Search Results (3,416)

Lutjanus erythropterus protein (Lep) exhibits anti-inflammatory effects, but its antidepressant activity is unknown. This study used a 44-day chronic unpredictable mild stress (CUMS) model to determine whether Lep has a beneficial effect through the gut–brain axis in 3-week-old male C57BL/6 mice. Gavaging with Lep solution alleviated the depression-like behavior and anxiety symptoms in CUMS growing mice. Administration of Lep decreased serum IL-1β, IL-2, IL-6, and TNF-α levels and restored colonic mucosal damage. In addition, Lep improved the disturbance of 5-hydroxytryptamine (5-HT) secretion in the gut–brain axis. Pearson analysis revealed that gut short-chain fatty acid (SCFAs) concentration significantly (p < 0.05) correlated with mucosal damage scores and the depression-like behavior index. Lep was able to prevent the gut SCFA enrichment. Lep upregulated gut Muribaculaceae and downregulated SCFA-producing bacteria by replenishing deficient amino acid (AA) (tryptophan, alanine, aspartate, glutamate) and decreased (p < 0.01) the gene abundance of the AA metabolism pathway of SCFA-producing bacteria, thereby preventing gut SCFA enrichment and alleviating associated depression-like behavior. These findings indicate that Lep could attenuate depression in CUMS juvenile mice via the gut microbiota-SCFA–brain axis. Full article

Background: Gender differences in metabolic response to lifestyle interventions remain poorly explored. This study aimed to evaluate the impact of a six-month Mediterranean diet (MD) intervention combined with regular physical activity on metabolic parameters in overweight adults. Methods: A prospective cohort study was conducted in an obesity clinic in Rome, Italy, involving overweight adults (BMI ≥ 25 kg/m²) motivated to improve their lifestyle. Participants (n = 205; 107 men and 98 women) self-selected into physical activity groups (aerobic, anaerobic, combined or no activity). Gender-specific metabolic changes were assessed, including lipid profiles, liver markers and fasting glucose. Results: Significant gender differences in metabolic results were observed. Men showed greater reductions in total cholesterol (TC) and LDL, as well as significant reductions in alanine aminotransferase (ALT). Women showed a significant increase in HDL cholesterol. Fasting blood glucose decreased significantly in both sexes, with no differences between the sexes. Activity-specific analysis revealed that anaerobic activity significantly improved lipid metabolism in men, while aerobic activity produced the greatest benefits in women, including increased HDL and improved liver marker profiles. Conclusions: Therapeutic strategies combining MD and physical activity must take into account gender-specific physiological differences and the type of sport activity to optimise metabolic benefits. Personalised approaches may improve the management of cardiovascular risk factors in overweight individuals. Study registration: This study is registered on ClinicalTrials.gov (NCT06661330). Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. Methods: A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. Results: Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. Conclusions: The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes. Full article

Reduced glutathione (GSH) is a main nonenzymatic antioxidant, but its effects and underlying mechanisms on growth and intestinal health in weaned piglets still require further assessment. A total of 180 weaned piglets were randomly allotted to 5 groups: a basal diet (CON), and a basal diet supplemented with antibiotic chlortetracycline (ABX), 50 (GSH1), 65 (GSH2), or 100 mg/kg GSH (GSH3). Results revealed that dietary GSH1, GSH2, and ABX improved body weight and the average daily gain of weaned piglets, and ABX decreased albumin content but increased aspartate aminotransferase (AST) activity and the ratio of AST to alanine transaminase levels in plasma. GSH2 significantly decreased glucose content but increased the content of triglyceride and cholesterol in the plasma. Both GSH1 and GSH2 improved the jejunal mucosa architecture (villus height, crypt depth, and the ratio of villus height to crypt depth), tight junction protein (ZO-1 and Occludin), and antioxidant capacity (CAT and MDA), and the effects were superior to ABX. Dietary GSH improved the jejunal barrier by probably inhibiting the myosin light chain kinas pathway to up-regulate the transcript expression of tight junction protein (ZO-1 and Occludin) and Mucins. Through the proteomics analysis of the jejunal mucosa using 4D-DIA, the KEGG pathway enrichment analysis showed that differentiated proteins were significantly enriched in redox homeostasis-related pathways such as glutathione metabolism, cytochrome P450, the reactive oxygen species metabolic pathway, the oxidative phosphorylation pathway, and the phosphatidylinositol 3-kinase-serine/threonine kinase pathway in GSH2 vs. CON and in GSH2 vs. ABX. The results of proteomics and qRT-PCR showed that GSH supplementation might dose-dependently promote growth performance and that it alleviated the weaning stress-induced oxidative injury of the jejunal mucosa in piglets by activating SIRTI and Akt pathways to regulate GPX4, HSP70, FoxO1. Therefore, diets supplemented with 50–65 mg/kg GSH can promote the growth of and relieve intestinal oxidative injury in weaned piglets. Full article

As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf–MEK–ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners. It is still unclear how RKIP switches between monomeric and dimeric forms. Here, we identified the role of cysteine 133 in RKIP structural dynamics using recombinant human RKIP (rhRKIP) proteins purified from Escherichia coli BL21(DE3) cells. Mutation of alanine or serine instead of cysteine in RKIP proteins did not affect the biochemical characteristics, while dynamic light scattering and liquid chromatography (LC) quadrupole time-of-flight (Q-TOF) mass spectrometry (MS) suggested distinct peaks in solution, which were identified via LC–MS/MS analyses, and further clarified the role of cysteine in RKIP dimerization. rhRKIP dimer formation was abrogated by a 32-aa peptide mimicking the region between two RKIP proteins for dimerization. In addition, the 32-aa peptide and its short derivatives were investigated for effects on cancer cell viability. Taken together, our findings suggest that it may be possible to regulate RKIP function by controlling its dynamics with reducing agents, which could aid the targeting of cancer cells. Full article

Background/Objectives: With the improvement of living standards, alcoholic liver disease caused by long-term drinking has been a common multiple disease. Probiotic interventions may help mitigate liver damage caused by alcohol intake, but the mechanisms need more investigation. Methods: This study involved 70 long-term alcohol drinkers (18–65 years old, alcohol consumption ≥20 g/day, lasting for more than one year) who were randomly assigned to either the BC99 group or the placebo group. Two groups were given BC99 (3 g/day, 1 × 10¹⁰ CFU) or placebo (3 g/day) for 60 days, respectively. Before and after the intervention, blood routine indicators, liver function, renal function, inflammatory factors and intestinal flora were evaluated. Results: The results showed that intervention with Weizmannia coagulans BC99 reduced the levels of alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, serum total bilirubin, blood urea nitrogen, uric acid and ‘blood urea nitrogen/creatinine’. Weizmannia coagulans BC99 also reduced the levels of pro-inflammatory factors TNF-α and IL-6 and increased the levels of anti-inflammatory factor IL-10. The results of intestinal flora analysis showed that Weizmannia coagulans BC99 regulated the imbalance of intestinal flora, increased the beneficial bacteria abundance (Prevotella, Faecalibacterium and Roseburia) and reduced the conditionally pathogenic bacteria abundance (Escherichia-Shigella and Klebsiella). Both LEfSe analysis and random forest analysis indicated that the increase in the abundance of Muribaculaceae induced by BC99 was a key factor in alleviating alcohol-induced liver damage. Conclusions: These findings demonstrate that Weizmannia coagulans BC99 has the potential to alleviate alcoholic liver injury and provide an effective strategy for liver protection in long-term drinkers. Full article

This research examined the efficacy of substituting commercial fish meal (CFM) with Pterygoplichthys pardalis meal (PPM) in Hoplobatrachus chinensis diets, with and without Euphorbia hirta extract (EHE) supplementation. The study utilized six dietary treatments: a control diet (0% PPM, no EHE) and five experimental diets with varying PPM levels (0%+, 25%+, 50%+, 75%+, and 100%+), each fortified with 300 mg/kg EHE. The experiment spanned 90 days. The analysis revealed that PPM exhibited superior amino acid profiles compared to CFM, both in quality and quantity, while CFM demonstrated higher fatty acid content. The growth metrics showed a significant decline only in the group receiving 100% PPM replacement with EHE supplementation. Most organosomatic indices remained consistent across the treatments, with the exception of intraperitoneal fat, which decreased in all EHE-supplemented groups. Blood parameters, including white blood cells, red blood cells, and hematocrit, along with serum proteins (total protein, globulin, and albumin), displayed an upward trend in all EHE-supplemented groups. The 50%+ and 75%+ PPM replacement groups exhibited significantly elevated serum glucose levels (p < 0.05). Liver enzymes (alanine transaminase and aspartate transaminase) showed no significant variations among the treatments. The results indicate that PPM can serve as an effective replacement for up to 75% of CFM in H. chinensis feed, without compromising their growth performance. Moreover, supplementing with EHE helps to enhance essential biochemical indices in the body, without adversely affecting liver function. This investigation offers valuable perspectives on the development of sustainable aquaculture feed and the potential application of invasive fish species in aquatic animal nutrition. Full article

Bee venom (BV) and its main compound melittin (MLT) have antioxidant, anti-inflammatory, and anti-aging activities; however, very little research has been conducted on their effects on skin aging. In this study, a mouse skin aging model induced by D-galactose was constructed via subcutaneous injection into the scruff of the neck, and different doses of BV and MLT were used as interventions. The anti-aging effects and mechanisms of BV and MLT were explored by detecting the skin morphology and structure, and anti-aging-related factors and performing non-targeted metabolomics of mice. BV and MLT improved dermal and epidermal thickness, boosted the collagen fiber content, increased hydroxyproline and hyaluronic acid levels, and enhanced transcript-level expression of IL-10, Col1a1, and Col3a1, while decreasing that of IL-1β. Metabolomic analysis showed that BV and MLT regulated the levels of some metabolites (compared to those in the skin aging control). BV effectively alleviated skin aging by regulating the pentose phosphate pathway, and pathways associated with carbon, galactose, and β-alanine metabolism, whereas MLT regulated pathways related to lipid metabolism, cholesterol metabolism, and atherosclerosis. This study highlights the potential applicability of BV and MLT in skin aging treatments and cosmetic products. Full article

Coffee cherry pulp (CCP) is a by-product of coffee bean production. CCP contains amounts of phenolic compounds that are beneficial for animals. This study evaluated the impact of coffee cherry pulp extract (CCPE) supplementation on growth performance, meat quality, carcass characteristics, serum biochemistry, cecum microbial population, intestinal morphology, and immune and antioxidant responses of broilers. Five hundred 1-day-old Ross 308 chicks were randomly assigned to five groups: a basal diet control, a basal diet with antibiotic growth promoters at 0.25 g/kg, and groups supplemented with CCPE at 0.5, 1.0, and 2.0 g/kg diet over 35 days. The results showed that throughout the experimental period, the groups supplemented with CCPE improved their final weight, average daily gain, and feed conversion ratio (p < 0.05). CCPE at 1.0 and 2.0 g/kg diet reduced the average daily feed intake (p < 0.05). In addition, CCPE at 0.5 g/kg reduced levels of serum alanine transaminase and aspartate aminotransferase (p < 0.05). Triglyceride levels were the lowest in CCPE 2.0 (p < 0.05). In the group supplemented with CCPE at all levels, the high-density lipoprotein levels significantly increased (p < 0.05). Drip loss in the breast at 24 and 48 h decreased (p < 0.05). Additionally, live weight, defeathered weight, and carcass weight significantly increased (p < 0.05). Furthermore, CCPE improved intestinal morphology, especially villus height and the villus height per crypt depth ratio (p < 0.05). CCPE supplementation also reduced pathogenic bacteria, increased Lactobacillus spp. (p < 0.05), and increased the expression of immune-related genes and antioxidant activity in the liver and intestines (p < 0.05). Therefore, the use of CCPE as an alternative to antibiotics in broiler feed improved growth performance and health parameters in broilers. It provides a sustainable and environmentally friendly option for supplementary feed, contributing to more efficient poultry nutrition management. Full article

The aim of this study was to investigate the effects of different combinations of molasses levels and slow-release urea on Holstein fattening bulls. Sixty Holstein fattening bulls of a similar age, weight, and health status were randomly divided into four groups of fifteen Holstein fattening bulls each. All of the treatments were as follows: (1) basic diet group (CON); (2) 2% molasses slow-release urea group (LMU); (3) 4% molasses slow-release urea group (MMU); and (4) 6% molasses slow-release urea group (HMU). The results of the study showed that the MMU had an outstanding performance, with a 13.3% increase in average daily weight gain compared with the control group, a significant decrease in feed conversion ratio (p < 0.05), and a significant increase in apparent digestibility of crude protein (p < 0.05). In terms of serum biochemical indices, blood ammonia and alanine aminotransferase (ALT) concentrations were significantly higher in the MMU than in the CON (p < 0.05). The rumen pH of all treatment groups was lower than that of the CON (p < 0.05), whereas the concentrations of microbial crude protein (MCP), as well as acetic acid, propionic acid, and total volatile fatty acids (TVFA) were significantly higher in both the MMU and HMU (p < 0.05). The dominant phyla in each group were Bacteroidetes, Firmicutes, and Patescibacteria, and the relative abundance of Bacteroidetes in the MMU increased by 5.47% compared with that in the CON. In the MMU, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae increased by 9.03%, 0.67%, and 3.43%, respectively, compared with the CON. The economic benefit analysis showed that the daily feeding cost of fattened cattle in the MMU was reduced by RMB 1.62 yuan, and the daily farming benefit of each cow was increased by RMB 7.19 yuan. In conclusion, the MMU was effective in improving the growth performance of fattening cows, optimizing rumen fermentation, reducing cost, and increasing profit, which is a nutritional strategy with great application value. Full article

Background/Objectives: Liver injury is common after abdominal trauma. However, the established biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lack accuracy. This study investigates whether specific liver-related microRNAs (miRNAs) are released into the circulation in trauma patients with liver injury and whether they can indicate liver damage in the early phase after major trauma. Methods: A retrospective analysis of prospectively collected data and blood samples from 26 trauma patients was conducted. The levels of miRNA-21-5p, -122-5p, -191-5p, -192-3p, and -212-3p were measured in patients with computed tomography-confirmed liver trauma (LT group, n = 12) and polytrauma patients without liver trauma (PT group, n = 14) upon emergency room (ER) admission, and 24 and 48 h after trauma. Additionally, liver-type fatty acid binding protein (L-FABP) was measured, as it has recently been discussed in the context of abdominal trauma. Results: Only miRNA-122-5p showed a significant increase in the LT group compared to the PT group, but only at the 48 h time point (p = 0.032). Conversely, L-FABP (p = 0.018) and ALT (p = 0.05) were significantly elevated in the LT group compared to the PT group at the time of ER admission. There was a moderate correlation between miRNA-122-5p and AIS_Abdomen (p = 0.056) and transfused red blood cell concentrates (p = 0.055). L-FABP correlated strongly with the ALT levels (p = 0.0009) and the length of stay in the ICU (p = 0.0086). Conclusions: In this study, the liver-specific miRNA-122-5p did not effectively indicate liver injury in the early acute post-traumatic phase. Future research with a large sample size should investigate whether other miRNAs can more accurately predict liver injury and the extent of hepatocellular injury, particularly in the acute post-traumatic phase. Full article

Hazardous heavy metals, particularly cadmium (Cd), are widely distributed in the environment and cause oxidative stress in various animal and human organs. Clove oil (CLO), a common aromatic spice, has been used as a traditional medication as it has potent anti-inflammatory, antioxidant, and hepatoprotective properties. Background/Objectives: This study aimed to investigate the antioxidant, antiapoptotic, and anti-inflammatory effects of clove oil (CLO) against hepatorenal toxicity induced by cadmium (Cd). Methods: Twenty rats were equally divided into four groups: a control group, a Cd group treated with 15 mg/kg b.wt CdCl₂, a CLO group administered 200 mg/kg b.wt CLO, and a Cd+CLO group. All groups were orally treated for 4 weeks. Results: Cadmium (Cd) exposure caused anemia and hepatorenal damage, as evidenced by increased serum levels of urea, creatinine, uric acid, total bilirubin (including its direct and indirect fractions), and elevated activities of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). However, total protein and albumin levels decreased. Furthermore, there was a decrease in the levels of glutathione, glutathione transferase, and catalase in the liver antioxidant profiles. Meanwhile, malondialdehyde levels increased. Cadmium toxicity caused elevated expression of liver apoptosis markers, such as tumor necrosis factor-alpha (TNF-α) and caspase-3, and inflammation. CLO ameliorated the oxidative effects of Cd through decreasing urea (27.4%), creatinine (41.6%), liver enzymes, and hepatic apoptotic markers while increasing levels of total protein, albumin, and hepatic values of SOD (60.37%), CAT (64.49%), GSH (50.41%), and GST (9.16%). Conclusions: Hematological and biochemical parameters, as well as the antioxidant system, improved following clove oil treatment, leading to a reduction in hepatorenal damage. Therefore, it is possible to conclude that CLO protects rats from inflammation, apoptosis, and hepatorenal oxidative damage caused by Cd poisoning. Comprehensive translational research is required to validate CLO’s efficacy and safety of use in humans. Future studies should focus on elucidating the precise molecular mechanisms, optimal dosing strategies, and potential synergistic effects of CLO with other therapeutic agents. Full article

Background. We have previously reported peptides composed of sequential arginine (R) residues paired with tryptophan (W) or 3,3-diphenyl-L-alanine residues (Dip), such as cyclic peptides [R₄W₄] and [R₄(Dip)₃], as antibacterial agents. Results. Herein, we report antibacterial and antifungal activities of five linear peptides, namely ((DipR)₄(WR)), ((DipR)₃(WR)₂), ((DipR)₂(WR)₃), ((DipR)(WR)₄), and (DipR)₄R, and five cyclic peptides [(DipR)₄(WR)], [(DipR)₃(WR)₂], [(DipR)₂(WR)₃], [(DipR)(WR)₄], and [DipR]₅, containing alternate positively charged R and hydrophobic W and Dip residues against fungal, Gram-positive, and Gram-negative bacterial pathogens. The minimum inhibitory concentrations (MICs) of all peptides were determined by the micro-broth dilution method against Methicillin-Resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus subtilis. Fungal organisms were Candida albicans, Candida parapsilosis, and Aspergillus fumigatus. [DipR]₅ and ((DipR)₂(WR)₃) showed MIC values of 0.39–25 µM and 0.78–12.5 µM against Gram-positive and Gram-negative bacteria strains, respectively. The highest activity was observed against S. pneumoniae with MIC values of 0.39–0.78 µM among tested compounds. [DipR]₅ demonstrated MIC values of 6.6 µM against C. parapsilosis and 1.6 µM against A. fumigatus, whereas fluconazole showed MIC values of 3.3 µM and >209 µM, respectively. Conclusions. These findings highlight the potential of these peptides as broad-spectrum antimicrobial agents. Full article

Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. Methods: We aimed to characterize the pharmacokinetics of a licensed INH suspension (10 mg/mL, Pharmascience Inc., Montreal, QC, Canada) in children receiving INH daily at 10 mg/kg in a single-center, open-label, non-randomized, phase IIa clinical trial (EudraCT Number: 2016-002000-31) in Barcelona (Spain). Samples were analyzed using a validated UPLC-UV assay. The N-acetyltransferase 2 gene was examined to determine the acetylation status. A non-compartmental pharmacokinetic analysis was conducted. Results: Twenty-four patients (12 females) were included (primary chemoprophylaxis, n = 12; TB treatment, n = 9; and TB infection preventive treatment, n = 3). The acetylator statuses were homozygous fast (n = 3), heterozygous intermediate (n = 18), and homozygous slow (n = 2; unavailable in one patient). The INH median (IQR) C_max and AUC_0–24h values were 6.1 (4.5–8.2) mg/L and 23.0 (11.2–35.4) h∙mg/L; adult targets (>3 mg/L and 11.6–26.3 h∙mg/L) were not achieved in three and six cases, respectively. Gender, age at assessment (<2 or >2 years), and INH monotherapy (vs. combined TB treatment) had no impact on pharmacokinetic parameters. Significant differences in C_max (p = 0.030) and AUC_0–24h (p = 0.011) values were observed based on acetylator status. Treatment was well tolerated, and no severe adverse events were observed; three patients developed asymptomatic mildly elevated alanine aminotransferase levels. Conclusions: In infants and children receiving a daily INH suspension at 10 mg/kg, no safety concerns were raised, and the target adult levels were reached in the majority of patients. Full article

Background: Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as a key driver. The ethyl acetate extract of Cichorium glandulosum (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism of action against ALD remains unclear. This study investigates the effects and mechanisms of CGE in alleviating alcohol-induced oxidative stress and liver injury. Methods: Ultra-Performance Liquid Chromatography coupled with Quadrupole-Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap-MS) was used to identify CGE components. A C57BL/6J mouse model of ALD was established via daily oral ethanol (56%) for six weeks, with CGE treatment at low (100 mg/kg) and high doses (200 mg/kg). Silibinin (100 mg/kg) served as a positive control. Liver function markers, oxidative stress indicators, and inflammatory markers were assessed. Transcriptomic and network pharmacology analyses identified key genes and pathways, validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Results: UPLC-Q-Orbitrap-MS identified 81 CGE compounds, mainly including terpenoids, flavonoids, and phenylpropanoids. CGE significantly ameliorated liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and enhancing antioxidative markers such as total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) while lowering hepatic malondialdehyde (MDA) levels. Inflammation was mitigated through reduced levels of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1 Beta (IL-1β), and C-X-C Motif Chemokine Ligand 10 (CXCL-10). Transcriptomic and network pharmacology analysis revealed seven key antioxidant-related genes, including HMOX1, RSAD2, BCL6, CDKN1A, THBD, SLC2A4, and TGFβ3, validated by RT-qPCR. CGE activated the P21/Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) signaling axis, increasing P21, Nrf2, and HO-1 protein levels while suppressing Kelch-like ECH-associated Protein 1 (Keap1) expression. Conclusions: CGE mitigates oxidative stress and liver injury by activating the P21/Nrf2/HO-1 pathway and regulating antioxidant genes. Its hepatoprotective effects and multi-target mechanisms highlight CGE’s potential as a promising therapeutic candidate for ALD treatment. Full article