of Natural Compounds in Licorice and Turmeric with HIV-NCp7 Zinc Finger Domain: Potential Relevance to the Mechanism of Antiviral Activity

by Runjing Wang, Yinyu Wei, Meiqin Wang, Pan Yan, Hongliang Jiang and Zhifeng Du

Molecules 2021, 26(12), 3563; https://doi.org/10.3390/molecules26123563 - 10 Jun 2021

Cited by 4 | Viewed by 3170

Abstract

Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, [...] Read more.

Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, such as turmeric and licorice, which is widely used in traditional Chinese medicine. Liquiritin (LQ), isoliquiritin (ILQ), glycyrrhizic acid (GL), glycyrrhetinic acid (GA) and curcumin (CUR), which were the major active components, were herein chosen to study their interactions with HIV-NCp7 C-terminal zinc finger, aiming to find the potential active compounds and reveal the mechanism involved. The stacking interaction between NCp7 tryptophan and natural compounds was evaluated by fluorescence. To elucidate the binding mode, mass spectrometry was used to characterize the reaction mixture between zinc finger proteins and active compounds. Subsequently, circular dichroism (CD) spectroscopy and molecular docking were used to validate and reveal the binding mode from a structural perspective. The results showed that ILQ has the strongest binding ability among the tested compounds, followed by curcumin, and the interaction between ILQ and the NCp7 zinc finger peptide was mediated by a noncovalent interaction. This study provided a scientific basis for the antiviral activity of turmeric and licorice. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1
Sequence of the C-terminal zinc finger of HIV-NCp7 and the chemical structures of the compounds used in this study. Full article ">Figure 2
CD spectra of 100-μM ZF and 100-μM apopeptide. Full article ">Figure 3
(A) The fluorescence emission spectra of ZF upon incubation with different natural compounds. Spectra were recorded for 5-µM ZF after incubation with 30-µM complexes. (B) Fluorescence quenching ratio of ZF upon adding different ratios of natural compounds ((ZF)/(compounds)). Titration was performed with 5-µM ZF at RT. F represents the fluorescence intensity of ZF at 356 nm during titration, and F0 is the fluorescence intensity of ZF only at 356 nm. Full article ">Figure 4
ESI-MS spectra of the reaction mixture between ZF and ILQ. (A) 10 μM of zinc finger were incubated with 30-μM ILQ for 15 min. (B) 10 μM of zinc finger were incubated with 60-μM ILQ for 15 min. Full article ">Figure 5
Characterization of the ZF structure upon ILQ or CUR binding. (A) CD spectra of ZF at t = 2 h from the incubation with ILQ at 3:1 ([ILQ]/[ZF]) (B) CD spectra of ZF after the incubation with CUR for 2 h at 3:1 ([CUR]/[ZF]). Full article ">Figure 6
Molecular docking of HIV-NCp7 ZF with ILQ and CUR: (A,D) overview, (B,E) zoom in of the stacking region and (C,F) surface of the protein with ILQ and CUR, respectively. Full article ">

15 pages, 4940 KiB

Open AccessArticle

Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

by Victor Udo Nna, Ainul Bahiyah Abu Bakar, Zaida Zakaria, Zaidatul Akmal Othman, Nur Asyilla Che Jalil and Mahaneem Mohamed

Molecules 2021, 26(11), 3441; https://doi.org/10.3390/molecules26113441 - 5 Jun 2021

Cited by 12 | Viewed by 3951

Abstract

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic [...] Read more.

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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15 pages, 2349 KiB

Open AccessArticle

Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant

by Bruna Araujo Sousa, Osmar Nascimento Silva, William Farias Porto, Thales Lima Rocha, Luciano Paulino Silva, Ana Paula Ferreira Leal, Danieli Fernanda Buccini, James Oluwagbamigbe Fajemiroye, Ruy de Araujo Caldas, Octávio Luiz Franco, Maria Fátima Grossi-de-Sá, Cesar de la Fuente Nunez and Susana Elisa Moreno

Molecules 2021, 26(10), 3054; https://doi.org/10.3390/molecules26103054 - 20 May 2021

Viewed by 3712

Abstract

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for [...] Read more.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Full article ">Figure 1
Effects of AqGP in vitro against goat erythrocytes and murine cell line NIH/3T3. (A) The hemolytic activity of AqGP on goat erythrocytes was evaluated. (B) The effect of AqGP on cell viability of the cell line NIH/3T3 was evaluated by MTT assay. *** p < 0.05 difference as compared to the untreated group, which received only water (ANOVA followed by Bonferroni’s test); NS: not significant. Full article ">Figure 2
Effect of AqGP pre-treatment on hyperalgesia in mice. All animals were pre-treated with the AqGP extract at concentrations of 1, 5, or 10 mg/kg or acetylsalicylic acid (100 mg/kg) 15 min after the injection of nociceptive stimulant. (A) Hyperalgesia was induced by formalin (20 µL, 2.5%) in the sub-plantar region of the right paw. The number of licks was counted in two phases, phase 1 from 0 to 5 min, and phase 2 from 15 to 30 min. (B) Hyperalgesia induced by acetic acid (0.8%, 100 μL, i.p). The frequency of abdominal contortions was counted for 30 min. The results are expressed as the mean ± SEM of 5 animals. ** p < 0.05 when compared to the untreated control group (ANOVA followed by Bonferroni test). NS: not significant. Full article ">Figure 3
Anti-inflammatory bioassay-guided fractionation of AqGP. (A) Neutrophil migration to the peritoneal cavity in mice pre-treated with AqGP. (B) The migration of neutrophils to the peritoneal cavity was evaluated for mice pre-treated with fractions of AqGP collected from the ammonium sulfate precipitation process. (C) The migration of neutrophils to the peritoneal cavity in mice pre-treated with the peak three fraction (retention 29.9 min) obtained from fractionation by reverse phase chromatography of the 0–30% saturation fraction by ammonium sulfate of AqGP. (D) Anti-inflammatory activity after rechromatography in a hydrophobic affinity column of C4. Each experimental group had n = 5. Results are expressed as mean ± SEM of the number of neutrophils per mL. # p < 0.05 difference as compared to the untreated group injected with thioglycolate; * p < 0.05 difference as compared to the group treated with aqGP 1.0 mg/kg; ** p < 0.05 difference as compared to the group treated with aqGP fraction 0–30% (ANOVA followed by Bonferroni’s test); NS: not significant. Full article ">Figure 4
Steps for molecular identification of the bioactive compound isolated from AqGP, and classification as a thaumatin-like protein. Molecular mass profiles resulting from the first three fractionation steps. Where: M: molecular weight marker; 1: AqGP; 2: fraction 0–30%, precipitation with ammonium sulfate; 3: fraction 0–30%, precipitation with ammonium sulfate, dialyzed; 4: fraction with retention time of 29.9 min, obtained by HPLC C4 semipreparative column. The sequence alignment of the fragment retrieved from mass spectrometry with the PDB (Protein Data Bank) hits (the respective codes are between brackets) is: Zea mays [<a href="#B39-molecules-26-03054" class="html-bibr">39</a>], Solanum lycopersicum [<a href="#B40-molecules-26-03054" class="html-bibr">40</a>], Calotropis procera [<a href="#B41-molecules-26-03054" class="html-bibr">41</a>], Vitis vinífera [<a href="#B42-molecules-26-03054" class="html-bibr">42</a>], Musa acuminate [<a href="#B43-molecules-26-03054" class="html-bibr">43</a>], Nicotina tabacum [<a href="#B44-molecules-26-03054" class="html-bibr">44</a>], Actinidia deliciosa (Pavkov-Keller et al., unpublished), Thaumatococcus daniellii [<a href="#B45-molecules-26-03054" class="html-bibr">45</a>], and Triticum aestivum [<a href="#B46-molecules-26-03054" class="html-bibr">46</a>]. Positions with conserved residues (80%) are highlighted in green; positions with similar residues (80%) are highlighted in yellow. The predicted three-dimensional structure of the chimeric zeamatin harboring the fragment of AqGP. The fragment is highlighted in pink. The structure shows virtually no modification, compared to zeamatin (RMSD = 0.2 Å). The model shows a discrete optimized protein energy (DOPE) score of 0.3; in the Ramachandran plot, 87.4% and 12% of residues are in favored and allowed regions, respectively; with a Z-score on ProSA of −5.91. Full article ">

14 pages, 1426 KiB

Open AccessArticle

Occurrence and Determination of Carotenoids and Polyphenols in Different Paprika Powders from Organic and Conventional Production

by Alicja Ponder, Klaudia Kulik and Ewelina Hallmann

Molecules 2021, 26(10), 2980; https://doi.org/10.3390/molecules26102980 - 17 May 2021

Cited by 14 | Viewed by 3541

Abstract

Paprika powder is a good source of different carotenoids and polyphenols, which play a key role in preventing certain diseases (some kinds of cancer and cardiovascular diseases). They can also be used as natural food colorants. Organic production is characterized by strict rules, [...] Read more.

Paprika powder is a good source of different carotenoids and polyphenols, which play a key role in preventing certain diseases (some kinds of cancer and cardiovascular diseases). They can also be used as natural food colorants. Organic production is characterized by strict rules, but products obtained in this way contain more bioactive compounds, such as carotenoids and polyphenols. The aim of this study was to measure and identify carotenoids and polyphenols in different paprika samples (sweet, hot, smoked, and chili) obtained by organic and conventional production. Quantitative and qualitative carotenoid and polyphenols analysis showed that the experimental samples contained different concentrations of these compounds. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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22 pages, 2158 KiB

Open AccessArticle

Evaluation of Quality, Antioxidant Capacity, and Digestibility of Chickpea (Cicer arietinum L. cv Blanoro) Stored under N₂ and CO₂ Atmospheres

by Liliana Maribel Perez-Perez, José Ángel Huerta-Ocampo, Saúl Ruiz-Cruz, Francisco Javier Cinco-Moroyoqui, Francisco Javier Wong-Corral, Luisa Alondra Rascón-Valenzuela, Miguel Angel Robles-García, Ricardo Iván González-Vega, Ema Carina Rosas-Burgos, María Alba Guadalupe Corella-Madueño and Carmen Lizette Del-Toro-Sánchez

Molecules 2021, 26(9), 2773; https://doi.org/10.3390/molecules26092773 - 8 May 2021

Cited by 22 | Viewed by 3550

Abstract

The aim of this work was to monitor the quality, antioxidant capacity and digestibility of chickpea exposed to different modified atmospheres. Chickpea quality (proximal analysis, color, texture, and water absorption) and the antioxidant capacity of free, conjugated, and bound phenol fractions obtained from [...] Read more.

The aim of this work was to monitor the quality, antioxidant capacity and digestibility of chickpea exposed to different modified atmospheres. Chickpea quality (proximal analysis, color, texture, and water absorption) and the antioxidant capacity of free, conjugated, and bound phenol fractions obtained from raw and cooked chickpea, were determined. Cooked chickpea was exposed to N₂ and CO₂ atmospheres for 0, 25, and 50 days, and the antioxidant capacity was analyzed by DPPH (2,2′-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis-[3ethylbenzothiazoline-6-sulfonic acid]), and total phenols. After in vitro digestion, the antioxidant capacity was measured by DPPH, ABTS, FRAP (ferric reducing antioxidant power), and AAPH (2,2′-Azobis [2-methylpropionamidine]). Additionally, quantification of total phenols, and UPLC-MS profile were determined. The results indicated that this grain contain high quality and high protein (18.38%). Bound phenolic compounds showed the highest amount (105.6 mg GAE/100 g) and the highest antioxidant capacity in all techniques. Cooked chickpeas maintained their quality and antioxidant capacity during 50 days of storage at 4 and −20 °C under a nitrogen atmosphere. Free and conjugated phenolic compounds could be hydrolyzed by digestive enzymes, increasing their bioaccessibility and their antioxidant capacity during each step of digestion. The majority compound in all samples was enterodiol, prevailing the flavonoid type in the rest of the identified compounds. Chickpea contains biological interest compounds with antioxidant potential suggesting that this legume can be exploited for various technologies. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Water absorption and texture during the soaking time of raw chickpea. Full article ">Figure 2
Antioxidant capacity by radical DPPH of free, conjugated and bound phenols under different storage conditions. Control was air treatment. Full article ">Figure 3
Antioxidant capacity by radical ABTS of free, conjugated, and bound phenols under different storage conditions. Control was air treatment. Full article ">Figure 4
Quantification of total phenols of free, conjugated and bound phenols under different storage conditions. Control was air treatment. Full article ">Figure 5
Structures of phenolic compounds from chickpea identified by UPLC-MS. The images were taken from the database on polyphenol content in foods [<a href="#B53-molecules-26-02773" class="html-bibr">53</a>]. Full article ">Figure 6
Structures of phenolic compounds from chickpea identified by UPLC-MS in the in vitro gastrointestinal digestion. The images were taken from the database on polyphenol content in foods [<a href="#B53-molecules-26-02773" class="html-bibr">53</a>]. Full article ">

21 pages, 1217 KiB

Open AccessArticle

Comparison of the Effects of Conching Parameters on the Contents of Three Dominant Flavan3-ols, Rheological Properties and Sensory Quality in Chocolate Milk Mass Based on Liquor from Unroasted Cocoa Beans

by Bogumiła Urbańska, Hanna Kowalska, Karolina Szulc, Małgorzata Ziarno, Irina Pochitskaya and Jolanta Kowalska

Molecules 2021, 26(9), 2502; https://doi.org/10.3390/molecules26092502 - 25 Apr 2021

Cited by 12 | Viewed by 4715

Abstract

The content of polyphenols in chocolate depends on many factors related to the properties of raw material and manufacturing parameters. The trend toward developing chocolates made from unroasted cocoa beans encourages research in this area. In addition, modern customers attach great importance to [...] Read more.

The content of polyphenols in chocolate depends on many factors related to the properties of raw material and manufacturing parameters. The trend toward developing chocolates made from unroasted cocoa beans encourages research in this area. In addition, modern customers attach great importance to how the food they consume benefits their bodies. One such benefit that consumers value is the preservation of natural antioxidant compounds in food products (e.g., polyphenols). Therefore, in our study we attempted to determine the relationship between variable parameters at the conching stage (i.e., temperature and time of) and the content of dominant polyphenols (i.e.,catechins, epicatechins, and procyanidin B2) in chocolate milk mass (CMM) obtained from unroasted cocoa beans. Increasing the conching temperature from 50 to 60 °C decreased the content of three basic flavan-3-ols. The highest number of these compounds was determined when the process was carried out at 50 °C. However, the time that caused the least degradation of these compounds differed. For catechin, it was 2 h; for epicatechin it was 1 h; and for procyanidin it was 3 h. The influence of both the temperature and conching time on the rheological properties of chocolate milk mass was demonstrated. At 50 °C, the viscosity and the yield stress of the conched mass showed its highest value. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 2261 KiB

Open AccessArticle

Zinc Oxide Nanoparticles and Zinc Sulfate Impact Physiological Parameters and Boosts Lipid Peroxidation in Soil Grown Coriander Plants (Coriandrum sativum)

by Norma Ruiz-Torres, Antonio Flores-Naveda, Enrique Díaz Barriga-Castro, Neymar Camposeco-Montejo, Sonia Ramírez-Barrón, Fernando Borrego-Escalante, Guillermo Niño-Medina, Agustín Hernández-Juárez, Carlos Garza-Alonso, Pablo Rodríguez-Salinas and Josué I. García-López

Molecules 2021, 26(7), 1998; https://doi.org/10.3390/molecules26071998 - 1 Apr 2021

Cited by 24 | Viewed by 3756

Abstract

The objective of this study was to determine the oxidative stress and the physiological and antioxidant responses of coriander plants (Coriandrum sativum) grown for 58 days in soil with zinc oxide nanoparticles (ZnO NPs) and zinc sulfate (ZnSO₄) at [...] Read more.

The objective of this study was to determine the oxidative stress and the physiological and antioxidant responses of coriander plants (Coriandrum sativum) grown for 58 days in soil with zinc oxide nanoparticles (ZnO NPs) and zinc sulfate (ZnSO₄) at concentrations of 0, 100, 200, 300, and 400 mg of Zn/kg of soil. The results revealed that all Zn compounds increased the total chlorophyll content (CHLt) by at least 45%, compared to the control group; however, with 400 mg/kg of ZnSO₄, chlorophyll accumulation decreased by 34.6%. Zn determination by induction-plasma-coupled atomic emission spectrometry (ICP–AES) showed that Zn absorption in roots and shoots occurred in plants exposed to ZnSO₄ at all concentrations, which resulted in high levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA). Only at 400 mg/kg of ZnSO₄, a 78.6% decrease in the MDA levels was observed. According to the results, the ZnSO₄ treatments were more effective than the ZnO NPs to increase the antioxidant activity of catalase (CAT), ascorbate peroxidase (APX), and peroxidases (POD). The results corroborate that phytotoxicity was higher in plants subjected to ZnSO₄ compared to treatments with ZnO NPs, which suggests that the toxicity was due to Zn accumulation in the tissues by absorbing dissolved Zn⁺⁺ ions. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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(a) The TEM micrograph shows the morphology of the ZnO nanoparticles (NPs) in the sample, (b) histogram of the distribution of the NPs sizes, and (c) spectrogram of the chemical composition of the sample carried out through elemental analysis (EDS). Full article ">Figure 2
Zn absorption in root (A) and shoot (B) of coriander plants grown for 58 days in inert soil modified with zinc sulfate (ZnSO4) and zinc oxide nanoparticles (ZnO NPs) at concentrations of 0, 100, 200, 300, and 400 mg of Zn/kg of soil. Values are the average of five replications, means (n = 5). Bars represent the standard deviation of the mean. Different letters in each bar mean that the treatments were statistically different (Tukey, p ≤ 0.05). Full article ">Figure 3
(A) Chlorophyll-a (CHLa), (B) chlorophyll-b (CHLb), (C) total chlorophyll (CHLt), and carotenoids (D) of coriander plants grown for 58 days in inert soil modified with zinc sulfate (ZnSO4) and zinc oxide nanoparticles (ZnO NPs) at concentrations of 0, 100, 200, 300, and 400 mg of Zn/kg of soil. Values are the average of five replications, means (n = 5). Bars represent the standard deviation of the mean. Different letters in each bar mean that the treatments were statistically different (Tukey, p ≤ 0.05). Full article ">Figure 4
(A) Hydrogen peroxide (H2O2) and (B) malondialdehyde (MDA) content in shoots of coriander plants grown for 58 days in inert soil modified with zinc sulfate (ZnSO4) and zinc oxide nanoparticles (ZnO NPs) at 0, 100, 200, 300, and 400 mg of Zn/kg of soil. Values are the average of five replications, means (n = 5). Bars represent the standard deviation of the mean. Different letters in each bar mean that the treatments were statistically different (Tukey, p ≤ 0.05). Full article ">Figure 5
Activity of antioxidant enzymes in shoots of coriander plants grown for 58 days in inert soil modified with zinc sulfate (ZnSO4) and zinc oxide nanoparticles (ZnO NPs) at concentrations of 0, 100, 200, 300, and 400 mg of Zn/kg of soil. (A) Catalase activity (CAT), (B) Ascorbate peroxidase activity (APX), (C) Peroxidase activity (POD). Values are the average of five replications, means (n = 5). Bars represent the standard deviation of the mean. Different letters in each bar mean that the treatments were statistically different (Tukey, p ≤ 0.05). Full article ">

13 pages, 2123 KiB

Open AccessArticle

Insight into Gentisic Acid Antidiabetic Potential Using In Vitro and In Silico Approaches

by Hamza Mechchate, Imane Es-safi, Omkulthom Mohamed Al kamaly and Dalila Bousta

Molecules 2021, 26(7), 1932; https://doi.org/10.3390/molecules26071932 - 30 Mar 2021

Cited by 27 | Viewed by 4044

Abstract

Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the [...] Read more.

Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the antidiabetic potential of gentisic acid and highlight its mechanisms of action following in silico and in vitro approaches. The in silico study was intended to predict the interaction of GA with eight different receptors highly involved in the management and complications of diabetes (dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), α-amylase, peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase), while the in vitro study studied the potential inhibitory effect of GA against α-amylase and α-glucosidase. The results indicate that GA interacted moderately with most of the receptors and had a moderate inhibitory activity during the in vitro tests. The study therefore encourages further in vivo studies to confirm the given results. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Two-dimensional (2D) scheme of the gentisic acid (GA) interactions with protein tyrosine phosphatase 1B (PTP1B) receptor. Full article ">Figure 2
Two-dimensional scheme of the GA interactions with dipeptidyl-peptidase 4 (DPP4) receptor. Full article ">Figure 3
Two-dimensional scheme of the GA interactions with α-amylase receptor. Full article ">Figure 4
Two-dimensional scheme of the GA interactions with α-glucosidase receptor. Full article ">Figure 5
Two-dimensional scheme of the GA interactions with aldose reductase receptor. Full article ">Figure 6
Two-dimensional scheme of the GA interactions with glycogen phosphorylase receptor. Full article ">Figure 7
Results of α-amylase inhibitory activity. Values are expressed as mean ± standard deviation (SD, n = 3). Full article ">Figure 8
Results of α-glucosidase inhibitory activity. Values are expressed as mean ± SD (n = 3). Full article ">

17 pages, 342 KiB

Open AccessFeature PaperArticle

Antioxidant and Antibacterial Activity of Essential Oils and Hydroethanolic Extracts of Greek Oregano (O. vulgare L. subsp. hirtum (Link) Ietswaart) and Common Oregano (O. vulgare L. subsp. vulgare)

by Olga Kosakowska, Zenon Węglarz, Ewelina Pióro-Jabrucka, Jarosław L. Przybył, Karolina Kraśniewska, Małgorzata Gniewosz and Katarzyna Bączek

Molecules 2021, 26(4), 988; https://doi.org/10.3390/molecules26040988 - 13 Feb 2021

Cited by 49 | Viewed by 5306

Abstract

Greek oregano and common oregano were compared in respect of the antioxidant and antibacterial activity of the corresponding essential oils and hydroethanolic extracts in relation with their chemical profile. The chemical composition of essential oils was determined by GC-MS and GC-FID, while extracts [...] Read more.

Greek oregano and common oregano were compared in respect of the antioxidant and antibacterial activity of the corresponding essential oils and hydroethanolic extracts in relation with their chemical profile. The chemical composition of essential oils was determined by GC-MS and GC-FID, while extracts (phenolic acids and flavonoids fractions) were analyzed by HPLC-DAD. Based on given volatiles, the investigated subspecies represented two chemotypes: a carvacrol/γ-terpinene/p-cymene type in the case of Greek oregano and a sabinyl/cymyl type rich in terpinen-4-ol in common oregano. Within non-volatile phenolic compounds, rosmarinic acid appeared to dominate in both subspecies. Lithospermic acid B, chlorogenic acid and isovitexin were present only in Greek oregano extracts. However, the total content of flavonoids was higher in common oregano extracts. The essential oil and extract of Greek oregano revealed visibly stronger antibacterial activity (expressed as MIC and MBC) than common oregano, whereas the antioxidant potential (determined by DPPH, ABTS and FRAP) of these extracts was almost equal for both subspecies. In the case of Origanum plants, the potential application of essential oils and extracts as antiseptic and antioxidant agents in the food industry should be preceded by subspecies identification followed by recognition of their chemotype concerning both terpene and phenolics composition. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

14 pages, 3211 KiB

Open AccessArticle

Crataegus laevigata Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways

by Quynh T. N. Nguyen, Minzhe Fang, Mengyang Zhang, Nhung Quynh Do, Minseon Kim, Sheng Dao Zheng, Eunson Hwang and Tae Hoo Yi

Molecules 2021, 26(4), 869; https://doi.org/10.3390/molecules26040869 - 6 Feb 2021

Cited by 11 | Viewed by 3437

Abstract

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry [...] Read more.

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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The HPLC (high-performance liquid chromatography) result of chlorogenic acid (peak 1) and (−)-epicatechin standards (peak 2) (a) and the contents of chlorogenic acid and (−)-epicatechin in C. laevigata berry extract (CLE) (b). Full article ">Figure 2
DPPH radical (a) and ABTS•+ cation (b) scavenging activity of C. laevigata berry extract (CLE). The radical scavenging effect was presented as a percentage of that measured in the control group. Data are presented as the mean ± SD. ** and *** indicate the significant within-group differences (** p < 0.01 and *** p < 0.001, respectively). Full article ">Figure 3
Levels of reactive oxygen species (ROS) in human keratinocytes (HaCaTs) after 24 h of treatment were determined by flow cytometry with DCFH-DA dye. The number of cells is plotted versus the dichlorofluorescein fluorescence detected by the FL-2 channel (a). The relative ROS production of cells is presented as histograms (b). Values are shown as mean ± SD. # and * indicate significant differences from the non-LPS-treated control and LPS-induced control groups, respectively. # p < 0.05 vs. the non-treated group. *, **, and ***p < 0.05, 0.01, 0.001 vs. the LPS-treated control, respectively. Full article ">Figure 4
Effect of CLE on cell viability (a) and mRNA expression levels of IL-8 (b), RANTES (c), TARC (d), and MDC (e) under LPS stimulation. Values are shown as mean ± SD. # and * indicate significant differences from the non-LPS-treated control and LPS-induced control groups, respectively. # and ### p < 0.05 and 0.001 vs. the non-treated group, respectively. *, **, and *** p < 0.05, 0.01, and 0.001 vs. the LPS-treated control, respectively. Full article ">Figure 5
Effect of CLE on protein expression levels of phosphorylation of MAPKs (a) and AP-1 subunits c-Jun and c-Fos (b) under LPS stimulation. Values are shown as mean ± SD. # and * indicate significant differences from the non-LPS-treated control and LPS-induced control groups, respectively. #, ##, and ### p < 0.05, 0.01, and 0.001 vs. the non-treated group, respectively. *, **, and *** p < 0.05, 0.01, and 0.001 vs. the LPS-treated control, respectively. Full article ">Figure 6
Effect of CLE on protein expression levels of NFκB signaling pathway components under LPS stimulation. Values are shown as mean ± SD. # and * indicate significant differences from the non-LPS-treated control and LPS-induced control groups, respectively. ## and ### p < 0.01 and 0.001 vs. the non-treated group, respectively. *, **, and *** p < 0.05, 0.01, and 0.001 vs. the LPS-treated control, respectively. Full article ">Figure 7
Effect of CLE on protein expression levels of NFAT signaling (a) and COX-2 (b) under LPS stimulation. Values are shown as mean ± SD. # and * indicate significant differences from the non-LPS-treated control and LPS-induced control groups, respectively. #, ##, and ### p < 0.05, 001, and 0.001 vs. the non-treated group, respectively. *, **, and *** p < 0.05, 0.01, and 0.001 vs. the LPS-treated control, respectively. Full article ">

30 pages, 7987 KiB

Open AccessArticle

Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin

by Elwira Chrobak, Maria Jastrzębska, Ewa Bębenek, Monika Kadela-Tomanek, Krzysztof Marciniec, Małgorzata Latocha, Roman Wrzalik, Joachim Kusz and Stanisław Boryczka

Molecules 2021, 26(3), 737; https://doi.org/10.3390/molecules26030737 - 31 Jan 2021

Cited by 22 | Viewed by 3623

Abstract

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of [...] Read more.

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC₅₀ values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and K_DEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 2478 KiB

Open AccessArticle

Anticancer Potential of Sutherlandia frutescens and Xysmalobium undulatum in LS180 Colorectal Cancer Mini-Tumors

by Chrisna Gouws, Tanya Smit, Clarissa Willers, Hanna Svitina, Carlemi Calitz and Krzysztof Wrzesinski

Molecules 2021, 26(3), 605; https://doi.org/10.3390/molecules26030605 - 25 Jan 2021

Cited by 11 | Viewed by 4702

Abstract

Colorectal cancer remains to be one of the leading causes of death worldwide, with millions of patients diagnosed each year. Although chemotherapeutic drugs are routinely used to treat cancer, these treatments have severe side effects. As a result, the use of herbal medicines [...] Read more.

Colorectal cancer remains to be one of the leading causes of death worldwide, with millions of patients diagnosed each year. Although chemotherapeutic drugs are routinely used to treat cancer, these treatments have severe side effects. As a result, the use of herbal medicines has gained increasing popularity as a treatment for cancer. In this study, two South African medicinal plants widely used to treat various diseases, Sutherlandia frutescens and Xysmalobium undulatum, were evaluated for potential activity against colorectal cancer. This potential activity for the treatment of colorectal cancer was assessed relative to the known chemotherapeutic drug, paclitaxel. The cytotoxic activity was considered in an advanced three-dimensional (3D) sodium alginate encapsulated LS180 colorectal cancer functional spheroid model, cultured in clinostat-based rotating bioreactors. The LS180 cell mini-tumors were treated for 96 h with two concentrations of each of the crude aqueous extracts or paclitaxel. S. frutescens extract markedly decreased the soluble protein content, while decreasing ATP and AK per protein content to below detectable limits after only 24 h exposure. X. undulatum extract also decreased the soluble protein content, cell viability, and glucose consumption. The results suggested that the two phytomedicines have potential to become a source of new treatments against colorectal cancer. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 2686 KiB

Open AccessArticle

Caffeoylquinic Acid Derivatives of Purple Sweet Potato as Modulators of Mitochondrial Function in Mouse Primary Hepatocytes

by Andrea Torres, Lilia G. Noriega, Claudia Delgadillo-Puga, Armando R. Tovar and Arturo Navarro-Ocaña

Molecules 2021, 26(2), 319; https://doi.org/10.3390/molecules26020319 - 9 Jan 2021

Cited by 14 | Viewed by 3848

Abstract

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, [...] Read more.

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Total polyphenolic content (TPC), 5-CQA, 3,4-diCQA and 4,5-diCQA concentrations measured in 3 size of Mexican PSP: large (PSP-L), medium (PSP-M), and small (PSP-S). Each bar is the mean accompanied of the mean value ± SD of three independent experiments. Full article ">Figure 2
Chromatogram of CQA-derivatives from PSP and detected 320 nm. Full article ">Figure 3
Oxygen consumption rate (OCR) (A), mitochondrial function parameters (B), extracellular acidification rate (ECAR) (C), and glycolytic parameters (D) in mouse primary hepatocytes incubated for 18 h with different concentrations of 5-CQA. Each bar represents the mean ± SEM of three independent experiments and analyzed by one-way ANOVA followed by Tukey multiple comparison post hoc test. The differences were considered statistically significant at p < 0.05. Mean values with different lowercase letters show statistical differences between each other. Full article ">Figure 4
Oxygen consumption rate (OCR) (A), mitochondrial function parameters (B), extracellular acidification rate (ECAR) (C), and glycolytic parameters (D) in mouse primary hepatocytes incubated for 18 h with different concentrations of 3,4-diCQA. Each bar represents the mean ± SEM of three independent experiments and analyzed by one-way ANOVA followed by Tukey multiple comparison post hoc test. The differences were considered statistically significant at p < 0.05. Mean values with different lowercase letters show statistical differences between each other. Full article ">Figure 5
Oxygen consumption rate (OCR) (A), mitochondrial function parameters (B), extracellular acidification rate (ECAR) (C), and glycolytic parameters (D) in mouse primary hepatocytes incubated for 18 h with different concentrations of 4,5-diCQA. Each bar is the mean ± SEM of three independent experiments and analyzed by one-way ANOVA followed by Tukey multiple comparison post hoc test. The differences were considered statistically significant at p < 0.05. Mean values with different lowercase letters show statistical differences between each other. Full article ">Figure 6
Oxygen consumption rate (OCR) using BSA-conjugated palmitate as a main substrate for oxidation to estimate fatty acid oxidation in mouse primary hepatocytes incubated for 18 h with the indicated concentrations of 5-CQA (A), 3,4-diCQA (B), and 4,5-diCQA (C). Each bar is the mean ± SEM of three independent experiments and analyzed by one-way ANOVA followed by Tukey multiple comparison post hoc test. The differences were considered statistically significant at p < 0.05. Mean values with different lowercase letters show statistical differences between each other. Full article ">

12 pages, 3325 KiB

Open AccessArticle

Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells’ Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway

by Ko-Hsiu Lu, Heng-Hsiung Wu, Renn-Chia Lin, Ya-Chiu Lin, Peace Wun-Ang Lu, Shun-Fa Yang and Jia-Sin Yang

Molecules 2021, 26(1), 30; https://doi.org/10.3390/molecules26010030 - 23 Dec 2020

Cited by 28 | Viewed by 3378

Abstract

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, [...] Read more.

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, we investigated whether L48H37 represses human osteosarcoma cells’ biological behavior of migratory potential and invasive activities and attempted to delve into its underlying mechanisms. L48H37 up to 5 μM inhibited, without cytotoxicity, the motility, migration, and invasion of human osteosarcoma U2OS and MG-63 cells. In U2OS cells, the human protease array revealed an obvious decrease in urokinase plasminogen activator (uPA) expression after L48H37 treatment, and L48H37 actually reduced the level, protein and mRNA expression, and promoter activity of uPA dose-dependently. L48H37 decreased the phosphorylation of STAT3, JAK1, JAK2, and JAK3 in U2OS cells, but did not affect the phosphorylation of ERK, JNK, p38, and Akt. Using colivelin, an activator of STAT3, the L48H37-induced decrease in uPA and migratory potential could be countered as expected. Collectively, L48H37 represses the invasion and migration capabilities of U2OS and MG-63 cells by the suppression of uPA expression and the inhibition of JAK/STAT signaling. These results suggest that L48H37 may be a potential candidate for anti-metastatic treatment of human osteosarcoma. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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11 pages, 3604 KiB

Open AccessArticle

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma

by Cheng-Chen Huang, Po-Hui Wang, Yen-Ting Lu, Jia-Sin Yang, Shun-Fa Yang, Yu-Ting Ho, Chiao-Wen Lin and Chung-Han Hsin

Molecules 2020, 25(20), 4851; https://doi.org/10.3390/molecules25204851 - 21 Oct 2020

Cited by 11 | Viewed by 2448

Abstract

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of [...] Read more.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Effect of morusin on cell viability in human NPC cells. (A) The chemical structure of morusin. (B) HONE-1; (C) NPC-39; and (D) NPC-BM cells were treated with various concentrations (0–8 μM) of morusin for 24 h and then examined for cell viability. The data are presented as mean ± SD from at least triplicates independent experiments. Full article ">Figure 2
Effect of morusin on cell wound closure in human NPC cells. Wound healing assay evaluated the effect of morusin on cell motility of HONE-1 (A), NPC-39 (B) and NPC-BM (C) cells lines at various concentrations by microscope (at 100× magnification). The data are presented as mean ± SD from at least triplicates independent experiments. * p < 0.05 compared with untreated. Full article ">Figure 3
Morusin suppresses the cell migration and invasion of NPC cells. (A) HONE-1; (B) NPC-39; and (C) NPC-BM cells were pretreated with indicated concentrations of morusin. Cell migration and invasion were assayed at 24 h after seeding in a modified Boyden chamber with and without Matrigel coating, respectively. The number of cells was counted using a microscope at 100× magnification. Quantitative data are shown in the right panel. * p < 0.05 as compared with morusin-untreated controls. Full article ">Figure 4
Morusin inhibits the activity and expression of MMP-2 in NPC cells. HONE-1, NPC-39, and NPC-BM cells were treated with morusin (0–8 μM) for 24 h (A) Conditioned media were subjected to gelatin zymography for analyzing the activity of MMP-2. (B) Total cell lysates were prepared for determining the levels of MMP-2 protein. * p < 0.05, compared with the untreated control. Full article ">Figure 5
Effect of morusin on regulating the adhesion and MAPK signaling pathways. NPC-39 cells were treated with morusin (0–8 μM) for 24 h and cell lysates were subjected to Western blotting analysis to analyze the phosphorylation of: FAK, Src, and Akt for adhesion signaling (A); and ERK, JNK, and p38 for MAPK pathways (B). Densitometric analyses of kinase phosphorylation were conducted by ImageJ. * p < 0.05, compared with the vehicle group. Full article ">Figure 6
Inhibitory effect of ERK1/2 inhibitor (U0126) on MMP-2 activity and cell migration. (A) Human NPC-39 cell lines were pre-treated with U0126 (5 μM) for 1 h and then incubated in the presence or absence of morusin (4 μM) for 24 h, and the conditioned media were subjected to gelatin zymography for analyzing the activity of MMP-2. (B) The migration ability of cells was observed by Boyden chamber assay. * p < 0.05, compared with the vehicle group. # p < 0.05, compared with the U0126 treated group. Full article ">Figure A1
Screening of the inhibitory effects of morusin on multiple protease expressions in NPC-39 cells. Total cell lysates were prepared for determining the levels of MMP-9, E-cadherin, fibronectin, and vimentin protein. Full article ">

17 pages, 2458 KiB

Open AccessArticle

Pimpinella anisum Essential Oil Nanoemulsion Toxicity against Tribolium castaneum? Shedding Light on Its Interactions with Aspartate Aminotransferase and Alanine Aminotransferase by Molecular Docking

by Ahmed S. Hashem, Marwa M. Ramadan, Amira A. A. Abdel-Hady, Stefania Sut, Filippo Maggi and Stefano Dall’Acqua

Molecules 2020, 25(20), 4841; https://doi.org/10.3390/molecules25204841 - 20 Oct 2020

Cited by 17 | Viewed by 5335

Abstract

The insecticidal activity is the result of a series of complex interactions between toxic substances as ligands and insect’s enzymes as targets. Actually, synthetic insecticides used in pest control programs are harmful to the environment and may affect non-target organisms; thus, the use [...] Read more.

The insecticidal activity is the result of a series of complex interactions between toxic substances as ligands and insect’s enzymes as targets. Actually, synthetic insecticides used in pest control programs are harmful to the environment and may affect non-target organisms; thus, the use of natural products as pest control agents can be very attractive. In the present work, the toxic effect of aniseed (Pimpinella anisum L.) essential oil (EO) and its nanoemulsion (NE) against the red flour beetle Tribolium castaneum, has been evaluated. To assess the EO mode of action, the impact of sub-lethal concentrations of aniseed EO and NE was evaluated on enzymatic and macromolecular parameters of the beetles, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, total lipids and glucose. Finally, a molecular docking study was conducted to predict the mode of action of the major EO and NE components namely E-anethole, Limonene, alpha-himalachalene, trans-Verbenol and Linalool at binding site of the enzymes AST and ALT. Herein, the binding location of the main compounds in both proteins are discussed suggesting the possible interactions between the considered enzymes and ligands. The obtained results open new horizons to understand the evolution and response of insect-plant compounds interactions and their effect predicted at the molecular levels and side effects of both animal and human. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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21 pages, 5192 KiB

Open AccessArticle

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

by Recardia Schoeman, Natasha Beukes and Carminita Frost

Molecules 2020, 25(20), 4682; https://doi.org/10.3390/molecules25204682 - 14 Oct 2020

Cited by 33 | Viewed by 6199

Abstract

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol [...] Read more.

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G₂ phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 2773 KiB

Open AccessArticle

Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids

by Hsueh-Wei Tseng, Tobias Baumann, Huan Sun, Yane-Shih Wang, Zoya Ignatova and Nediljko Budisa

Molecules 2020, 25(19), 4418; https://doi.org/10.3390/molecules25194418 - 25 Sep 2020

Cited by 13 | Viewed by 5319

Abstract

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNA^Pyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants [...] Read more.

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNA^Pyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants have been developed during the last decade, enabling a substantial genetic code expansion, mainly with aliphatic pyrrolysine analogs. However, comparatively less progress has been made to expand the substrate range of MmPylRS towards aromatic amino acid residues. Therefore, we set to further expand the substrate scope of orthogonal translation by a semi-rational approach; redesigning the MmPylRS efficiency. Based on the randomization of residues from the binding pocket and tRNA binding domain, we identify three positions (V401, W417 and S193) crucial for ncAA specificity and enzyme activity. Their systematic mutagenesis enabled us to generate MmPylRS variants dedicated to tryptophan (such as β-(1-Azulenyl)-l-alanine or 1-methyl-l-tryptophan) and tyrosine (mainly halogenated) analogs. Moreover, our strategy also significantly improves the orthogonal translation efficiency with the previously activated analog 3-benzothienyl-l-alanine. Our study revealed the engineering of both first shell and distant residues to modify substrate specificity as an important strategy to further expand our ability to discover and recruit new ncAAs for orthogonal translation Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Chemical structure of Trp and Tyr analogs used in this study. 3-benzothienyl-l-alanine (Bta), 3-(1-naphthyl)-l-alanine (1-NaA), β-(1-azulenyl)-l-alanine (AzAla), 4-benzoyl-l-phenylalanine (Bpa), 1-methyl-l-tryptophan (1-MeW), 3-(2-naphthyl)-l-alanine (2-NaA), 3-chloro-l-tyrosine (3-ClY), 3-bromo-l-tyrosine (3-BrY), 3-iodo-l-tyrosine (3-IodY), and 3-methyl-l-tyrosine (3-MeY). Full article ">Figure 2
Key residues surrounding the active site pocket of MmPylRS for amino acid substrate recognition (PDB: 2Q7H [<a href="#B10-molecules-25-04418" class="html-bibr">10</a>]). The distance between N346 and the bound Pyl–AMP as indicated (red dashed line) is 2.7 Å. Full article ">Figure 3
In vivo amber suppression capacities and analytics of ncAA incorporation at amber sites with two different MmPylRS variants: (A) MmPylRS–SMG and (B) MmPylRS–GML. The library for ncAA incorporation was screened by monitoring sfGFP–R2TAG reporter fluorescence intensity. Details of the library screening with MmPylRS variants and ncAAs in 96-well plates are given in <a href="#app1-molecules-25-04418" class="html-app">Table S2</a> and S3. Each amino acid was supplied at a final concentration of 1 mM. (Control: no inducer and no ncAAs; no ncAAs: with inducer but without amino acids supplementation). Data in (B) is means ± SD (n = 3). Full article ">Figure 4
Deconvoluted ESI-MS profiles of the sfGFP–R2TAG reporter, revealing successful protein labelling with Trp and Tyr analogs. (A) Full-length sfGFP–R2_Bta and sfGFP–R2_1-NaA were produced by co-expression of MmPylRS–SMG. The calculated molecular mass of sfGFP–R2_Bta is 27,800.31 Da, whereas the observed mass is 27,801 Da. The calculated molecular mass of sfGFP–R2_1-NaA is 27,794.3 Da whereas the observed mass is 27,794 Da. (B) Full-length sfGFP–R2_3-ClY, sfGFP–R2_3-BrY, and sfGFP–R2_3-IodY were produced by co-expression of MmPylRS–GML. The calculated molecular mass of sfGFP–R2_3-ClY is 27,794.07 Da, whereas the observed mass is 27,795 Da. The calculated molecular mass of sfGFP–R2_3-BrY is 27,838.02 Da, whereas the observed mass is 27,839 Da. The calculated molecular mass of sfGFP–R2_3-IodY is 27,886 Da, whereas the observed mass is 27,886 Da. Full article ">Figure 5
Comparison of Bta incorporation efficiency. Fluorescence of the sfGFP–R2TAG reporter construct arises from amber suppression mediated by different MmPylRS–SMG variants. (A) MmPylRS–SMG variants combined with activity improving mutation sets introduced by site-directed mutagenesis. According to the observed total cell fluorescence, variant MmPylRS–KYR_SMG led to the production of more full-length sfGFP compared to other aaRS constructs. (B) MmPylRS–SMG variant performance when combined with different sets of efficiency-improving mutations. Ideally, aaRS construct expression should lead to a low background signal in the absence of ncAA supplementation (no ncAAs controls) and high efficiency Bta incorporation (observed by fluorescence intensity) when the ncAA is supplied. The control setup is without induction and ncAA supplementation; the no-ncAAs setup is with IPTG induction but without Trp or Bta supplementation, respectively. Data are means ± SD (n = 3). Full article ">Figure 6
Comparison of ncAA incorporation via different MmPylRS variants and impact of the activity-enhancing KYR mutation set (R61K, H63Y, and S193R). Fluorescence of the sfGFP–R2TAG reporter construct arises from amber suppression mediated by improved MmPylRS–SMG variants. (A) Trp analogs were incorporated into sfGFP by different MmPylRS variants (the last letter always indicating the substitution of aaRS position W417, mutation details in <a href="#app1-molecules-25-04418" class="html-app">Supplementary Table S1</a>; Control: without inducer and ncAAs). (B) Tyr analogs were incorporated into sfGFP by different MmPylRS variants (control: without inducer and ncAAs; the no-ncAAs setup is with IPTG induction but without Trp or Bta supplementation, respectively). In both panels, data are means ± SD (n = 3). Full article ">Figure A1
Crystal structure of wild-type MmPylRS and MmPylRS–tRNAPyl complex (PDB ID 2Q7H and 5UD5). (A) Molecular microenvironment of residue S193 located outside of the active site pocket but in the C-terminal tRNA binding domain. (B) Additional aaRS residues T13, V31, I36, T56, R61, H62, and H63 located in the MmPylRS N-terminal domain and important for activity in vivo. Full article ">

19 pages, 1475 KiB

Open AccessArticle

Novel Harmicines with Improved Potency against Plasmodium

by Marina Marinović, Ivana Perković, Diana Fontinha, Miguel Prudêncio, Jana Held, Lais Pessanha de Carvalho, Tana Tandarić, Robert Vianello, Branka Zorc and Zrinka Rajić

Molecules 2020, 25(19), 4376; https://doi.org/10.3390/molecules25194376 - 23 Sep 2020

Cited by 16 | Viewed by 3744

Abstract

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were [...] Read more.

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 2213 KiB

Open AccessArticle

The Microbiota-Derived Metabolite of Quercetin, 3,4-Dihydroxyphenylacetic Acid Prevents Malignant Transformation and Mitochondrial Dysfunction Induced by Hemin in Colon Cancer and Normal Colon Epithelia Cell Lines

by Mabel Catalán, Jorge Ferreira and Catalina Carrasco-Pozo

Molecules 2020, 25(18), 4138; https://doi.org/10.3390/molecules25184138 - 10 Sep 2020

Cited by 20 | Viewed by 3312

Abstract

Meat diet plays a pivotal role in colorectal cancer (CRC). Hemin, a metabolite of myoglobin, produced after meat intake, has been involved in CRC initiation. The compound, 3,4-dihydroxyphenylacetic acid (3,4HPAA) is a scarcely studied microbiota-derived metabolite of the flavonoid quercetin (QUE), which exert [...] Read more.

Meat diet plays a pivotal role in colorectal cancer (CRC). Hemin, a metabolite of myoglobin, produced after meat intake, has been involved in CRC initiation. The compound, 3,4-dihydroxyphenylacetic acid (3,4HPAA) is a scarcely studied microbiota-derived metabolite of the flavonoid quercetin (QUE), which exert antioxidant properties. The aim of this study was to determine the protective effect of 3,4HPAA against malignant transformation (increased cell proliferation, decreased apoptosis, DNA oxidative damage and augmented reactive oxidative species (ROS) levels) and mitochondrial dysfunction induced by hemin in normal colon epithelial cells and colon cancer cells. The effect of 3,4HPAA was assessed in comparison to its precursor, QUE and to a known CRC protective agent, sulforaphane (SFN). The results showed that both, tumor and normal cells, exposed to hemin, presented increased cell proliferation, decreased caspase 3 activity and cytochrome c release, as well as augmented production of intracellular and mitochondrial ROS. In addition, hemin decreased the mitochondrial membrane potential (MMP) and the activity of complexes I and II of the electron transport chain. These effects of hemin were prevented by the action of 3,4HPAA. The metabolite showed to be more active than QUE and slightly less active than SFN. In conclusion, 3,4HPAA administration could represent a promising strategy for preventing malignant transformation and mitochondrial dysfunction in colon epithelia induced by hemin. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1

Figure 1
Effect of hemin, SFN, QUE and 3,4HPAA in cell viability. (A) RKO cells and (B) CCD841 cells were incubated with increasing concentrations of hemin (0.05–50 μM), SFN, QUE or 3,4HPAA (0.05–200 μM). After 72 h, the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reduction was detected by absorbance (MTS assay). The results were expressed as percentage of inhibition in relation to the positive control (30 µM puromycin) and calculated as: ((OD0.4% DMSO − ODsample) × 100)/(OD0.4% DMSO − ODpuromycin). Values are expressed as mean ± SEM, from three independent culture preparations. 3,4HPAA, 3,4-dihydroxyphenylacetic acid; QUE, quercetin; SFN, sulforaphane. Full article ">Figure 2
Effect of hemin, SFN, QUE and 3,4HPAA in apoptosis. Cells were incubated with vehicle (0.4% DMSO), 1 μM SFN, 10 μM QUE or 2.6 μM 3,4HPAA in the absence or presence of 10 μM hemin. After 72 h, caspase 3 activity was measured in (A) RKO cells and (B) CCD841 cells; as well as cytochrome c levels in the media of (C) RKO cells; and (D) CCD841 cells. Caspase activity and cytochrome c release were expressed as p-nitroanilide/min/mg of protein, and ng (cytochrome c)/mg of protein, respectively. Values are expressed as mean ± SEM, from three independent culture preparations. For all bars with the same letter, the difference between the means is not statistically significant. Values with different letters indicate significant differences (p < 0.05) between bars (two-way ANOVA, Bonferroni post-test). 3,4HPAA, 3,4-dihydroxyphenylacetic acid; QUE, quercetin; SFN, sulforaphane. Full article ">Figure 3
Effect of hemin, SFN, QUE and 3,4HPAA in ROS levels. Cells were incubated with vehicle (0.4% DMSO), 1 μM SFN, 10 μM QUE or 2.6 μM 3,4HPAA in the absence or presence of 10 μM hemin. After 72 h, DCF oxidation was measured by fluorescence in (A) RKO cells; and (B) CCD841 cells; as well as MitoSoxTM Red oxidation in (C) RKO cells; and (D) CCD841 cells. The results were expressed as RFU/mg of protein. Values are expressed as mean ± SEM, from three independent culture preparations. For all bars with the same letter, the difference between the means is not statistically significant. Values with different letters indicate significant differences (p < 0.05) between bars (two-way ANOVA, Bonferroni post-test). 3,4HPAA, 3,4-dihydroxyphenylacetic acid; DCF, dichlorofluorescein; QUE, quercetin; SFN, sulforaphane; RFU, relative fluorescence unit. Full article ">Figure 4
Effect of hemin, SFN, QUE and 3,4HPAA in DNA/RNA damage. Cells were incubated with vehicle (0.4% DMSO), 1 μM SFN, 10 μM QUE or 2.6 μM 3,4HPAA in the absence or presence of 10 μM hemin. After 72 h, 8OHdG and 8OHG levels were assessed in (A) RKO; and (B) CCD841 cell supernatants. The results were expressed as pg (8OHdG and 8OHG)/mg of protein. Values are expressed as mean ± SEM, from three independent culture preparations. For all bars with the same letter, the difference between the means is not statistically significant. Values with different letters indicate significant differences (p < 0.05) between bars (two-way ANOVA, Bonferroni post-test). 3,4HPAA, 3,4-dihydroxyphenylacetic acid; 8OHdG, 8-hydroxy-2′-deoxyguanosine; 8OHG, 8-hydroxyguanosine; QUE, quercetin; SFN, sulforaphane. Full article ">Figure 5
Effect of hemin, SFN, QUE and 3,4HPAA in MMP. Cells were incubated with vehicle (0.4% DMSO), 1 μM SFN, 10 μM QUE or 2.6 μM 3,4HPAA in the absence or presence of 10 μM hemin. After 72 h, MMP was measured by fluorescence in (A) RKO; and (B) CCD841 cell supernatants. Results were expressed as RFU/mg of protein. Values are expressed as mean ± SEM, from three independent culture preparations. For all bars with the same letter, the difference between the means is not statistically significant. The values with different letters indicate significant differences (p < 0.05) between bars (two-way ANOVA, Bonferroni post-test3,4HPAA, 3,4-dihydroxyphenylacetic acid; MMP, mitochondrial membrane potential; QUE, quercetin; SFN, sulforaphane; RFU, relative fluorescence unit. Full article ">Figure 6
Effect of hemin, SFN, QUE and 3,4HPAA in complex I and II activities. Cells were incubated for 72 h with vehicle (0.4% DMSO), 1 μM SFN, 10 μM QUE or 2.6 μM 3,4HPAA in the absence or presence of 10 μM hemin. Complex I activity was measured in (A) RKO cells; and (B) CCD841 cells and results were expressed as nmol of oxidized NADH/minute/mg of protein. Complex II activity was measured in (C) RKO cells; and (D) CCD841 cells and results were expressed as nmol of reduced DCIP/minute/mg of protein. Values are expressed as mean ± SEM, from three independent culture preparations. For all bars with the same letter, the difference between the means is not statistically significant. Values with different letters indicate significant differences (p < 0.05) between bars (two-way ANOVA, Bonferroni post-test). 3,4HPAA, 3,4-dihydroxyphenylacetic acid; DCIP, 2,6-dichlorophenolin-dophenol; QUE, quercetin; SFN, sulforaphane. Full article ">

10 pages, 1165 KiB

Open AccessCommunication

In Vitro Studies on Antioxidant and Anti-Parasitic Activities of Compounds Isolated from Rauvolfia caffra Sond

by Dorcas B. Tlhapi, Isaiah D. I. Ramaite, Chinedu P. Anokwuru, Teunis van Ree and Heinrich C. Hoppe

Molecules 2020, 25(17), 3781; https://doi.org/10.3390/molecules25173781 - 20 Aug 2020

Cited by 7 | Viewed by 2962

Abstract

As part of an ongoing study of natural products from local medicinal plants, the methanol extract of stem bark of Rauvolfia caffra Sond was investigated for biological activity. Column chromatography and preparative thin-layer chromatography were used to isolate lupeol (1), raucaffricine [...] Read more.

As part of an ongoing study of natural products from local medicinal plants, the methanol extract of stem bark of Rauvolfia caffra Sond was investigated for biological activity. Column chromatography and preparative thin-layer chromatography were used to isolate lupeol (1), raucaffricine (2), N-methylsarpagine (3), and spegatrine (4). The crude extract, fractions and isolated compounds were tested for anti-oxidant, antitrypanosomal and anti-proliferation activities. Two fractions displayed high DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity and reducing power with IC₅₀ (The half maximal inhibitory concentration) and IC_0.5 values of 0.022 ± 0.003 mg/mL and 0.036 ± 0.007 mg/mL, and 0.518 ± 0.044 mg/mL and 1.076 ± 0.136 mg/mL, respectively. Spegatrine (4) was identified as the main antioxidant compound in R. caffra with IC₅₀ and IC_0.5 values of 0.119 ± 0.067 mg/mL and 0.712 ± 0 mg/mL, respectively. One fraction displayed high antitrypanosomal activity with an IC₅₀ value of 18.50 μg/mL. However, the major constituent of this fraction, raucaffricine (2), was not active. The crude extract, fractions and pure compounds did not display any cytotoxic effect at a concentration of 50 μg/mL against HeLa cells. This study shows directions for further in vitro studies on the antioxidant and antitrypanosomal activities of Rauvolfia caffra Sond. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 3444 KiB

Open AccessArticle

Unravelling the Antibacterial Activity of Terminalia sericea Root Bark through a Metabolomic Approach

by Chinedu P Anokwuru, Sidonie Tankeu, Sandy van Vuuren, Alvaro Viljoen, Isaiah D. I Ramaite, Orazio Taglialatela-Scafati and Sandra Combrinck

Molecules 2020, 25(16), 3683; https://doi.org/10.3390/molecules25163683 - 13 Aug 2020

Cited by 17 | Viewed by 4237

Abstract

Terminalia sericea Burch. ex. DC. (Combretaceae) is a popular remedy for the treatment of infectious diseases. It is widely prescribed by traditional healers and sold at informal markets and may be a good candidate for commercialisation. For this to be realised, a thorough [...] Read more.

Terminalia sericea Burch. ex. DC. (Combretaceae) is a popular remedy for the treatment of infectious diseases. It is widely prescribed by traditional healers and sold at informal markets and may be a good candidate for commercialisation. For this to be realised, a thorough phytochemical and bioactivity profile is required to identify constituents that may be associated with the antibacterial activity and hence the quality of raw materials and consumer products. The aim of this study was to explore the phytochemistry and identify the antibacterial constituents of T. sericea root bark, using a metabolomic approach. The chemical profiles and antibacterial activities of 42 root bark samples collected from three districts in the Limpopo Province, South Africa, were evaluated. Dichloromethane:methanol (1:1) extracts were analysed using ultraperformance liquid chromatography (UPLC)-mass spectrometry (MS), and chemometric models were constructed from the aligned data. The extracts were tested against Bacillus cereus (ATCC 11778), Staphylococcus epidermidis (ATCC 12223), Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 8739), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (ATCC 27853), Shigella sonnei (ATCC 9292) and Salmonella typhimurium (ATCC 14028), using the minimum inhibition microdilution assay. Nine compounds; sericic acid, sericoside, resveratrol-3-O-β-rutinoside, ellagic acid, flavogallonic acid dilactone, methyl-flavogallonate, quercetin-3-(2′′-galloylrhamnoside), resveratrol-3-(6′′-galloyl)-O-β-d-glucopyranoside and arjunetin, were isolated from the root bark. All the compounds, with the exception of sericic acid, sericoside and resveratrol-3-O-β-rutinoside, were isolated for the first time from the root bark of T. sericea. Chemometric analysis revealed clustering that was not population specific, and the presence of three groupings within the samples, characterised by sericic acid, sericoside and an unidentified compound (m/z 682/4.66 min), respectively. The crude extracts from different populations displayed varied antibacterial activities against S. typhimurium (minimum inhibitory concentrations (MICs) 0.25–1.0 mg/mL), but similar activity towards Bacillus cereus (1.0 mg/mL). Several compounds present in the root bark were highly active towards all or most of the pathogens tested, but this activity was not reflected by the chemical profiles of extracts prepared from the individual samples. Among the pure compounds tested, only flavogallonic acid dilactone and methyl-flavogallonate exhibited broad-spectrum activity. A biochemometric analysis indicated that there was no consistent association between the levels of phytochemicals and the activity of the active or non-active extracts. Although it was deduced that the major constituents of T. sericea root bark contributed to the chemotypic variation, further investigation of the interactions of compounds present in the root bark may provide antibacterial efficacies not evident when examining compounds singularly. The data reported herein will provide information that is fundamentally important for the development of quality control protocols. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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(A) Hierarchical cluster analysis dendrogram of the ultra performance liquid chromatography (UPLC)-mass spectrometry (MS) data (N = 39) obtained from Waterberg, Mopani and Vhembe districts of Limpopo Province. Branch X (red): samples from Waterberg and Mopani; branch Y (green): samples from Waterberg and Vhembe; branch Z (blue): samples from Mopani and Vhembe districts. (B) Partial least square discriminant analysis (PLS-DA) of clusters from the dendrogram. (C) Loadings scores plot obtained from the PLS-DA analysis. Compound indicated by red rectangle contributed to the clustering of the Red (X) group, while compound in blue rectangle contributed to the clustering of the Blue group (Z). These two compounds are the first two variables indicated by the variable importance for project (VIP) plot. Full article ">Figure 2
Compounds (1–9) isolated from dichloromethane:methanol crude extract of T. sericea root bark. Full article ">Figure 3
S-plot indicating biomarkers (retention time/molecular ion m/z) for the activity against S. typhi. Full article ">Figure 4
Heatmap of 15 VIP peaks in 39 samples of T. sericea root bark tested against S. typhi. R-3-O-R: resveratrol-3-O-β-rutinoside. Full article ">Figure 5
UPLC-MS chromatogram of dichloromethane:methanol crude extract of T. sericea root bark indicating bioactive compounds and chemical markers. Full article ">

15 pages, 2047 KiB

Open AccessArticle

Veronica austriaca L. Extract and Arbutin Expand Mature Double TNF-α/IFN-γ Neutrophils in Murine Bone Marrow Pool

by Petya A. Dimitrova, Kalina Alipieva, Tsvetinka Grozdanova, Milena Leseva, Dessislava Gerginova, Svetlana Simova, Andrey S. Marchev, Vassya Bankova, Milen I. Georgiev and Milena P. Popova

Molecules 2020, 25(15), 3410; https://doi.org/10.3390/molecules25153410 - 28 Jul 2020

Cited by 3 | Viewed by 2946

Abstract

Plants from the Veronica genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated Veronica austriaca L., collected from two habitats in Bulgaria—the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), [...] Read more.

Plants from the Veronica genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated Veronica austriaca L., collected from two habitats in Bulgaria—the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), were analyzed by nuclear magnetic resonance (NMR) spectroscopy. The secondary metabolite, arbutin, was identified as a major constituent in both extracts, and further quantified by high-performance liquid chromatography (HPLC), while catalpol, aucubin and verbascoside were detected at lower amounts. The effect of the extracts and of pure arbutin on the survival of neutrophils isolated from murine bone marrow (BM) were determined by colorimetric assay. The production of cytokines—tumor necrosis factor (TNF)-α and interferon (IFN)-γ was evaluated by flowcytometry. While Vau-1 inhibited neutrophil vitality in a dose-dependent manner, arbutin stimulated the survival of neutrophils at lower concentrations, and inhibited cell density at higher concentrations. The Vau-1 increased the level of intracellular TNF-α, while Vau-2 and arbutin failed to do so, and expanded the frequency of mature double TNF-α⁺/IFN-γ^hi neutrophils within the BM pool. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1
1H NMR spectra of Vau-1 (blue), pure arbutin (red) and Vau-2 (green). Full article ">Figure 2
Effect of the Vau-1/Vau-2 extracts or arbutin on neutrophil vitality and survival. (A) Chemical structure of arbutin; (B) Vitality of bone marrow (BM)-derived neutrophils compared to control cultures. Vitality was calculated as a percentage of control cultures containing cells only. Data represent mean ± SD of cell samples isolated from 7 mice and plated in triplicate. P values are shown for each group when compared to control; (C) Dose-dependent effect of Vau-1 on DMSO-induced survival of BM-derived neutrophils. Data represent mean ± SD of sample isolated and pooled from 7 mice and run in triplicate. Red line shows the survival (relative value) at DMSO-treated group. Black line is the polygonal trend line drawn to extrapolate the vitality vs. Vau-1 extract concentration; (D) Dose-dependent effect of arbutin on DMSO-induced survival of BM-derived neutrophils. Data represent mean ± SD of samples isolated from 7 mice and plated in triplicate. Red line shows the survival (relative value) at DMSO-treated group. Black line is the polygonal trend line drawn to extrapolate the vitality vs. the arbutin concentrations. Full article ">Figure 3
Effect of Vau-1/Vau-2 or arbutin on production of cytokines IFN-γ (A) and TNF-α (B). Purified neutrophils were cultured in the presence of DMSO (0.3%) and decreasing concentrations of Vau-1, Vau-2 and arbutin for 36 h. Control cells were incubated with phosphate-buffered saline (cells). In the last 4 h of incubation, the neutrophils were stimulated with PMA/Yon in the presence of the Golgi inhibitor, monensim, in order to maximize cytokine accumulation. The neutrophils were then washed and stained for the neutrophil marker, Ly6G. The cells were then fixed, permeabilized and incubated with PE/Cy7 or APC/Cy7 conjugated antibodies against TNF-α and IFN-γ. After washing, gated Ly6G+ cells were subjected to flow cytometry analysis for the intracellular production of cytokines. Data represent mean ± SD of sample from 2 experiments with neutrophils isolated and pooled from 7 mice and assayed in duplicate. P-values are shown for each group when compared to the group cultured with 0.3% DMSO; * p < 0.05; ** p < 0.01; *** p < 0.001, two-tailed Student t-test. Full article ">Figure 4
Effect of Vau-1/Vau-2 extracts or arbutin on proportion of neutrophils at various maturation states. (A) Gating strategy for neutrophils. The first panel shows the histogram for Ly6G expression and gating of Ly6G+ positive cells. The second panel shows the dot-plot histogram with scales for Ly6G+ cells vs. SSC-A (the size surface volume), that determines the shape and granularity of the BM-derived neutrophils. The following populations were defined on the basis of SSC-A and Ly6G positivity (staining with fluorescein isothiocyanate (FITC)-labelled antibody against Ly6G). Upper Left (P1 gate)—SSChiLy6Glow immature transient cells; Upper right (P2 gate)—SSChiLy6Ghi mature cells; Lower left (P3 gate)—SSClowLy6Glow immature cells; Lower right (P4 gate)—SSClowLy6Ghi mature transient cells; (B) Proportion of neutrophils at various maturation states in BM cells incubated in the presence or absence of Vau-1, Vau-2 or arbutin for 36 h. Data represent mean ± SD of sample from 2 experiments with neutrophils isolated and pooled from 7 mice and assayed in duplicate. Full article ">Figure 5
Effect of Vau-1/Vau-2 extracts or arbutin on the frequency of double TNF-α+/IFN-γ+ producers within the pool of immature and mature neutrophils in BM. (A) Representative dot-plot histograms showing two populations of double TNF-α+/IFN-γ+ producers in the control group: TNF-α+/IFN-γlow and TNF-α+/IFN-γhi which varied in frequency in immature, mature or transient immature or mature pools; (B) Proportion of TNF-α+/IFN-γlow neutrophils (in %) at various maturation state in BM cell cultures incubated in the presence or absence of Vau-1, Vau-2 or arbutin for 36 h. Data represent mean ± SD of sample from 2 experiments with neutrophils isolated and pooled from 7 mice and assayed in triplicate; (C) Proportion of TNF-α+/IFN-γhi neutrophils (in %) at various maturation state in BM cell cultures incubated in the presence or absence of Vau-1, Vau-2 or arbutin for 36 h. Data represent mean ± SD of sample from 2 experiments, with neutrophils isolated and pooled from 7 mice and assayed in triplicate. Full article ">

Review

Jump to: Research

19 pages, 969 KiB

Open AccessReview

Immunomodulatory, Anti-Inflammatory, and Anti-Cancer Properties of Ginseng: A Pharmacological Update

by Jose Antonio Valdés-González, Marta Sánchez, Ignacio Moratilla-Rivera, Irene Iglesias and María Pilar Gómez-Serranillos

Molecules 2023, 28(9), 3863; https://doi.org/10.3390/molecules28093863 - 3 May 2023

Cited by 20 | Viewed by 5851

Abstract

Ginseng, a medicinal plant of the genus Panax, boasts a rich historical record of usage that dates back to the Paleolithic period. This botanical is extensively acknowledged and consumed in Eastern countries for its therapeutic properties, and, in Western countries, it is [...] Read more.

Ginseng, a medicinal plant of the genus Panax, boasts a rich historical record of usage that dates back to the Paleolithic period. This botanical is extensively acknowledged and consumed in Eastern countries for its therapeutic properties, and, in Western countries, it is becoming increasingly popular as a remedy for fatigue and asthenia. This review provides an update on current research pertaining to ginseng and its isolated compounds, namely, ginsenosides and polysaccharides. The primary focus is on three crucial pharmacological activities, namely, immunomodulation, anti-inflammatory, and anti-cancer effects. The review encompasses studies on both isolated compounds and various ginseng extracts obtained from the root, leaves, and berries. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 2523 KiB

Open AccessReview

Recent Developments in the Biological Activities, Bioproduction, and Applications of Pseudomonas spp. Phenazines

by Bruno Serafim, Ana R. Bernardino, Filomena Freitas and Cristiana A. V. Torres

Molecules 2023, 28(3), 1368; https://doi.org/10.3390/molecules28031368 - 1 Feb 2023

Cited by 23 | Viewed by 4321

Abstract

Phenazines are a large group of heterocyclic nitrogen-containing compounds with demonstrated insecticidal, antimicrobial, antiparasitic, and anticancer activities. These natural compounds are synthesized by several microorganisms originating from diverse habitats, including marine and terrestrial sources. The most well-studied producers belong to the Pseudomonas genus, [...] Read more.

Phenazines are a large group of heterocyclic nitrogen-containing compounds with demonstrated insecticidal, antimicrobial, antiparasitic, and anticancer activities. These natural compounds are synthesized by several microorganisms originating from diverse habitats, including marine and terrestrial sources. The most well-studied producers belong to the Pseudomonas genus, which has been extensively investigated over the years for its ability to synthesize phenazines. This review is focused on the research performed on pseudomonads’ phenazines in recent years. Their biosynthetic pathways, mechanism of regulation, production processes, bioactivities, and applications are revised in this manuscript. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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On agar plate, strains: P. chlororaphis 30-84 wildtype (WT), phenazine non-producer (ZN), PCA only producer (PCA), and 2-OH-PCA overproducer (O*) [<a href="#B18-molecules-28-01368" class="html-bibr">18</a>]. Full article ">Figure 2
Phenazine production on a bioreactor cultivation of Pseudomonas chlororaphis subsp. aurantiaca DSM 19603. Full article ">Figure 3
Biosynthetic pathway for phenazine production by Pseudomonas spp. DAHP: 3-deoxy-d-arabino-heptulosonate 7-phosphate; ADIC: 2-amino-2-deoxyisochorismate; DHHA: trans 2,3-dihydro-3-hydroxyanthranilic acid; AOCHC: 6-amino-5-oxocyclohex-2-ene-1-carboxylic acid; HHPDC: hexahydro-phenazine-1,6-dicarboxylate; PHZ: phenazines; PDC: phenazine-1,6-dicarboxylic acid; PCA: 4 phenazine-1-carboxylic acid; 1-OH-PHZ: 2 1-hydroxy-phenazine; PCN: 5 phenazine-1-carboxamide; 2-OH-PHZ: 3 2-hydroxy-phenazine; 5-MPCA: 5-methylphenazine 1-carboxylato; PYO: 1 pyocianin. Full article ">Figure 4
Quorum-sensing regulation mechanism. Full article ">Figure 5
Spectra of different characterization analyses of phenazines, (A) Phase-reverse HPLC chromatogram of PCA and PCN [<a href="#B49-molecules-28-01368" class="html-bibr">49</a>]; (B) PCA and PCN peaks detected by LC-MS [<a href="#B18-molecules-28-01368" class="html-bibr">18</a>]; (C) FTIR spectrum of crystalline PCA [<a href="#B76-molecules-28-01368" class="html-bibr">76</a>]. Full article ">Figure 6
Spectra of PCN phenazine by (A) 1H NMR and by (B) 13C NMR [<a href="#B12-molecules-28-01368" class="html-bibr">12</a>]. Full article ">

13 pages, 1337 KiB

Open AccessReview

Tyrosinase Inhibitors Naturally Present in Plants and Synthetic Modifications of These Natural Products as Anti-Melanogenic Agents: A Review

by Mubashir Hassan, Saba Shahzadi and Andrzej Kloczkowski

Molecules 2023, 28(1), 378; https://doi.org/10.3390/molecules28010378 - 2 Jan 2023

Cited by 33 | Viewed by 8114

Abstract

Tyrosinase is a key enzyme target to design new chemical ligands against melanogenesis. In the current review, different chemical derivatives are explored which have been used as anti-melanogenic compounds. These are different chemical compounds naturally present in plants and semi-synthetic and synthetic compounds [...] Read more.

Tyrosinase is a key enzyme target to design new chemical ligands against melanogenesis. In the current review, different chemical derivatives are explored which have been used as anti-melanogenic compounds. These are different chemical compounds naturally present in plants and semi-synthetic and synthetic compounds inspired by these natural products, such as kojic acid produced by several species of fungi; arbutin—a glycosylated hydroquinone extracted from the bearberry plant; vanillin—a phenolic aldehyde extracted from the vanilla bean, etc. After enzyme inhibition screening, various chemical compounds showed different therapeutic effects as tyrosinase inhibitors with different values of the inhibition constant and IC₅₀. We show how appropriately designed scaffolds inspired by the structures of natural compounds are used to develop novel synthetic inhibitors. We review the results of numerous studies, which could lead to the development of effective anti-tyrosinase agents with increased efficiency and safety in the near future, with many applications in the food, pharmaceutical and cosmetics industries. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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29 pages, 7199 KiB

Open AccessReview

Ursolic Acid Analogs as Potential Therapeutics for Cancer

by Siva S. Panda, Muthusamy Thangaraju and Bal L. Lokeshwar

Molecules 2022, 27(24), 8981; https://doi.org/10.3390/molecules27248981 - 16 Dec 2022

Cited by 29 | Viewed by 3841

Abstract

Ursolic acid (UA) is a pentacyclic triterpene isolated from a large variety of vegetables, fruits and many traditional medicinal plants. It is a structural isomer of Oleanolic Acid. The medicinal application of UA has been explored extensively over the last two decades. The [...] Read more.

Ursolic acid (UA) is a pentacyclic triterpene isolated from a large variety of vegetables, fruits and many traditional medicinal plants. It is a structural isomer of Oleanolic Acid. The medicinal application of UA has been explored extensively over the last two decades. The diverse pharmacological properties of UA include anti-inflammatory, antimicrobial, antiviral, antioxidant, anti-proliferative, etc. Especially, UA holds a promising position, potentially, as a cancer preventive and therapeutic agent due to its relatively non-toxic properties against normal cells but its antioxidant and antiproliferative activities against cancer cells. Cell culture studies have shown interference of UA with multiple pharmacological and molecular targets that play a critical role in many cells signaling pathways. Although UA is considered a privileged natural product, its clinical applications are limited due to its low absorption through the gastro-intestinal track and rapid elimination. The low bioavailability of UA limits its use as a therapeutic drug. To overcome these drawbacks and utilize the importance of the scaffold, many researchers have been engaged in designing and developing synthetic analogs of UA via structural modifications. This present review summarizes the synthetic UA analogs and their cytotoxic antiproliferative properties reported in the last two decades. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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24 pages, 1607 KiB

Open AccessReview

Effects of Berberine against Pancreatitis and Pancreatic Cancer

by Filip Vlavcheski, Eric J. O’Neill, Filip Gagacev and Evangelia Tsiani

Molecules 2022, 27(23), 8630; https://doi.org/10.3390/molecules27238630 - 6 Dec 2022

Cited by 14 | Viewed by 8788

Abstract

The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused [...] Read more.

The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world’s most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Figure 1
Mechanism of pancreatic acinar cell death induced by pancreatitis. In pancreatic cells, alcohol, cholecystokinin (CCK) and bile acids lead to activation of inositol 1,4,5-trisphosphate receptor (Ins (1,4,5) P3R) in the endoplasmic reticulum (ER) (1) which results in calcium release into the cytosol (2). The resulting low calcium concentration in the ER triggers opening of calcium release-activated calcium channel protein 1 (ORAL1), which allows extracellular calcium to enter the cell (3). This results in pathological global calcium concentration elevation within the pancreatic cells. Additionally, the calcium elevation results in the opening of mitochondrial permeability transition pores (MPTPs) (4) triggering a high conductive state and loss of mitochondrial membrane potential and depletion of ATP (5) leading to mitochondrial dysfunction and necrosis (6). The ATP reductions then inhibit the activity of the SERCA pump preventing the storage of excess cytosolic calcium ions in the ER (7). These events lead to early trypsinogen activation, NFκB activation, production of pro-inflammatory cytokines, impaired autophagy, and major dysfunction resulting in cell death (8). Full article ">Figure 2
Cell signalling pathways disrupted in pancreatic intraepithelial neoplasia (PanIN). Pancreatic intraepithelial neoplasia is characterized by inactivating mutations in tumour suppressor CDKN2A and CDKN1A, encoding p16 and p21, leading to increased progression from G1 into S-phase of the cell cycle. Additionally, more than 90% of lesions have constitutively active KRAS mutations leading to overactivation of RAF-MEK-ERK and PI3K-AKT-mTOR signalling, resulting in enhanced proliferation and survival. Furthermore, PanIN interrupts downstream TGFβ signalling through SMAD4 inhibition leading to decreased apoptosis and cytostasis. Lastly, PanIN frequently results in loss-of-function mutations in the TP53 gene encoding the tumour suppressor p53. Full article ">Figure 3
Chemical structure and sources of naturally occurring berberine (C20H18NO4+). Full article ">Figure 4
Different routes of Berberine administration. Common routes of BBR administration include oral, intragastric (IG), intraperitoneal (IP), and intravenous (IV). Full article ">Figure 5
Summary of the effects of berberine in pancreatic cancer cells. Berberine (BBR) was shown to restore p16 and p21 function in pancreatic intraepithelial neoplasia (PanIN). BBR increased AMP-activated protein kinase (AMPK) and apoptosis signalling and decreased oncogenic Kirsten rat sarcoma virus (KRAS), extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase (p70S6K) signalling, culminating in decreased proliferation and survival, and increased apoptosis, cytostasis, and autophagy. Full article ">

16 pages, 1126 KiB

Open AccessReview

The Antioxidative Effects of Picein and Its Neuroprotective Potential: A Review of the Literature

by Leila Elyasi, Jessica M. Rosenholm, Fatemeh Jesmi and Mehrdad Jahanshahi

Molecules 2022, 27(19), 6189; https://doi.org/10.3390/molecules27196189 - 21 Sep 2022

Cited by 4 | Viewed by 2882

Abstract

Neurodegenerative diseases (NDDs) are the main cause of dementia in the elderly, having no cure to date, as the currently available therapies focus on symptom remission. Most NDDs will progress despite treatment and eventually result in the death of the patient after several [...] Read more.

Neurodegenerative diseases (NDDs) are the main cause of dementia in the elderly, having no cure to date, as the currently available therapies focus on symptom remission. Most NDDs will progress despite treatment and eventually result in the death of the patient after several years of a burden on both the patient and the caregivers. Therefore, it is necessary to investigate agents that tackle the disease pathogenesis and can efficiently slow down or halt disease progression, with the hope of curing the patients and preventing further burden and mortality. Accordingly, recent research has focused on disease-modifying treatments with neuroregenerative or neuroprotective effects. For this purpose, it is necessary to understand the pathogenesis of NDDs. It has been shown that oxidative stress plays an important role in the damage to the central nervous system and the progression of neurodegenerative disorders. Furthermore, mitochondrial dysfunction and the accumulation of unfolded proteins, including beta-amyloid (Aβ), tau proteins, and α-synuclein, have been suggested. Accordingly, cellular and molecular studies have investigated the efficacy of several natural compounds (herbs and nutritional agents) for their neuroprotective and antioxidative properties. The most popular herbs suggested for the treatment and/or prevention of NDDs include Withania somnifera (ashwagandha), ginseng, curcumin, resveratrol, Baccopa monnieri, and Ginkgo biloba. In some herbs, such as ginseng, preclinical and clinical evidence are available for supporting its effectiveness; however, in some others, only cellular and animal studies are available. In line with the scant literature in terms of the effectiveness of herbal compounds on NDDs, there are also other herbal agents that have been disregarded. Picein is one of the herbal agents that has been investigated in only a few studies. Picein is the active ingredient of several herbs and can be thus extracted from different types of herbs, which makes it more available. It has shown to have anti-inflammatory properties in cellular and plant studies; however, to date, only one study has suggested its neuroprotective properties. Furthermore, some cellular studies have shown no anti-inflammatory effect of picein. Therefore, a review of the available literature is required to summarize the results of studies on picein. To date, no review study seems to have addressed this issue. Thus, in the present study, we gather the available information about the antioxidative and potential neuroprotective properties of picein and its possible effectiveness in treating NDDs. We also summarize the plants from which picein can be extracted in order to guide researchers for future investigations. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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24 pages, 4244 KiB

Open AccessReview

A Comprehensive View on the Quercetin Impact on Colorectal Cancer

by Andreea-Adriana Neamtu, Teodor-Andrei Maghiar, Amina Alaya, Neli-Kinga Olah, Violeta Turcus, Diana Pelea, Bogdan Dan Totolici, Carmen Neamtu, Adrian Marius Maghiar and Endre Mathe

Molecules 2022, 27(6), 1873; https://doi.org/10.3390/molecules27061873 - 14 Mar 2022

Cited by 37 | Viewed by 6623

Abstract

Colorectal cancer (CRC) represents the third type of cancer in incidence and second in mortality worldwide, with the newly diagnosed case number on the rise. Among the diagnosed patients, approximately 70% have no hereditary germ-line mutations or family history of pathology, thus being [...] Read more.

Colorectal cancer (CRC) represents the third type of cancer in incidence and second in mortality worldwide, with the newly diagnosed case number on the rise. Among the diagnosed patients, approximately 70% have no hereditary germ-line mutations or family history of pathology, thus being termed sporadic CRC. Diet and environmental factors are to date considered solely responsible for the development of sporadic CRC; therefore; attention should be directed towards the discovery of preventative actions to combat the CRC initiation, promotion, and progression. Quercetin is a polyphenolic flavonoid plant secondary metabolite with a well-characterized antioxidant activity. It has been extensively reported as an anti-carcinogenic agent in the scientific literature, and the modulated targets of quercetin have been also characterized in the context of CRC, mainly in original research publications. In this fairly comprehensive review, we summarize the molecular targets of quercetin reported to date in in vivo and in vitro CRC models, while also giving background information about the signal transduction pathways that it up- and downregulates. Among the most relevant modulated pathways, the Wnt/β-catenin, PI3K/AKT, MAPK/Erk, JNK, or p38, p53, and NF-κB have been described. With this work, we hope to encourage further quests in the elucidation of quercetin anti-carcinogenic activity as single agent, as dietary component, or as pharmaconutrient delivered in the form of plant extracts. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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31 pages, 24342 KiB

Open AccessReview

Zingiber officinale var. rubrum: Red Ginger’s Medicinal Uses

by Shiming Zhang, Xuefang Kou, Hui Zhao, Kit-Kay Mak, Madhu Katyayani Balijepalli and Mallikarjuna Rao Pichika

Molecules 2022, 27(3), 775; https://doi.org/10.3390/molecules27030775 - 25 Jan 2022

Cited by 48 | Viewed by 12209

Abstract

Zingiber officinale var. rubrum (red ginger) is widely used in traditional medicine in Asia. Unlike other gingers, it is not used as a spice in cuisines. To date, a total of 169 chemical constituents have been reported from red ginger. The constituents include [...] Read more.

Zingiber officinale var. rubrum (red ginger) is widely used in traditional medicine in Asia. Unlike other gingers, it is not used as a spice in cuisines. To date, a total of 169 chemical constituents have been reported from red ginger. The constituents include vanilloids, monoterpenes, sesquiterpenes, diterpenes, flavonoids, amino acids, etc. Red ginger has many therapeutic roles in various diseases, including inflammatory diseases, vomiting, rubella, atherosclerosis, tuberculosis, growth disorders, and cancer. Scientific evidence suggests that red ginger exhibits immunomodulatory, antihypertensive, antihyperlipidemic, antihyperuricemic, antimicrobial, and cytotoxic activities. These biological activities are the underlying causes of red ginger’s therapeutic benefits. In addition, there have been few reports on adverse side effects of red ginger. This review aims to provide insights in terms the bioactive constituents and their biosynthesis, biological activities, molecular mechanisms, pharmacokinetics, and qualitative and quantitative analysis of red ginger. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Photographs of (A) Red ginger (Zingiber officinale var. rubrum), (B) common ginger, and (C) whole plant of Zingiber officinale var. rubrum. Full article ">Figure 2
Biosynthetic scheme of ginger pungent compounds [<a href="#B28-molecules-27-00775" class="html-bibr">28</a>,<a href="#B29-molecules-27-00775" class="html-bibr">29</a>]. The enzymes involved in the biosynthetic pathway to gingerols in ginger are as follows: PAL = Phenylalanine ammonialyase; C4H = cinnamate 4-hydroxylase; 4CL = 4-coumarate: CoA ligase; CST = p-coumaroyl shikimate transferase; CS3H = p-coumaroyl 5-O-shikimate 3-hydroxylase; OMT = O-methyltransferase; CCOMT = caffeoyl-CoA O-methyltransferase. Full article ">Figure 3
Red ginger inhibits cancer progression, angiogenesis, and metastasis [<a href="#B88-molecules-27-00775" class="html-bibr">88</a>]. Full article ">Figure 4
The molecular mechanisms involved in anticancer activity (↓ = downregulation/inhibition, ↑ = upregulation). Full article ">Figure 5
The mechanism of action or red ginger in antihyperlipidemic, antihypertensive, and antihypercholesterolemic activities. Full article ">

37 pages, 508 KiB

Open AccessReview

An Update on Phytochemicals and Pharmacological Activities of the Genus Persicaria and Polygonum

by Gisela Seimandi, Norma Álvarez, María Inés Stegmayer, Laura Fernández, Verónica Ruiz, María Alejandra Favaro and Marcos Derita

Molecules 2021, 26(19), 5956; https://doi.org/10.3390/molecules26195956 - 1 Oct 2021

Cited by 24 | Viewed by 6062

Abstract

The discovery of new pharmaceutical identities, particularly anti-infective agents, represents an urgent need due to the increase in immunocompromised patients and the ineffectiveness/toxicity of the drugs currently used. The scientific community has recognized in the last decades the importance of the plant kingdom [...] Read more.

The discovery of new pharmaceutical identities, particularly anti-infective agents, represents an urgent need due to the increase in immunocompromised patients and the ineffectiveness/toxicity of the drugs currently used. The scientific community has recognized in the last decades the importance of the plant kingdom as a huge source of novel molecules which could act against different type of infections or illness. However, the great diversity of plant species makes it difficult to select them with probabilities of success, adding to the fact that existing information is difficult to find, it is atomized or disordered. Persicaria and Polygonum constitute two of the main representatives of the Polygonaceae family, which have been extensively used in traditional medicine worldwide. Important and structurally diverse bioactive compounds have been isolated from these genera of wild plants; among them, sesquiterpenes and flavonoids should be remarked. In this article, we firstly mention all the species reported with pharmacological use and their geographical distribution. Moreover, a number of tables which summarize an update detailing the type of natural product (extract or isolated compound), applied doses, displayed bioassays and the results obtained for the main bioactivities of these genera cited in the literature during the past 40 years. Antimicrobial, antioxidant, analgesic and anti-inflammatory, antinociceptive, anticancer, antiviral, antiparasitic, anti-diabetic, antipyretic, hepatoprotective, diuretic, gastroprotective and neuropharmacological activities were explored and reviewed in this work, concluding that both genera could be the source for upcoming molecules to treat different human diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

20 pages, 2735 KiB

Open AccessReview

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

by Jan Škubník, Jiří Bejček, Vladimíra Svobodová Pavlíčková and Silvie Rimpelová

Molecules 2021, 26(18), 5627; https://doi.org/10.3390/molecules26185627 - 16 Sep 2021

Cited by 15 | Viewed by 4487

Abstract

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for [...] Read more.

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Chemical structures of cardenolide ouabain (1), bufadienolide bufalin (2), digitoxigenin (3) and its derivative rostafuroxin (4), digoxin (5), oleandrin (6), lanatoside C (7), strophanthidin (8), digitoxin (9), convallatoxin (10), digoxigenin (11), cinobufagin (12), a semisynthetic cardenolide RIDK-34 (13), glucoevatromonoside (14), evomonoside (15), C10 (16), and C11 (17). Compound 1 has a five-membered lactone ring (in red) and compound 2 has a six-membered lactone ring (in blue). Full article ">Figure 2
The life cycle of non-enveloped DNA and enveloped RNA viruses excluding retroviruses. (1) Life cycle of non-enveloped DNA viruses: a virus attaches to a specific cell surface receptor and enters the host cell. Subsequently, the virus exposes its DNA, which is transported to the cell nucleus and is replicated. Next, the DNA is transcribed into RNA followed by translation to viral proteins, which are then post-transcriptionally modified. The viral proteins and replicated DNA assemble into novel viral particles, which are then released from the host cells via disruption of the cell plasma membrane. (2) Life cycle of enveloped RNA viruses: a virus attaches to a specific cell surface receptor and enters the host cell (not indicated in the scheme) or inserts the RNA through the plasma membrane (indicated). This RNA is replicated via viral RNA synthetase and viral proteins are translated and post-transcriptionally modified. Next, the viral particles are released via exocytosis and are enveloped by the plasma membrane containing glycoproteins on its surface. Full article ">Figure 3
Molecular pathways triggered by binding of cardiac glycosides (CGs) to the α-subunit of Na+/K+-ATPase (NKA), which are involved in blocking the viral entry into host cells. By CG binding to NKA, conformational changes of its α-subunit trigger non-receptor tyrosine kinase (Src) to phosphorylate the epidermal growth factor receptor (EGFR). This leads to activation of Src homology 2 domain-containing transforming protein (Shc)/growth factor receptor-bound protein 2 (Grb2)/son of sevenless protein (Sos)/rat sarcoma protein (Ras) pathway. Ras further activates the serine/threonine kinase (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, which triggers reactive oxygen species (ROS) production activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and thereby affects the expression of genes in the nucleus and cell proliferation. The cell proliferation is affected also by protein kinase C (PKC), which activates transcription factors, such as AP1. PKC itself is activated either via the Ras/Raf/MEK/ERK pathway or by Ca2+ ions. The levels of Ca2+ can be elevated by another NKA-based pathway, the phospholipase C (PLC)/inositol triphosphate (IP3)/phosphatidylinositol-3 kinase (PI3K). The latter enzyme is responsible for the transformation of phosphatidylinositol-2-phosphate (PIP2) into phosphatidylinositol-3-phosphate. The PLC/IP3/PI3K pathway is responsible also for blocking the viral entry into cells, however, the exact mechanism of this process has been unclear, so far. The only involvement of 3-phosphoinositide-dependent protein kinase 1 (PDK1) has been proven. This enzyme physiologically activates protein kinase B (Akt), which then enters the cell nucleus and affects gene transcription. Besides, the viral entry into the host cells is blocked directly by Src, also with an unknown mechanism. Full article ">Figure 4
The effect of cardiac glycosides (CGs) on viral RNA synthesis and processing, and protein translation. CGs block RNA splicing by further unexplained mechanisms, which are likely linked to the Na+/K+-ATPase (NKA) signaling function (not indicated in the scheme). The result of this is a decreased pool of viral messenger ribonucleic acids (mRNAs) and a subsequent block of viral protein synthesis. The translation of viral proteins is hampered also by blocking the pumping function of NKA. As a consequence of this, the intracellular level of K+ ions is decreased, which negatively affects ribosomal function. K+ ions play a physiologically important role in the stabilization of the ribosomal complex. The improper function of ribosomes caused by K+ depletion leads to decreased translation of viral proteins. Full article ">

21 pages, 1910 KiB

Open AccessReview

Plants Used for the Traditional Management of Cancer in the Eastern Cape Province of South Africa: A Review of Ethnobotanical Surveys, Ethnopharmacological Studies and Active Phytochemicals

by Idowu Jonas Sagbo and Wilfred Otang-Mbeng

Molecules 2021, 26(15), 4639; https://doi.org/10.3390/molecules26154639 - 30 Jul 2021

Cited by 25 | Viewed by 6035

Abstract

Cancer occurrence is rapidly increasing all over the world, including in developing countries. The current trend in cancer management requires the use of herbal remedies since the majority of anticancer drugs are known to be costly, with unwanted side effects. In the Eastern [...] Read more.

Cancer occurrence is rapidly increasing all over the world, including in developing countries. The current trend in cancer management requires the use of herbal remedies since the majority of anticancer drugs are known to be costly, with unwanted side effects. In the Eastern Cape province, the use of medicinal plants for cancer management has been climbing steadily over the past two decades due to their cultural belief, low cost, efficacy, and safety claims. With the aim of identifying some potential anticancer plants for probable drug development, this study was undertaken to review plants reported by ethnobotanical surveys in the Eastern Cape province of South Africa for the traditional management of cancer. Information regarding plants used for cancer management in the Eastern Cape province was obtained from multidisciplinary databases and ethnobotanical books. About 24 plant species belonging to twenty families have been reported to be used for the traditional management of cancer in the Eastern Cape province. Among the anticancer plant species, only 16 species have been explored scientifically for their anticancer activities. This review authenticated the use of anticancer plant species in the Eastern Cape province and, therefore, identified several promising unexplored species for further scientific evaluation. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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30 pages, 5187 KiB

Open AccessReview

Biosynthesis of Nature-Inspired Unnatural Cannabinoids

by Kevin J. H. Lim, Yan Ping Lim, Yossa D. Hartono, Maybelle K. Go, Hao Fan and Wen Shan Yew

Molecules 2021, 26(10), 2914; https://doi.org/10.3390/molecules26102914 - 14 May 2021

Cited by 12 | Viewed by 9902

Abstract

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for [...] Read more.

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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20 pages, 3436 KiB

Open AccessReview

Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models

by Sun Young Moon, Kwang Dong Kim, Jiyun Yoo, Jeong-Hyung Lee and Cheol Hwangbo

Molecules 2021, 26(9), 2824; https://doi.org/10.3390/molecules26092824 - 10 May 2021

Cited by 23 | Viewed by 8525

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through [...] Read more.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways. Several small molecules inhibiting JAK have been used in clinical trials, and one of them has been approved for IBD treatment. Many anti-inflammatory phytochemicals have been shown to have potential as new drugs for IBD treatment. This review describes the significance of the JAK–STAT pathway as a current therapeutic target for IBD and discusses the recent findings that phytochemicals can ameliorate disease symptoms by affecting the JAK–STAT pathway in vivo in IBD disease models. Thus, we suggest that phytochemicals modulating JAK–STAT pathways are potential candidates for developing new therapeutic drugs, alternative medicines, and nutraceutical agents for the treatment of IBD. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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19 pages, 1472 KiB

Open AccessReview

Pulse Probiotic Superfood as Iron Status Improvement Agent in Active Women—A Review

by Yolanda Victoria Rajagukguk, Marcellus Arnold and Anna Gramza-Michałowska

Molecules 2021, 26(8), 2121; https://doi.org/10.3390/molecules26082121 - 7 Apr 2021

Cited by 7 | Viewed by 4976

Abstract

Active women or women of reproductive age (15–49 years old) have a high risk of suffering from anaemia. Anaemia is not solely caused by iron deficiency, however, the approaches to improve iron status in both cases are greatly related. Improving the iron status [...] Read more.

Active women or women of reproductive age (15–49 years old) have a high risk of suffering from anaemia. Anaemia is not solely caused by iron deficiency, however, the approaches to improve iron status in both cases are greatly related. Improving the iron status of active women can be done by dietary intervention with functional food. This review aims to provide insights about the functional food role to increase iron absorption in active women and the potency of pulse probiotic superfood development in dry matrices. Results showed that the beneficial effect of iron status is significantly improved by the synergic work between probiotic and prebiotic. Furthermore, chickpeas and lentils are good sources of prebiotic and the consumption of pulses are related with 21st century people’s intention to eat healthy food. There are wide possibilities to develop functional food products incorporated with probiotics to improve iron status in active woman. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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25 pages, 4642 KiB

Open AccessReview

Na⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

by Jiří Bejček, Vojtěch Spiwok, Eva Kmoníčková and Silvie Rimpelová

Molecules 2021, 26(7), 1905; https://doi.org/10.3390/molecules26071905 - 28 Mar 2021

Cited by 51 | Viewed by 7932

Abstract

Maintenance of Na⁺ and K⁺ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung [...] Read more.

Maintenance of Na⁺ and K⁺ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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18 pages, 1506 KiB

Open AccessReview

Postbiotics, Metabolic Signaling, and Cancer

by Nikola Vrzáčková, Tomáš Ruml and Jaroslav Zelenka

Molecules 2021, 26(6), 1528; https://doi.org/10.3390/molecules26061528 - 11 Mar 2021

Cited by 24 | Viewed by 6092

Abstract

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and [...] Read more.

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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14 pages, 7269 KiB

Open AccessReview

A Review of Bacteriochlorophyllides: Chemical Structures and Applications

by Chih-Hui Yang, Keng-Shiang Huang, Yi-Ting Wang and Jei-Fu Shaw

Molecules 2021, 26(5), 1293; https://doi.org/10.3390/molecules26051293 - 27 Feb 2021

Cited by 12 | Viewed by 3418

Abstract

Generally, bacteriochlorophyllides were responsible for the photosynthesis in bacteria. Seven types of bacteriochlorophyllides have been disclosed. Bacteriochlorophyllides a/b/g could be synthesized from divinyl chlorophyllide a. The other bacteriochlorophyllides c/d/e/f could be synthesized [...] Read more.

Generally, bacteriochlorophyllides were responsible for the photosynthesis in bacteria. Seven types of bacteriochlorophyllides have been disclosed. Bacteriochlorophyllides a/b/g could be synthesized from divinyl chlorophyllide a. The other bacteriochlorophyllides c/d/e/f could be synthesized from chlorophyllide a. The chemical structure and synthetic route of bacteriochlorophyllides were summarized in this review. Furthermore, the potential applications of bacteriochlorophyllides in photosensitizers, immunosensors, influence on bacteriochlorophyll aggregation, dye-sensitized solar cell, heme synthesis and for light energy harvesting simulation were discussed. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Full article ">Figure 1
The compounds relative to bacteriochlorophyllides. Full article ">Figure 2
The relation between bacteriochlorophyllide a and bacteriochlorophyll a. Full article ">Figure 3
Biosynthetic routes among various bacteriochlorophyllides. The structure differences of bacteriochlorophyllide derivatives to bacteriochlorophyllide a were highlighted with spots. Full article ">Figure 4
Some applications of bacteriochlorophyllides derivatives. Full article ">Figure 5
Schematic drawing of bacteriochlorophyllides used as immunosensors (Modified from Mahato et al. [<a href="#B56-molecules-26-01293" class="html-bibr">56</a>,<a href="#B58-molecules-26-01293" class="html-bibr">58</a>]). Full article ">Figure 6
Schematic drawing of bacteriochlorophyllides used as a component of dye-sensitized solar cells (Modified from Shalini et al. [<a href="#B70-molecules-26-01293" class="html-bibr">70</a>]). Full article ">

17 pages, 5558 KiB

Open AccessReview

Potential Treatment of Breast and Lung Cancer Using Dicoma anomala, an African Medicinal Plant

by Alexander Chota, Blassan P. George and Heidi Abrahamse

Molecules 2020, 25(19), 4435; https://doi.org/10.3390/molecules25194435 - 27 Sep 2020

Cited by 18 | Viewed by 5484

Abstract

Globally, cancer has been identified as one of the leading causes of death in public health. Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are known to be less toxic to the normal cells and are classified into acetylenic [...] Read more.

Globally, cancer has been identified as one of the leading causes of death in public health. Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are known to be less toxic to the normal cells and are classified into acetylenic compounds, phenolics, terpenes, and phytosterols. Dicoma anomala is a perennial herb belonging to the family Asteraceae and is widely distributed in Sub-Saharan Africa and used in the treatment of cancer, malaria, fever, diabetes, ulcers, cold, and cough. This review aimed at highlighting the benefits of D. anomala in various therapeutic applications with special reference to the treatment of cancers and the mechanisms through which the plant-derived agents induce cell death. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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30 pages, 3008 KiB

Open AccessReview

Flavonoids and Related Members of the Aromatic Polyketide Group in Human Health and Disease: Do They Really Work?

by Jan Tauchen, Lukáš Huml, Silvie Rimpelova and Michal Jurášek

Molecules 2020, 25(17), 3846; https://doi.org/10.3390/molecules25173846 - 24 Aug 2020

Cited by 19 | Viewed by 5219

Abstract

Some aromatic polyketides such as dietary flavonoids have gained reputation as miraculous molecules with preeminent beneficial effects on human health, for example, as antioxidants. However, there is little conclusive evidence that dietary flavonoids provide significant leads for developing more effective drugs, as the [...] Read more.

Some aromatic polyketides such as dietary flavonoids have gained reputation as miraculous molecules with preeminent beneficial effects on human health, for example, as antioxidants. However, there is little conclusive evidence that dietary flavonoids provide significant leads for developing more effective drugs, as the majority appears to be of negligible medicinal importance. Some aromatic polyketides of limited distribution have shown more interesting medicinal properties and additional research should be focused on them. Combretastatins, analogues of phenoxodiol, hepatoactive kavalactones, and silymarin are showing a considerable promise in the advanced phases of clinical trials for the treatment of various pathologies. If their limitations such as adverse side effects, poor water solubility, and oral inactivity are successfully eliminated, they might be prime candidates for the development of more effective and in some case safer drugs. This review highlights some of the newer compounds, where they are in the new drug pipeline and how researchers are searching for additional likely candidates. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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17 pages, 4579 KiB

Open AccessFeature PaperReview

Contiguous Quaternary Carbons: A Selection of Total Syntheses

by Alina Eggert, Christoph Etling, Dennis Lübken, Marius Saxarra and Markus Kalesse

Molecules 2020, 25(17), 3841; https://doi.org/10.3390/molecules25173841 - 24 Aug 2020

Cited by 9 | Viewed by 4898

Abstract

Contiguous quaternary carbons in terpene natural products remain a major challenge in total synthesis. Synthetic strategies to overcome this challenge will be a pivotal prerequisite to the medicinal application of natural products and their analogs or derivatives. In this review, we cover syntheses [...] Read more.

Contiguous quaternary carbons in terpene natural products remain a major challenge in total synthesis. Synthetic strategies to overcome this challenge will be a pivotal prerequisite to the medicinal application of natural products and their analogs or derivatives. In this review, we cover syntheses of natural products that exhibit a dense assembly of quaternary carbons and whose syntheses were uncompleted until recently. While discussing their syntheses, we not only cover the most recent total syntheses but also provide an update on the status quo of modern syntheses of complex natural products. Herein, we review (±)-canataxpropellane, (+)-waihoensene, (–)-illisimonin A and (±)-11-O-debenzoyltashironin as prominent examples of natural products bearing contiguous quaternary carbons. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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