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Search Results (1,261)

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17 pages, 681 KiB  
Review
Nutritional Factors Related to Canine Gallbladder Diseases—A Scoping Review
by Fabio Alves Teixeira, Kathleen Moira Aicher and Ricardo Duarte
Vet. Sci. 2025, 12(1), 5; https://doi.org/10.3390/vetsci12010005 (registering DOI) - 28 Dec 2024
Viewed by 503
Abstract
Gallbladder mucocele, cholelithiasis, choledocholithiasis, and cholecystitis are significant contributors to morbidity and mortality in dogs. The exact etiology of these conditions remains poorly understood, though various factors, such as endocrinopathies, dyslipidemia, and impaired gallbladder motility, have been suggested as potential contributors. Surgical intervention [...] Read more.
Gallbladder mucocele, cholelithiasis, choledocholithiasis, and cholecystitis are significant contributors to morbidity and mortality in dogs. The exact etiology of these conditions remains poorly understood, though various factors, such as endocrinopathies, dyslipidemia, and impaired gallbladder motility, have been suggested as potential contributors. Surgical intervention has been described as the first choice of treatment when biliary rupture or obstruction is suspected; however, medical management may be an important part of therapeutic or preventative strategy. Reports of medical management typically involve the use of a choleretic used to stimulate the flow of bile into the duodenum or substances that act as a “hepatoprotective” agent such as S-adenosylmethionine. In people, some nutrients appear to modify bile flow and are used as agents in the prevention and treatment of these conditions in the gallbladder. This paper provides a review of the literature about possible nutritional factors involved in the pathogenesis and treatment of canine gallbladder mucocele and cholelithiasis. Opportunities for the prevention and treatment of common biliary diseases in dogs may include the reduction of dietary fat, control of hyperlipidemia with omega-3 and fiber supplementation, ensuring an adequate supply of amino acids such as methionine and tryptophan, and the evaluation of vitamins such as vitamin D. Full article
(This article belongs to the Special Issue Effects of Diet on Small Animal Health—2nd Edition)
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<p>Canine gallbladder conditions. (<b>A</b>) Ultrasound image of biliary sludge. (<b>B</b>) Ultrasound image of a gallbladder almost entirely filled by cholelithiasis. (<b>C</b>) Ultrasound image of gallbladder mucocele. (<b>D</b>) Photograph of a gallbladder after cholecystectomy indicated due to the risk of gallbladder rupture (<b>E</b>) and the same gallbladder after wall incision.</p>
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19 pages, 2335 KiB  
Article
Alpinetin Exhibits Antioxidant and Anti-Inflammatory Effects in C57BL/6 Mice with Alcoholic Liver Disease Induced by the Lieber–DeCarli Ethanol Liquid Diet
by Tatjana Radosavljevic, Milica Brankovic, Jasmina Djuretić, Jelica Grujic-Milanovic, Marijana Kovacic, Jovan Jevtic, Sanja Stankovic, Janko Samardzic, Danijela Vucevic and Vladimir Jakovljevic
Int. J. Mol. Sci. 2025, 26(1), 86; https://doi.org/10.3390/ijms26010086 - 26 Dec 2024
Viewed by 169
Abstract
Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, [...] Read more.
Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited. Alpinetin, a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential hepatoprotective effects, though its efficacy in ALD remains unexplored. This study investigated the hepatoprotective effects of alpinetin using a Lieber–DeCarli ethanol liquid diet model of ALD in C57BL/6 mice. Mice were divided into three groups: the control group, the ethanol group, and the ethanol group treated with alpinetin. Serum activity of ALT, AST, γ-GT, and ALP was measured to assess liver function, along with antioxidative and oxidative/nitrosative stress markers in liver tissue. Pro-inflammatory cytokines and endoplasmic reticulum (ER) stress parameters in liver tissue were also evaluated. Histological assessment of disease activity was performed using the SALVE grading and staging system. Treatment with alpinetin significantly reduced serum levels of ALT, AST, γ-GT, and oxidative/nitrosative stress markers while increasing antioxidative markers. The levels of pro-inflammatory cytokines and ER stress parameters were significantly decreased. Histological analysis demonstrated reduced steatosis, hepatocyte ballooning, and inflammation. These findings suggest that alpinetin holds promise as a potential therapeutic agent for managing ALD. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Atherosclerosis)
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<p>The effects of alpinetin on oxidative/nitrosative stress parameters: (<b>a</b>) MDA, (<b>b</b>) AOPP, (<b>c</b>) O<sub>2</sub><sup>−</sup>, (<b>d</b>) NO<sub>2</sub><sup>−</sup>, (<b>e</b>) PAB. The values are represented by mean ± SD; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05. Abbreviations: MDA—malondialdehyde; AOPP—advanced oxidation protein product; (<b>c</b>) O<sub>2</sub><sup>−</sup> superoxide anion radical; (<b>d</b>) NO<sub>2</sub>—nitrite; (<b>e</b>) PAB—pro-oxidant–antioxidant balance; C—control group; E—ethanol group; E+Alp—ethanol + alpinetin group.</p>
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<p>The effects of alpinetin on antioxidative parameters: (<b>a</b>) CAT, (<b>b</b>) SOD, (<b>c</b>) total glutathione, (<b>d</b>) GSH, (<b>e</b>) GSSG, (<b>f</b>) GPx, (<b>g</b>) GSH/GSSG ratio. The values are represented by mean ± SD; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05, respectively. Abbreviations: CAT—catalase; SOD—superoxide dismutase; GSH—reduced glutathione; GSSG—oxidized glutathione; GPx—glutathione peroxidase; C—control group; E—ethanol group; E+Alp—ethanol + alpinetin group.</p>
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<p>The effects of alpinetin on (<b>a</b>) IFN-γ, (<b>b</b>) IL-4, and (<b>c</b>) MPO activity. The values are represented by mean ± SD; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01. Abbreviations: IFN-γ—interferon-gamma; IL-4—interleukin 4; MPO—myeloperoxidase; C—control group; E—ethanol group; E+Alp—ethanol + alpinetin group.</p>
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<p>The effects of alpinetin on the expression of the ER stress proteins (<b>a</b>) GADD153, (<b>b</b>) GRP 78, (<b>c</b>) ATF-4, (<b>d</b>) Western blot analyses of GADD153, GRP 78, ATF-4, and β-actin in liver tissue (n = 6) (<a href="#app1-ijms-26-00086" class="html-app">Figure S2</a>). Abbreviations: GADD—growth arrest and DNA damage-inducible gene 153; GRP 78—glucose-regulated protein 78; ATF 4—activating transcription factor 4; C—control group; E—ethanol group; E+Alp—ethanol + alpinetin group. The values are represented by mean ± SD; *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>(<b>A</b>) Normal liver histology (<b>A</b>(a)); liver histology of mice in the E group (<b>A</b>(b,c,e,g)); liver histology of mice in the E+Alp group (<b>A</b>(d,f,h)). (<b>A</b>(b)) hepatocellular injury (ballooning). Numerous hepatocytes are ballooned, showing cytoplasmic clearing (arrows). The image also shows a central vein (asterisk). H&amp;E stain, magnification ×200; (A(c)) Numerous hepatocytes are ballooned, showing cytoplasmic clearing, with some exhibiting Mallory bodies (arrows). H&amp;E stain, magnification ×400; (<b>A</b>(g)) Steatosis. Numerous hepatocytes exhibit fatty changes, with fat vacuoles observed in the cytoplasm (arrows). The image also shows a central vein (asterisk). H&amp;E stain, magnification ×400; (<b>A</b>(e)) lobular neutrophils. Numerous neutrophils are present between hepatocytes (arrow). H&amp;E stain, magnification ×400. (<b>A</b>(d)) The depicted hepatocytes do not show ballooning. H&amp;E stain, magnification ×200; (<b>A</b>(h)) A few hepatocytes exhibit fatty changes with sparse microdroplets (arrows). H&amp;E stain, magnification ×400; (<b>A</b>(f)) Scattered neutrophils are present between hepatocytes. H&amp;E stain, magnification ×400. (<b>B</b>) Histology score of hepatocellular injury, lobular neutrophils (activity grade), and steatosis in the E and E+Alp groups (*** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05 vs. E group).</p>
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13 pages, 2838 KiB  
Article
Anti-Tumor Effects of Vespa bicolor Venom on Liver Cancer: In Vitro and In Vivo Studies
by Yong-Hua Wu, Feng Xiong, Zheng-Wen Ou, Jing-An Wang, Jing Cui, Lin Jiang and Wen-Jian Lan
Toxins 2025, 17(1), 4; https://doi.org/10.3390/toxins17010004 - 25 Dec 2024
Viewed by 368
Abstract
Despite the popular belief in the anti-tumor properties of Vespa bicolor venom (VBV), there is limited scientific evidence to support this claim. This study is the first to examine the anti-tumor effects of VBV on liver cancer, both alone and in combination with [...] Read more.
Despite the popular belief in the anti-tumor properties of Vespa bicolor venom (VBV), there is limited scientific evidence to support this claim. This study is the first to examine the anti-tumor effects of VBV on liver cancer, both alone and in combination with cisplatin (DDP), through in vitro and in vivo experiments. In vitro experiments evaluated VBV and its combination with DDP on HepG2 cell proliferation, invasion, migration, and apoptosis. Animal studies examined the tumor-suppressive effects, safety (hepatotoxicity and nephrotoxicity), and immune impact of these treatments in tumor-bearing mice. VBV monotherapy significantly inhibited the growth of HepG2 cells by suppressing their proliferation and invasion and induced apoptosis in vitro. Notably, low VBV concentrations significantly promoted the proliferation of normal liver cells (L-02), suggesting a hepatoprotective effect. In vivo, VBV monotherapy enhanced immune function and exhibited tumor suppression comparable to DDP monotherapy but did not induce significant liver or kidney damage. In addition, VBV combined with DDP synergistically enhanced the anti-tumor effects of DDP, compensating for its limited apoptosis-inducing activity and insufficient enhancement of immune function. Initial studies have shown the strong potential of VBV as an anti-liver-tumor drug, highlighting its unique clinical value. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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<p>Quality evaluation of collected <span class="html-italic">Vespa bicolor</span> venom (VBV) samples, including (<b>a</b>) analysis of protein components by SDS-PAGE electrophoresis and (<b>b</b>) HPLC fingerprint analysis.</p>
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<p>In vitro efficacy of VBV as a treatment for liver cancers either as a monotherapy or in conjunction with the chemotherapeutic drug cisplatin (DDP). (<b>a</b>) Cytotoxic effects of varying concentrations of VBV on HepG2 cells and L-02 cells. (<b>b</b>) Comparative analysis of the cytotoxicity of DDP alone versus its combination with 15 µg/mL VBV on HepG2 cells. (<b>c</b>) Comparative analysis of the cytotoxicity of DDP alone and in combination with 15 µg/mL VBV on L-02 cells. Data are expressed as means ± SD. Each experiment represents the mean values of six independent experiments. * <span class="html-italic">p</span> &lt; 0.05 compared with negative controls.</p>
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<p>In vitro anti-tumor efficacy of VBV as a monotherapy against HepG2 cells. The effects of varying concentrations of VBV on HepG2 cells: (<b>a</b>) proliferation assessed using EdU, (<b>b</b>) migration assessed using scratch assays, (<b>c</b>) invasion measured using Transwell assays, and (<b>d</b>) apoptosis analyzed via flow cytometry. Data are expressed as means ± SD. Each experiment represents the mean values of three independent experiments. *** <span class="html-italic">p</span> &lt; 0.001, significant difference; ns, no significant difference.</p>
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<p>In vitro anti-tumor efficacy of combined with DDP. The effects of 15 µg/mL VBV combined with 4 µg/mL DDP on HepG2 cells: (<b>a</b>) proliferation assessed using EdU assays; (<b>b</b>) migration assessed using scratch assay; (<b>c</b>) invasion measured using Transwell assays; and (<b>d</b>) apoptosis analyzed via flow cytometry. Data are expressed as means ± SD. Each experiment represents the mean values of three independent experiments. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, significant difference; ns, no significant difference.</p>
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<p>Tumor-suppressive effects of VBV alone and in combination with DDP in the murine model. (<b>a</b>) Weight changes of mice across different treatment groups over 20 days after tumor implantation. (<b>b</b>) Changes in tumor volume among the treatment groups. (<b>c</b>) Tumor weights in each group following 20 days of drug treatment. (<b>d</b>) Images of tumor tissue in each experimental group. (<b>e</b>) HE stained images of tumors in each experimental group. Data represent mean ± SD; n = 6 mice/group. * <span class="html-italic">p</span> &lt; 0.05, significant difference.</p>
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<p>Hepatorenal toxicity and immunomodulatory effects of VBV alone and in combination with DDP evaluated in a murine model. Following 20 days of various drug treatments, we analyzed the differences in the following: (<b>a</b>) liver index, (<b>b</b>) kidney index, (<b>d</b>) spleen index, and (<b>e</b>) thymus index (<b>f</b>), as well as (<b>c</b>) ALT and (<b>d</b>) AST levels in serum among the different groups of mice. Data represent mean ± SD; n = 6 mice/group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, significant difference; ns, no significant difference.</p>
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15 pages, 14302 KiB  
Article
Hepatoprotective Activity and Oxidative Stress Reduction of an Arctium tomentosum Mill. Root Extract in Mice with Experimentally Induced Hepatotoxicity
by Arailym Aitynova, Bogdan Sevastre, Irina Ielciu, Daniela Hanganu, Neli-Kinga Olah, Nailya Ibragimova, Tamara Shalakhmetova, Daniela Benedec, Marina Lyu, Arkadiy Krasnoshtanov and Tamari Gapurkhaeva
Livers 2024, 4(4), 696-710; https://doi.org/10.3390/livers4040048 - 17 Dec 2024
Viewed by 604
Abstract
Background: The use of natural hepatoprotective remedies represents an important path in modern phytotherapy. Objectives: In this context, our research aims to evaluate the phytochemical composition and the hepatoprotective and oxidative stress reduction potential of an Arctium tomentosum Mill. root extract. Methods: The [...] Read more.
Background: The use of natural hepatoprotective remedies represents an important path in modern phytotherapy. Objectives: In this context, our research aims to evaluate the phytochemical composition and the hepatoprotective and oxidative stress reduction potential of an Arctium tomentosum Mill. root extract. Methods: The phenolic profile of the tested extract, prepared by the subcritical fluid-assisted method were qualitatively and quantitatively analyzed by spectrophotometrical and HPLC/DAD/ESI methods. In vitro antioxidant capacity was assessed using DPPH and FRAP assays. Hepatoprotective activity of the extract was assessed on a model of CCl4 experimentally induced hepatotoxicity in mice. Results: Phytochemical assays revealed the presence of important polyphenols, such as chlorogenic acid (17.20 ± 0.65 μg/mL) and acacetin 7-O-glucoside (56.80 ± 1.66 μg/mL). In vitro, the tested extract exhibited a significant oxidative stress reduction capacity, while in vivo it showed a dose-dependent hepatoprotective effect indicated by an improvement in plasma proteins profile and down-regulation of plasma transaminase activity (ALAT, ASAT, GGT). In liver tissue, the extract partially restored the activity of GPx, CAT, and SOD and attenuated lipid peroxidation. The protective effect of the A. tomentosum root extract was supported by the alleviation of histological injuries of the liver (centrilobular necrosis, granulocytic infiltrate, and fibrosis). Conclusions: The A. tomentosum subcritical fluid-assisted root extract proved to be able to provide a significant hepatoprotective effect mainly through an antioxidant mechanism. Full article
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<p>Effect of <span class="html-italic">A. tomentosum</span> extract on alanine aminotransferase (ALAT) (<b>A</b>); aspartate amino transferase (ASAT) (<b>B</b>); gamma glutamyl transferase (GGT) activity (<b>C</b>); total protein (<b>D</b>) and albumins concentration (<b>E</b>) (mean ± SD, 5 animals/group). ## <span class="html-italic">p</span> &lt; 0.01, compared to the control group; * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 compared to the group treated by CCl<sub>4</sub> only (two-way ANOVA followed by Bonferroni post-test).</p>
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<p>Effect of <span class="html-italic">A. tomentosum</span> extract on glutathione peroxidase (GPx) (<b>A</b>); catalase (CAT) (<b>B</b>); superoxide dismutase (SOD) (<b>C</b>); and malondialdehyde (MDA) (<b>D</b>) (mean ± SD, 5 animals/group). ### <span class="html-italic">p</span> &lt; 0.01, compared to the control group; * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 compared to the group treated by CCl<sub>4</sub> only (two-way ANOVA followed by Bonferroni post-test).</p>
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<p>Effects of <span class="html-italic">A. tomentosum</span> subcritical fluid-assisted root extract on the histologic aspect of the liver: (<b>A</b>,<b>F</b>) the negative control group; (<b>B</b>,<b>G</b>) the positive control group receiving only carbon tetrachloride (1 mL/b.w.) showed inflammatory infiltrate (black arrow) and hepatocyte necrosis (doted black arrow); groups receiving therapy with the extract in a dose of (<b>C</b>,<b>H</b>) 50 mg/b.w.; (<b>D</b>,<b>I</b>) 200 mg/b.w.; and (<b>E</b>,<b>J</b>) 400 mg/b.w. Duration: (<b>A</b>–<b>E</b>) four weeks; (<b>F</b>–<b>J</b>) six weeks. Hematoxylin and Eosin stain; Bar, 100 μm.</p>
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<p>Effects of <span class="html-italic">A. tomentosum</span> subcritical fluid-assisted root extract on the histologic aspect of the liver: (<b>A</b>,<b>F</b>) the negative control group; (<b>B</b>,<b>G</b>) the positive control group receiving only carbon tetrachloride (1 mL/b.w.) showed inflammatory infiltrate (black arrow) and hepatocyte necrosis (doted black arrow); groups receiving therapy with the extract in a dose of (<b>C</b>,<b>H</b>) 50 mg/b.w.; (<b>D</b>,<b>I</b>) 200 mg/b.w.; and (<b>E</b>,<b>J</b>) 400 mg/b.w. Duration: (<b>A</b>–<b>E</b>) four weeks; (<b>F</b>–<b>J</b>) six weeks. Hematoxylin and Eosin stain; Bar, 100 μm.</p>
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<p>Protective effects of <span class="html-italic">A. tomentosum</span> subcritical fluid-assisted root against experimentally induced hepatotoxicity (green arrows represent the effect of <span class="html-italic">A. tomentosum</span> subcritical fluid-assisted root extract; red arrows represent the mechanism of CCl<sub>4</sub> hepatotoxicity).</p>
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16 pages, 2357 KiB  
Article
The Effect of Quercetin on Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Beclin1, P62, and LC3: An Experimental Study
by Ioannis Katsaros, Maria Sotiropoulou, Michail Vailas, Fotini Papachristou, Paraskevi Papakyriakopoulou, Marirena Grigoriou, Nikolaos Kostomitsopoulos, Alexandra Giatromanolaki, Georgia Valsami, Alexandra Tsaroucha and Dimitrios Schizas
Nutrients 2024, 16(24), 4282; https://doi.org/10.3390/nu16244282 - 11 Dec 2024
Viewed by 685
Abstract
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins [...] Read more.
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Methods: Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Results: Quercetin-treated groups showed significant reductions in NAS compared to controls (p = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Conclusions: Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application. Full article
(This article belongs to the Special Issue Fruits and Vegetable Bioactive Substances and Nutritional Value)
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<p>Steatohepatitis prevalence was stratified by each experimental group ((<b>A</b>) Baseline, (<b>B</b>) Control, (<b>C</b>) QUE 1, (<b>D</b>) QUE 2). Orange segments indicate the prevalence of steatohepatitis, while blue segments represent the prevalence of fatty liver. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin.</p>
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<p>Representative immunoblotting images and densitometric analysis of p62 expression. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> &lt; 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
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<p>Representative immunoblotting images and densitometric analysis of p62 expression. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> &lt; 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
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<p>Representative immunoblotting images and densitometric analysis of LC3A-I expression. In general, LC3A-II was undetectable. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> &lt; 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
Full article ">Figure 3 Cont.
<p>Representative immunoblotting images and densitometric analysis of LC3A-I expression. In general, LC3A-II was undetectable. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> &lt; 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
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<p>Representative immunoblotting images and densitometric analysis of LC3B-I and -II expression. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> ≤ 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
Full article ">Figure 4 Cont.
<p>Representative immunoblotting images and densitometric analysis of LC3B-I and -II expression. The P fraction contains autophagy-related vesicles, and the SP fraction contains cytoplasmic soluble proteins. The bold horizontal lines in the graphs represent the geometric means. Where #, <span class="html-italic">p</span> ≤ 0.05 vs. the corresponding P fraction. QUE 1—low-dose quercetin, QUE 2—high-dose quercetin, CON—control, BSL—baseline.</p>
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17 pages, 3918 KiB  
Article
Long-Term Aerobic Exercise Enhances Hepatoprotection in MAFLD by Modulating Exosomal miR-324 via ROCK1
by Yang Zhang, Qiangman Wei, Xue Geng and Guoliang Fang
Metabolites 2024, 14(12), 692; https://doi.org/10.3390/metabo14120692 - 9 Dec 2024
Viewed by 596
Abstract
Background: Insulin resistance (IR) is central to the progression of non-alcoholic fatty liver disease (MAFLD). While aerobic exercise reduces hepatic fat and enhances insulin sensitivity, the specific mechanisms—particularly those involving exosomal pathways—are not fully elucidated. Method: Exosomes were isolated from 15 MAFLD patients’ [...] Read more.
Background: Insulin resistance (IR) is central to the progression of non-alcoholic fatty liver disease (MAFLD). While aerobic exercise reduces hepatic fat and enhances insulin sensitivity, the specific mechanisms—particularly those involving exosomal pathways—are not fully elucidated. Method: Exosomes were isolated from 15 MAFLD patients’ plasma following the final session of a 12-week aerobic exercise intervention. Liver fat content was measured using MRI-PDFF, and metabolic parameters were assessed via OGTT, HOMA-IR, QUICKI, and VO2 max. Co-culture experiments evaluated the effects of exercise-derived exosomes on IR signaling pathways. miRNA microarray analysis identified miR-324, which was quantified in high-fat diet (HFD) mice with and without exercise and compared between athletes and sedentary controls. Functional assays assessed miR-324’s role in glucose and lipid metabolism, while luciferase reporter and Western blot assays confirmed ROCK1 as its direct target. Result: Aerobic exercise significantly reduced liver fat and improved insulin sensitivity in both MAFLD patients and HFD mice. Notably, exosomal miR-324 levels were lower in athletes than sedentary controls, indicating an inverse association with insulin sensitivity. Post-exercise, precursor and mature miR-324 increased in adipose tissue and decreased in muscle, suggesting its adipose origin and inverse regulation. Functional assays demonstrated that miR-324 modulates insulin resistance by targeting ROCK1. Conclusion: Exercise-induced exosomal miR-324 from adipose tissue targets ROCK1, revealing a novel mechanism by which aerobic exercise confers hepatoprotection against insulin resistance in MAFLD. These findings enhance our understanding of how exercise influences metabolic health and may inform future therapeutic strategies for managing MAFLD and related conditions. Full article
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<p>MRI-PDFF effects and OGTT results of 12-week aerobic exercise on MAFLD patients. (<b>A</b>) MRI-PDFF imaging showing reduction in liver fat content after 12 weeks of aerobic exercise in MAFLD patients. (<b>B</b>) OGTT results indicating improved glucose tolerance in MAFLD patients post-training.</p>
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<p>(<b>a</b>) pet imaging with [<sup>18</sup>F]-ftha showing reduced fat accumulation in the HFD + exe group. (<b>b</b>) liver histology (H&amp;E, oil red o, and Masson’s staining) showing decreased lipid deposition and fibrosis in the HFD + exe group. (<b>c</b>–<b>e</b>) weights of liver (<b>c</b>), inguinal fat (iwat) (<b>d</b>), and epididymal fat (ewat) (<b>e</b>) reduced in the HFD + exe group. (<b>f</b>–<b>h</b>) improved liver triglycerides (tg) (<b>f</b>), ast (<b>g</b>), and alt (<b>h</b>) in the HFD + exe group. (<b>i</b>) increased liver insulin signaling (pAKT and pgsk3) in the HFD + exe group.</p>
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<p>Characterization and functional validation of plasma-derived exosomes in exercise-conditioned individuals. (<b>A</b>–<b>D</b>) Exosomal morphology, surface markers, and concentration, confirming the purity and consistency of exosome isolation. (<b>E</b>–<b>H</b>) Uptake of exosomes by HepG2 cells and improvements in glucose uptake, glycogen, and triglyceride levels, indicating potential insulin resistance mitigation. (<b>I</b>) Western blot showing enhanced insulin signaling in cells treated with exercise-derived exosomes.</p>
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<p>MiR-324-5p as a key exosomal miRNA regulating glucose and lipid metabolism. (<b>A</b>,<b>B</b>) Heatmap and relative expression of miRNAs, identifying miR-324-5p as significantly upregulated in exercise-derived exosomes. (<b>C</b>,<b>D</b>) Elevated miR-324-5p in high-glucose/high-fat-treated cells and MAFLD patients. (<b>E</b>–<b>J</b>) Functional effects of miR-324-5p overexpression and inhibition on glycogen and triglyceride content in HepG2 cells, demonstrating its role in metabolism regulation. <span class="html-italic">p</span> &lt; 0.01 (**), <span class="html-italic">p</span> &lt; 0.001 (***), and <span class="html-italic">p</span> &lt; 0.0001 (****). All statistical analyses were conducted using GraphPad Prism version 5.0, with <span class="html-italic">p</span> &lt; 0.05 considered statistically significant.</p>
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<p>MiR-324-5p targets ROCK1 to modulate insulin signaling pathways. (<b>a</b>–<b>c</b>) miR-324-5p binding to ROCK1 3′UTR confirmed by luciferase assay, identifying ROCK1 as a direct target. (<b>d</b>,<b>e</b>) Upregulation of ACC and PEPCK with miR-324-5p overexpression. (<b>f</b>–<b>h</b>) Western blot analysis showing ROCK1 downregulation, enhanced insulin signaling, and similar effects in ROCK1 siRNA-treated cells. <span class="html-italic">p</span> &lt; 0.05 (*). All statistical analyses were conducted using GraphPad Prism version 5.0, with <span class="html-italic">p</span> &lt; 0.05 considered statistically significant.</p>
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<p>Adipose tissue as the primary source of exercise-induced exosomal miR-324-5p. (<b>a</b>,<b>b</b>) Relative levels of pre- and mature miR-324 in liver, muscle, and adipose tissue, with significant post-exercise increases in adipose tissue, suggesting it as the primary source.</p>
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<p>Elevated exosomal miR-324-5p levels in elite athletes compared to sedentary controls. Plasma levels of exosomal miR-324-5p in athletes vs. sedentary controls, showing significantly higher levels in athletes, indicating that sustained physical training may upregulate miR-324-5p expression.</p>
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18 pages, 782 KiB  
Review
The Extraction, Biosynthesis, Health-Promoting and Therapeutic Properties of Natural Flavanone Eriodictyol
by Haiaolong Yin, Yaxian Li, Yi Feng, Lei Tian and Ye Li
Nutrients 2024, 16(23), 4237; https://doi.org/10.3390/nu16234237 - 8 Dec 2024
Viewed by 921
Abstract
Eriodictyol is a flavanone compound commonly found in several edible plants. Ultrasound-assisted extraction and high-performance liquid chromatography (HPLC) are commonly used methods for the separation and analysis of eriodictyol. Many studies show that some micro-organisms can produce eriodictyol as a host. What is [...] Read more.
Eriodictyol is a flavanone compound commonly found in several edible plants. Ultrasound-assisted extraction and high-performance liquid chromatography (HPLC) are commonly used methods for the separation and analysis of eriodictyol. Many studies show that some micro-organisms can produce eriodictyol as a host. What is more, eriodictyol has a wide range of health benefits, including skincare, neuroprotective, hypoglycemic, anti-inflammatory, and antioxidant activities. In addition, the therapeutic properties of eriodictyol are cardioprotective, hepatoprotective, anticancer, with protective effects on the lungs and kidneys, and so on. This review examines the extraction, biosynthesis, and health and therapeutic properties of the natural compound eriodictyol and its value in medicine and food. Full article
(This article belongs to the Special Issue Polyphenol-Rich Foods on Human Health and Diseases)
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<p>The structure of eriodictyol.</p>
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<p>The potential applications and further use of eriodictyol.</p>
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11 pages, 544 KiB  
Article
Protective Effects of a Brassica nigra Sprout Hydroalcoholic Extract on Lipid Homeostasis, Hepatotoxicity, and Nephrotoxicity in Cyclophosphamide-Induced Toxicity in Rats
by Hassan Barakat, Thamer Aljutaily, Raghad I. Alkhurayji, Huda Aljumayi, Khalid S. Alhejji and Sami O. Almutairi
Metabolites 2024, 14(12), 690; https://doi.org/10.3390/metabo14120690 - 8 Dec 2024
Viewed by 650
Abstract
Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid [...] Read more.
Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg−1 intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 250 mg kg−1 by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 500 mg kg−1 by oral gavage daily for three weeks. Results: The results indicated a significant increase (p < 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg−1 significantly (p < 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg−1, performing even better than 250 mg kg−1. Administrating BNSE at 250 or 500 mg kg−1 improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg−1 of BNSE with 500 mg kg−1 showed that administrating 250 mg kg−1 attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg−1 was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg−1 and 34.93% for BNSE at 500 mg kg−1. Higher efficiency was noticed for BNSE at 250 and 500 mg kg−1 regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg−1 was shown. The best treatment was BNSE at 500 mg kg−1, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended. Full article
(This article belongs to the Special Issue Plants and Plant-Based Foods for Metabolic Disease Prevention)
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<p>Effects of <span class="html-italic">B. nigra</span> sprout extract at different doses on AI in rats with CYP-induced immunosuppression (mean ± SE), <span class="html-italic">n</span> = 8. <sup>a,b,</sup> and <sup>c</sup>: bars not sharing similar letters differed significantly (<span class="html-italic">p</span> &gt; 0.05), for experimental groups, see Materials and Methods.</p>
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27 pages, 2262 KiB  
Review
Betalains: A Narrative Review on Pharmacological Mechanisms Supporting the Nutraceutical Potential Towards Health Benefits
by Renata M. Martinez, Cristina P. B. Melo, Ingrid C. Pinto, Soraia Mendes-Pierotti, Josiane A. Vignoli, Waldiceu A. Verri and Rubia Casagrande
Foods 2024, 13(23), 3909; https://doi.org/10.3390/foods13233909 - 3 Dec 2024
Viewed by 1056
Abstract
Betalains are naturally occurring pigments sourced mainly from Beta vulgaris (beetroot), Hylocereus spp. (dragon fruit), Amaranthus spp., and Opuntia spp. Betalains are widely used for their vibrant colors and health-promoting properties. These nitrogenous, water-soluble pigments are crucial colorants in the food industry, responsible [...] Read more.
Betalains are naturally occurring pigments sourced mainly from Beta vulgaris (beetroot), Hylocereus spp. (dragon fruit), Amaranthus spp., and Opuntia spp. Betalains are widely used for their vibrant colors and health-promoting properties. These nitrogenous, water-soluble pigments are crucial colorants in the food industry, responsible for the red, purple, and yellow plant tissues, predominantly in the order Caryophyllales. They are grouped into betacyanins, with reddish-violet hues, and betaxanthins, yellow to orange. Examples include beetroot stems for betacyanins and yellow pitaya pulp for betaxanthins. Several pharmacological activities were reviewed in the scientific literature, describing their potential implications for human health. In this review, we focused on the main and latest studies on the pharmacological effects and mechanisms of betalains, including antioxidant, anti-inflammatory, antihypertensive, hypolipidemic, antidiabetic, hepatoprotective, neuroprotective, anticancer, and antimicrobial properties, in both in vitro and in vivo studies. Overall, betalain consumption is considered safe, with no major adverse effects or allergic reactions reported. We also approached topics such as the pharmacokinetics, bioavailability, stability, and enhanced stabilization of betalains. This article provides a comprehensive overview of bioactive potential of betalains, highlighting the biochemical mechanisms involved. The current knowledge broadens the clinical applicability of betalains, making them potential sources of nutraceutical compounds that can be used to develop functional foods. Full article
(This article belongs to the Special Issue Feature Review on Food Nutrition)
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<p>Chemical structures of the main subclasses of betalains. In the center, betalamic acid, the common precursor of betalains, gives rise to two main subclasses: betaxanthins (left, yellow/orange), which result from the conjugation of betalamic acid with amino acids or amines, and betacyanins (right, red/purple), formed by conjugation with cyclo-DOPA groups. Examples of betaxanthins include indicaxanthin, vulgaxanthin I, and tryptophan-betaxanthin, while examples of betacyanins include betanin, isobetanin, and neobetanin. The arrows indicate the biosynthetic pathways between betalamic acid and its derived subclasses. Adapted from Khan et al., 2015 [<a href="#B9-foods-13-03909" class="html-bibr">9</a>].</p>
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<p>A representative diagram highlights oxidative stress and inflammation as participants in the pathophysiological mechanisms of diseases and the inhibition of these processes by betalains. The excessive generation of free radicals triggers important molecular alterations including genetic mutation, lipid peroxidation, and the impairment of the endogenous antioxidant system. In addition, it can activate inflammatory signaling routes, resulting in inflammatory components that aggravate the damage. ROS: reactive oxygen species. RNS: reactive nitrogen species. Nrf2: nuclear factor erythroid 2-related factor 2. GSH: glutathione. SOD: superoxide dismutase. MDA: malondialdehyde. STAT3: signal transducer and activator of transcription 3. NF-κB: nuclear transcription factor kappa B. COX-2: cyclooxygenase-2. iNOS: inducible nitric oxide synthase. TNF-α: tumor necrosis factor-alpha. IL: interleukin. Created using <a href="http://BioRender.com" target="_blank">http://BioRender.com</a> (accessed on 21 November 2024).</p>
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<p>Representative scheme of the main biological properties and plant sources of betalains. Created using <a href="https://BioRender.com" target="_blank">https://BioRender.com</a> (accessed on 30 October 2024).</p>
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16 pages, 4204 KiB  
Article
Nebivolol Exerts Hepatoprotective Activity During CLP-Induced Sepsis by Modulating Oxidative Stress, Liver Regeneration, and AKT/MAPK Pathways in Rats
by Rahma Tharwat Sabra, Amany Abdlrehim Bekhit, Nourhan Tharwat Sabra, Nadia Ahmed Abd El-Moeze and Moustafa Fathy
Stresses 2024, 4(4), 800-815; https://doi.org/10.3390/stresses4040053 - 2 Dec 2024
Viewed by 445
Abstract
Sepsis is a potentially catastrophic organ dysfunction arising from an infection-induced immunologic reaction leading to severe inflammation, progression of septic shock, and damage to body organs. Sepsis is marked by noticeable hepatotoxicity caused by activating oxidative stress, inflammation, and apoptotic mechanisms. Through Cecal [...] Read more.
Sepsis is a potentially catastrophic organ dysfunction arising from an infection-induced immunologic reaction leading to severe inflammation, progression of septic shock, and damage to body organs. Sepsis is marked by noticeable hepatotoxicity caused by activating oxidative stress, inflammation, and apoptotic mechanisms. Through Cecal Ligation and Puncture (CLP) in rats, our study is the first to investigate the potential preventive effect of the antihypertensive medicine “Nebivolol” on sepsis-induced hepatotoxicity at a molecular level. Six groups of sixty albino Wistar rats (male) were randomly assigned. Biochemical and oxidative stress markers of liver function were measured. Additionally, apoptosis- and inflammatory-related gene and protein expressions were examined. Finally, the liver tissues were examined for histological assessments. The hepatic architecture was considerably altered by CLP, which also resulted in marked elevations of blood aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels, and hepatic malondialdehyde (MDA). In contrast, it decreased serum albumin level, hepatic superoxide dismutase (SOD) activity, and glutathione (GSH) level. It also significantly elevated all hepatic inflammatory mediators (Interlukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interlukin-1 beta (IL-1β)) and alleviated Interlukin-10 (IL-10). It magnified the expression of p-AKT/t-AKT, p-JNK1/2/t-JNK1/2, and p-p38/t-p38 proteins, raised Matrix Metalloproteinase 2/9 (MMP 2/9) and nuclear factor-kappa B (NF-κB) gene transcriptions, and lessened Vascular Endothelial Growth Factor (VEGF) gene expression. In contrast, Nebivolol administration dramatically mitigated all biochemical and histological changes obtained by CLP. The present finding demonstrated that Nebivolol succeeded, for the first time, in improving the hepatic injury obtained from CLP-evoked sepsis through modulating oxidative stress, inflammatory mediators, and apoptotic pathways through targeting the crosstalk between protein kinase B (AKT), NF-κB, and mitogen-activated protein kinase (MAPK), making Nebivolol a hopeful treatment for hepatic injury. Full article
(This article belongs to the Collection Feature Papers in Human and Animal Stresses)
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<p>Impact of Nebivolol on hepatic biochemical indicators in serum, (<b>a</b>) ALT, (<b>b</b>) AST, (<b>c</b>) ALP, (<b>d</b>) albumin, (<b>e</b>) direct bilirubin, and (<b>f</b>) total bilirubin after induction of CLP in rats. Data are exemplified as mean ± SEM. Following a one-way ANOVA test, the significant divisions among groups were analyzed using the Tukey–Kramar test, where ### <span class="html-italic">p</span>&lt; 0.001, contrasted with controlling sham control; ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP group.</p>
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<p>Influence of Nebivolol on oxidative status of liver tissue. (<b>a</b>) MDA content, (<b>b</b>) SOD activity, and (<b>c</b>) GSH level. Data are exemplified as mean ± SEM. Following a one-way ANOVA test, the significant divisions among groups were analyzed using the Tukey–Kramar test, where ### <span class="html-italic">p</span> &lt; 0.001, contrasted with sham control; *** <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP group; <span>$</span> <span class="html-italic">p</span> &lt; 0.05 and <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01, contrasted with CLP + Neb4 group.</p>
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<p>Impact of Nebivolol on (<b>a</b>) <span class="html-italic">TNF-α</span>, (<b>b</b>) IL<span class="html-italic">-β</span>, (<b>c</b>) <span class="html-italic">IL-</span>6, and (<b>d</b>) <span class="html-italic">IL-</span>10 cytokines in hepatic tissues. Data are exemplified as mean ± SEM. Following a one-way ANOVA test, the significant divisions among groups were analyzed using the Tukey–Kramar test, where ### <span class="html-italic">p</span>&lt; 0.001, contrasted with sham control; ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP group; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01, and <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP + Neb4 group.</p>
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<p>Effect of Nebivolol on (<b>a</b>) <span class="html-italic">MMP-2</span>, (<b>b</b>) <span class="html-italic">MMP-9</span>, (<b>c</b>) <span class="html-italic">VEGF</span>, and (<b>d</b>) <span class="html-italic">NF-κB</span> mRNA expression levels in liver samples. Data are exemplified as mean ± SEM. Following a one-way ANOVA test, the significant divisions among groups were analyzed using the Tukey–Kramar test, where ### <span class="html-italic">p</span> &lt; 0.001, contrasted with sham control; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP group; <span>$</span> <span class="html-italic">p</span> &lt; 0.05 and <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01, contrasted with CLP + Neb4 group.</p>
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<p>Effect of Nebivolol on p-AKT, p-JNK1/2, and p-p38 protein expressions. (<b>a</b>) Representative western blot membranes of t-AKT, p-AKT, t-JNK1/2, p-JNK1/2, t-p38, p-p38, and b-actin proteins for all studied groups; (<b>b</b>–<b>d</b>) expressions of p-AKT/t-AKT, p-JNK1/2/t-JNK1/2, and p-p38/t-p38 proteins were expressed densitometrically using bands in (<b>a</b>). Data are exemplified as mean ± SEM. Following a one-way ANOVA test, the significant divisions among groups were analyzed using the Tukey–Kramar test, where ### <span class="html-italic">p</span>&lt; 0.001, contrasted with sham control; ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001, contrasted with CLP group; <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01, contrasted with CLP + Neb4 group.</p>
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<p>Impact of Nebivolol on liver histological alterations. The figure demonstrates photographs of rat liver (H&amp;E staining, 400×). (<b>a</b>) Sham specimens depict a standard hepatic architecture, with hepatocytes organized in cords extending from the central vein (black arrow) and portal tract (blue arrow). (<b>b</b>) Nebivolol 10 group with the same structure as a sham group. (<b>c1</b>) CLP group showing hepatocyte necrosis, ballooning, and inflammatory cell infiltration (in the circle) with a higher magnification photomicrograph in (<b>c2</b>) (600×) showing binuclear cells (red arrow) with area of necrosis (brown arrow). (<b>d</b>) CLP/Nebivolol 4 showing decreased the inflammatory cell infiltration, ballooning deterioration, and hepatocyte necrosis (in the circle). (<b>e</b>) CLP/Nebivolol 10 improves the hepatic integrity with minimal inflammatory cells, slight centrilobular hepatocyte deterioration and ballooning with no necrosis. (<b>f</b>) CLP/vitamin C showing mild portal tract inflammation.</p>
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<p>Schematic illustration of the research design.</p>
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20 pages, 7707 KiB  
Article
Echinacoside Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease by Inhibiting Ferroptosis via Nrf2/HMOX1 Pathway
by Yiming Yan, Ningxi Yang, Fanglin Qin and Yarong Hao
Biomedicines 2024, 12(12), 2728; https://doi.org/10.3390/biomedicines12122728 - 28 Nov 2024
Viewed by 428
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic lipid accumulation, and echinacoside (ECH) has demonstrated antioxidant and anti-inflammatory effects across multiple conditions, it has demonstrated hepatoprotective effects. Ferroptosis represents a novel mechanism of cell demise, differing [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic lipid accumulation, and echinacoside (ECH) has demonstrated antioxidant and anti-inflammatory effects across multiple conditions, it has demonstrated hepatoprotective effects. Ferroptosis represents a novel mechanism of cell demise, differing from apoptosis and autophagy. Emerging research indicates that ferroptosis in hepatocytes plays a role in the development of alcoholic liver disease. This study aimed to reveal the effect and potential mechanism of ECH on MASLD. Methods: The effect of ECH on the viability, lipid deposition, lipid peroxidation, mitochondrial of OA/PA-treated HepG2 cells were evaluated by Cell Counting Kit-8 assay, JC-1 and immunofluorescence assay. Meanwhile, the mechanism of ECH was assessed using transmission electron microscopy and immunofluorescence analysis. Moreover, db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Body weight, lipids, and liver function were measured. liver pathology was performed. The mechanism of ECH in vivo was analyzed using Western blot and immunofluorescence analysis in db/db mice. Results: ECH attenuated lipid deposition, lipid peroxidation and ferroptosis induced by OA/PA in HepG2 cells. Mitochondrial morphology and function in HepG2 cells were also preserved by ECH. In db/db mice model of MASLD, ECH markedly ameliorated liver hepatocellular ballooning, inflammatory cell infiltration in the portal area, and fibrous tissue proliferation. ECH also increased the expression of Nrf2, HMOX-1, SLC7A11, and GPX4, and decreased the expression of ACSL4 in liver tissues. Mechanically, ECH repressed ferroptosis by activating the Nrf2/HO-1 signaling pathway. Conclusions: Our research revealed that ECH has the capability to modulate ferroptosis via the Nrf2-HMOX1pathway, consequently mitigating the progression of MASLD. This suggests that ECH has a potential role in the treatment of MASLD. Full article
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<p>Effect of ECH on cell viability. (<b>A</b>) Molecular structure of echinacoside (ECH). (<b>B</b>) The effects of different concentrations of ECH (0, 25, 50, 100, 200, 400 μM) on HepG2 cell viability. (<b>C</b>) The effect of ECH (0, 50, 100, 200, 400 μM) on the viability of HepG2 cells with or without OA/PA (150/75 μM/mL). Significance: ns, <span class="html-italic">p</span> ≥ 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Fer-1 and ECH alleviate lipid deposition and lipid peroxidation caused by OA/PA. (<b>A</b>) Oil red O staining (400×, scale = 50 μm). (<b>B</b>) The immunofluorescence staining of ROS (400×, scale = 50 μm). The red fluorescence intensity reflects the protein expression level of ROS. (<b>C</b>) Measurement of the average area of fat droplets. (<b>D</b>) ROS fluorescence scale. Significance: ns, <span class="html-italic">p</span> ≥ 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Effects of Fer-1 and ECH on mitochondria of HepG2 cells under OA/PA. (<b>A</b>) Monitoring of mitochondrial membrane potential by JC-1 staining (400×, scale = 50 μm). The ratio of red/green fluorescence indicates the degree of mitochondrial damage. (<b>B</b>) Fluorometric scale of JC-1 (J-a indicates JC-1aggregates, J-m indicates JC-1monomers). (<b>C</b>) Relative fluorescence intensity (aggregates/monomers) of JC-1. Significance: **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Mitochondrial changes in HepG2 cells treated with the indicated concentrations of Fer-1 and ECH. The ultrastructures of mitochondria were observed by transmission electron microscopy (the first row: 7.0k×, scale = 2 μm; the second row: 15.0k×, scale = 1 μm). Mitochondrial shrinkage, reduced or disappeared mitochondrial cristae, and ruptured outer mitochondrial membrane were observed in OA/PA-treated HepG2 cells. Red arrows point to mitochondria.</p>
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<p>Fer-1 and ECH inhibits OA/ PA-induced ferroptosis by affecting the expression of signaling pathway proteins in HepG2 cells. (<b>A</b>) The total expression level of GPX4 in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The green fluorescence intensity reflected the expression level of GPX4 protein. The blue fluorescence reflects nuclear (DAPI is a DNA-specific probe). (<b>B</b>) The total expression level of Nrf2 in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The expression level of Nrf2 protein was reflected by red fluorescence intensity. The blue fluorescence reflects nuclear. (<b>C</b>) The total expression level of ACSL4 in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The red fluorescence intensity reflected the expression level of ACSL4 protein. The blue fluorescence reflects nuclear. (<b>D</b>–<b>F</b>) The contents of iron, GSH, and MDA in the cells were determined by the corresponding detection kit. Significance: *, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>ML385 impacts the inhibitory effect of ECH on ferroptosis in HepG2 cells. (<b>A</b>) The total expression level of Nrf2 in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The expression level of Nrf2 protein was reflected by red fluorescence intensity. The blue fluorescence reflects nuclear. (<b>B</b>) The total expression level of GPX4 in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The green fluorescence intensity reflected the expression level of GPX4 protein. The blue fluorescence reflects nuclear. (<b>C</b>) The total expression level of ROS in HepG2 cells was detected by immunofluorescence staining (400×, scale = 50 μm). The red fluorescence intensity reflected the expression level of ROS. The blue fluorescence reflects nuclear.</p>
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<p>ECH alleviated lipid metabolism disorders and impaired liver function in mouse models. (<b>A</b>–<b>D</b>) Serum HDL-C, LDL-C, TC, TG levels. (<b>E</b>,<b>F</b>) Serum ALT, AST levels. (<b>G</b>) Serum AST/ALT level. (<b>H</b>) Weight gain; circle = db/m group, rectangle = db/db group, triangle = db/db + ECH group. (<b>I</b>) FPG; circle = db/m group, rectangle = db/db group, triangle = db/db-ECH group. Significance: *, <span class="html-italic">p</span> &lt; 0.05; ***, <span class="html-italic">p</span> &lt; 0.001 vs. db/m; #, <span class="html-italic">p</span> &lt; 0.05; ##, <span class="html-italic">p</span> &lt; 0.01; ###, <span class="html-italic">p</span> &lt; 0.001 vs. db/db.</p>
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<p>Effects of ECH on liver morphology, lipid accumulation and collagen deposition in liver tissue. (<b>A</b>) HE staining of liver tissue (200×, scale = 50 μm). (<b>B</b>) Oil red O staining of liver tissue (200×, scale = 50 μm). (<b>C</b>) Masson staining of liver tissue (200×, scale = 50 μm). The red arrows pointing to the lipid droplet, the blue arrows pointing to inflammatory cells; the black arrows pointing to balloon-like degenerated cells; the yellow arrows pointing to fibrosis in perisinusoidal tissues.</p>
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<p>ECH inhibits ferroptosis by regulating the Nrf2/HMOX-1/SLC7A11/GPX4 signaling pathway in mouse liver tissue. (<b>A</b>) The total expression level of GPX4 in mouse liver tissues was detected by immunofluorescence staining (400×, scale = 50 μm). Red fluorescence intensity reflects GPX4 protein expression level. The blue fluorescence reflects nuclear. (<b>B</b>) The total expression level of COX2 in mouse liver tissues was detected by immunofluorescence staining (400×, scale = 50 μm). Red fluorescence intensity reflected the expression level of COX2 protein. The blue fluorescence reflects nuclear. (<b>C</b>) Western blot detected the protein expression levels of Nrf2, HMOX-1, SLC7A11, GPX4, and ACSL4. (<b>D</b>–<b>H</b>) Relative protein expression was measured by densitometry. GAPDH was used as internal control. Significance: *, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>The effect of echinacoside in HepG2 cells. ECH was observed to upregulate the levels of Nrf2 and its downstream HMOX-1, GPX4, and SLC7A11 while inhibiting the expression of ACSL4 in a MASLD cell model. The imbalance of redox reactions in MASLD was regulated through the Nrf2/HMOX-1/SLC7A11/GPX4 pathway, and the massive release of intracellular ROS was inhibited, which protected the mitochondria, inhibited lipid peroxidation of the cell membrane structure, and ultimately inhibited the occurrence of ferroptosis. ECH alleviates MASLD by inhibiting ferroptosis via the Nrf2/HMOX-1 pathway. The schematic diagram was drawn by figdraw.</p>
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19 pages, 8014 KiB  
Article
Hepatoprotective, Lipid-Lowering and Antioxidant Effects of Mangaba Powder (Hancornia speciosa) Administered to Rats Fed a High-Fat Diet
by Bernadete de Lourdes de Araújo Silva, Margarida Angélica da Silva Vasconcelos, Kamila Sabino Batista, Fabiane Rabelo da Costa Batista, Hassler Clementino Cavalcante, Lydiane de Lima Tavares Toscano, Alexandre Sérgio Silva, Aline Barbosa D’Oliveira, Adriano Francisco Alves and Jailane de Souza Aquino
Foods 2024, 13(23), 3773; https://doi.org/10.3390/foods13233773 - 25 Nov 2024
Viewed by 631
Abstract
The aim of this study was to evaluate the potential effects of administering mangaba powder on liver function and somatic, oxidative and lipid metabolism parameters in rats fed a high-fat diet. Prepared mangaba powder has important amounts of phenolic compounds, vitamin C, dietary [...] Read more.
The aim of this study was to evaluate the potential effects of administering mangaba powder on liver function and somatic, oxidative and lipid metabolism parameters in rats fed a high-fat diet. Prepared mangaba powder has important amounts of phenolic compounds, vitamin C, dietary fiber and oligosaccharides. A total of 32 adult Wistar rats were initially randomized into two groups for the biological assay: normal-fat (NF, n = 16) and high-fat (HF, n = 16) diets for 21 days. These rats were subsequently subdivided into four groups: NF (n = 8), HF (n = 8), normal-fat diet with mangaba powder administration (NFMG, n = 8) and high-fat diet with mangaba powder administration (HFMG, n = 8). The treatment with mangaba powder (400 mg/kg) lasted an additional 28 days. Compared to the HF rats, the HFMG rats showed an 8% reduction in the body mass index. Treatment with mangaba reduced the serum cholesterol by 18%, as well as the hepatic deposition of triacylglycerides by 26% and cholesterol by 25%, in addition to increasing bile acid synthesis by 77% in this organ. Mangaba powder consumption attenuated the degree of hepatic steatosis, reduced lipid peroxidation and increased the serum and hepatic antioxidant capacity in HFMG rats. These results show that the consumption of mangaba powder had lipid-lowering, hepatoprotective and antioxidant effects, especially in HFMG rats, which may be associated with an additive and synergistic action between the bioactive compounds present in the product. Full article
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<p>Dietary intake (<b>A</b>), energy intake (<b>B</b>), lipid intake (<b>C</b>), body weight (<b>D</b>) and areas under the curve (<b>E</b>–<b>H</b>) in rats fed normal- or high-fat diets and treated or not with mangaba powder. NF: rats fed a normal-fat diet (n = 8); NFMG: rats fed a normal-fat diet with administration mangaba (n = 8); HF: rats fed a high-fat diet (n = 8); HFMG: rats fed a high-fat diet with administration mangaba (n = 8). AUC, area under the curve; IBW, initial body weight. † significant difference compared with NF; ‡ significant difference compared with NFMG; § significant difference compared with HF. Values are median to the 25th–75th percentiles (Kruskal–Wallis test and Tukey’s post hoc test, <span class="html-italic">p</span> ≤ 0.05), n = 8.</p>
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<p>Final lipid profile (<b>A</b>–<b>E</b>), cardiovascular risk index (<b>F</b>–<b>H</b>) and transaminases (<b>I</b>,<b>J</b>) of rats fed normal- or high-fat diets after treatment with mangaba powder. NF: rats fed a normal-fat diet (n = 8); NFMG: rats fed a normal-fat diet with administration mangaba (n = 8); HF: rats fed a high-fat diet (n = 8); HFMG: rats fed a high-fat diet with administration mangaba (n = 8). AST, aspartate aminotransferases; ALT, alanine aminotransferases; TG, triacylglycerides; TC, total cholesterol; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein; HDL, high-density lipoprotein; IU, international unit. † significant difference compared with NF; ‡ significant difference compared with NFMG; § significant difference compared with HF. Values are median to the 25th–75th percentiles (Kruskal–Wallis test and Tukey’s post hoc test, <span class="html-italic">p</span> ≤ 0.05), n = 8.</p>
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<p>Histological analysis and morphometry of the liver, intestine and adipose tissue of rats fed normal- or high-fat diets after the treatment period with mangaba powder. (<b>A</b>): NF group (liver); (<b>B</b>): HF group (liver); (<b>C</b>): NFMG group (liver); (<b>D</b>): HFMG group (liver); (<b>E</b>): NF group (intestine); (<b>F</b>): HF group (intestine) (<b>G</b>): NFMG group (intestine); (<b>H</b>): HFMG group (intestine); (<b>I</b>): NF group (adipose tissue); (<b>J</b>): HF group (adipose tissue); (<b>K</b>): group NFMG group (adipose tissue); and (<b>L</b>): HFMG group (adipose tissue). Arrows indicate hepatocytes with clear cytoplasm and peripheral nuclei compatible with hepatic steatosis (<b>C</b>). Arrows indicate many mononuclear cells, such as macrophages and lymphocytes (<b>G</b>,<b>H</b>). Grade of steatosis (<b>M</b>); ADA, adipocyte area (<b>N</b>); ADN, adipocyte number (<b>O</b>). † significant difference compared with NF; ‡ significant difference compared with NFMG; § significant difference compared with HF. Values are median to the 25th–75th percentiles (Kruskal–Wallis test and Tukey’s post hoc test, <span class="html-italic">p</span> ≤ 0.05), n = 8.</p>
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31 pages, 4941 KiB  
Review
Comprehensive Review on Fruit of Terminalia chebula: Traditional Uses, Phytochemistry, Pharmacology, Toxicity, and Pharmacokinetics
by Changjian Wang, Hongfei Zhang, Xiangdong Wang, Xinyue Wang, Xinru Li, Cuiying Li, Yuefei Wang and Min Zhang
Molecules 2024, 29(23), 5547; https://doi.org/10.3390/molecules29235547 - 24 Nov 2024
Viewed by 1297
Abstract
Terminalia chebula Retz., known for its dried fruit, namely Chebulae Fructus, is a medicinal plant with a long-standing global reputation, which was initially recognized for its therapeutic properties during the Jin Dynasty. This review consolidates current knowledge on the traditional uses, phytochemistry, pharmacological [...] Read more.
Terminalia chebula Retz., known for its dried fruit, namely Chebulae Fructus, is a medicinal plant with a long-standing global reputation, which was initially recognized for its therapeutic properties during the Jin Dynasty. This review consolidates current knowledge on the traditional uses, phytochemistry, pharmacological properties, toxicity, and pharmacokinetics of Chebulae Fructus, highlighting its clinical significance and the promising therapeutic potential of its compounds. To date, studies have identified approximately 149 compounds within the plant, including tannins, phenolic acids, lignans, triterpenes, flavonoids, and volatiles. These compounds confer a broad spectrum of biological activities in vitro and in vivo, such as antioxidant, anti-inflammatory, antiviral, anticancer, antibacterial, hepatoprotective, nephroprotective, neuroprotective, and anti-diabetic, some of which are already integrated into clinical practice. However, despite substantial advancements, considerable gaps remain in understanding the complete mechanisms of action, pharmacokinetics, and safety profiles of its extracts and compounds. This paper advocates for enhanced focus on these areas to fully elucidate the therapeutic capacities and facilitate the clinical application of Chebulae Fructus. This comprehensive analysis not only reinforces the ethnopharmacological significance of Chebulae Fructus but also lays a foundation for future pharmacological explorations. Full article
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<p>A whole <span class="html-italic">Terminalia chebula</span> Retz. plant (<b>A</b>); <span class="html-italic">T. chebula</span> fruits (<b>B</b>); <span class="html-italic">T. chebula</span> dried fruits (<b>C</b>); and a <span class="html-italic">T. chebula</span> global distribution map of the world (<b>D</b>) (reprinted from <a href="https://www.gbif.org/species/3189388" target="_blank">https://www.gbif.org/species/3189388</a>, accessed on 1 October 2024).</p>
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<p>Structures of tannins from Chebulae Fructus.</p>
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<p>Structures of tannins from Chebulae Fructus.</p>
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<p>Structures of phenolic acids from Chebulae Fructus.</p>
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<p>Structures of lignans from Chebulae Fructus.</p>
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<p>Structures of triterpenoids from Chebulae Fructus.</p>
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<p>Structures of flavonoids from Chebulae Fructus.</p>
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<p>Structures of volatiles from Chebulae Fructus.</p>
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<p>Structures of other chemicals from Chebulae Fructus.</p>
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<p>The main pharmacological action of Chebulae Fructus (arrow ↓ means decrease, arrow ↑ means increase).</p>
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14 pages, 2370 KiB  
Article
Effect of Constant Illumination on the Morphofunctional State and Rhythmostasis of Rat Livers at Experimental Toxic Injury
by Sevil A. Grabeklis, Maria A. Kozlova, Lyudmila M. Mikhaleva, Alexander M. Dygai, Rositsa A. Vandysheva, Anna I. Anurkina and David A. Areshidze
Int. J. Mol. Sci. 2024, 25(22), 12476; https://doi.org/10.3390/ijms252212476 - 20 Nov 2024
Viewed by 555
Abstract
The effect of dark deprivation on the morphofunctional state and rhythmostasis of the liver under CCl4 toxic exposure has been studied. The relevance of this study is due to the fact that the hepatotoxic effect of carbon tetrachloride on the liver is [...] Read more.
The effect of dark deprivation on the morphofunctional state and rhythmostasis of the liver under CCl4 toxic exposure has been studied. The relevance of this study is due to the fact that the hepatotoxic effect of carbon tetrachloride on the liver is well studied, but there are very few data on the relationship between CCl4 intoxication and circadian biorhythms, and most of the studies consider the susceptibility of the organism in general and of the liver in particular to the influence of CCl4 in some separate periods of the rhythm, but not the influence of this chemical agent on the structure of the whole rhythm. In addition, earlier studies indicate that light disturbance causes certain changes in the morphofunctional state of the liver and the structure of the circadian rhythm of a number of parameters. As a result of this study, we found that the effect of CCl4 in conditions of prolonged dark deprivation causes more significant structural and functional changes in hepatocytes, as well as leading to significant changes in the circadian rhythms of a number of parameters, which was not observed in the action of CCl4 as a monofactor. We assume that the severity of structural and functional changes is due to the light-induced deficiency of melatonin, which has hepatoprotective properties. Thus, the mechanisms of CCl4 action on CRs under conditions of light regime violations leave a large number of questions requiring further study, including the role of melatonin in these processes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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<p>Liver of rats: (<b>A</b>) control group, hematoxylin and eosin, ×100; (<b>B</b>) control group, hematoxylin and eosin, ×400; (<b>C</b>) group I, hematoxylin and eosin, ×100; (<b>D</b>,<b>E</b>) group I, hematoxylin and eosin, ×400; (<b>F</b>) group II, hematoxylin and eosin, ×100; (<b>G</b>,<b>H</b>) group II, hematoxylin and eosin, ×400.</p>
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<p>Liver of rats: (<b>A</b>) control group, hematoxylin and eosin, ×100; (<b>B</b>) control group, hematoxylin and eosin, ×400; (<b>C</b>) group I, hematoxylin and eosin, ×100; (<b>D</b>,<b>E</b>) group I, hematoxylin and eosin, ×400; (<b>F</b>) group II, hematoxylin and eosin, ×100; (<b>G</b>,<b>H</b>) group II, hematoxylin and eosin, ×400.</p>
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<p>Results of ICH studies: (<b>A</b>) control group, <span class="html-italic">Ki-67</span>; (<b>B</b>) group I, <span class="html-italic">Ki-67</span>; (<b>C</b>) group II, <span class="html-italic">Ki-67</span>. It can be seen that single cells with reaction results are present in the field of view only in animals of the first experimental group. (<b>D</b>) Control group, <span class="html-italic">Per2</span>; (<b>E</b>) group I, <span class="html-italic">Per2</span>; (<b>F</b>) group II, <span class="html-italic">Per2</span>, ×400.</p>
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<p>Results of ICH studies: (<b>A</b>) control group, <span class="html-italic">Ki-67</span>; (<b>B</b>) group I, <span class="html-italic">Ki-67</span>; (<b>C</b>) group II, <span class="html-italic">Ki-67</span>. It can be seen that single cells with reaction results are present in the field of view only in animals of the first experimental group. (<b>D</b>) Control group, <span class="html-italic">Per2</span>; (<b>E</b>) group I, <span class="html-italic">Per2</span>; (<b>F</b>) group II, <span class="html-italic">Per2</span>, ×400.</p>
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43 pages, 1629 KiB  
Review
Research Progress on Sesquiterpenes from the Genus Ainsliaea
by Hui Zhang, Ru-Ru Sun, Ya-Feng Liu, Xin Guo, Chong-Long Li, Ze-Dong Nan and Zhi-Bo Jiang
Molecules 2024, 29(22), 5483; https://doi.org/10.3390/molecules29225483 - 20 Nov 2024
Viewed by 719
Abstract
Sesquiterpenes constitute the principal components of the genus Ainsliaea, encompassing guaiane, germacrane, eudesmane, and polymer sesquiterpene lactones types. These secondary metabolites exhibit diverse pharmacological activities, including antitumor, antibacterial, anti-inflammatory, antiviral, antioxidant, hepatoprotective, and neuroprotective effects. Through a comprehensive literature search of the [...] Read more.
Sesquiterpenes constitute the principal components of the genus Ainsliaea, encompassing guaiane, germacrane, eudesmane, and polymer sesquiterpene lactones types. These secondary metabolites exhibit diverse pharmacological activities, including antitumor, antibacterial, anti-inflammatory, antiviral, antioxidant, hepatoprotective, and neuroprotective effects. Through a comprehensive literature search of the Web of Science, PubMed, SciFinder, and CNKI databases, it was discovered that there are as many as 145 main sesquiterpenoids in the genus Ainsliaea. However, the nuclear magnetic resonance (NMR) data for the sesquiterpenes in this genus have not been systematically compiled and summarized. Therefore, this review aims to highlight the chemical structures, NMR data, and pharmacological activities of sesquiterpenes in Ainsliaea. By meticulously analyzing published scholarly literature, our goal is to provide a solid foundation for further exploration of new sesquiterpenes and extensive utilization of this genus. Full article
(This article belongs to the Section Photochemistry)
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<p>Chemical structures for compounds <bold>1</bold>–<bold>63</bold>.</p>
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<p>Chemical structures for compounds <bold>1</bold>–<bold>63</bold>.</p>
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<p>Chemical structures for compounds <bold>64</bold>–<bold>75</bold>.</p>
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<p>Chemical structures for compounds <bold>76</bold>–<bold>110</bold>.</p>
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<p>Chemical structures for compounds <bold>111</bold>–<bold>135</bold>.</p>
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<p>Chemical structures for compounds <bold>111</bold>–<bold>135</bold>.</p>
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<p>Chemical structures for compounds <bold>136</bold>–<bold>145</bold>.</p>
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