{"title":"A Study on the Protective Impact of Resveratrol on Liver Damage in Rats with Obstructive Jaundice.","authors":"You-Long Chai, Hao-Nan Zhang, Yuan Gao, Di-Hua Li, Hui Zhang","doi":"10.2174/0113862073306667240606115002","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear.</p><p><strong>Methods: </strong>In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways.</p><p><strong>Results: </strong>The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway.</p><p><strong>Conclusion: </strong>In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073306667240606115002","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear.
Methods: In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways.
Results: The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway.
Conclusion: In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.
期刊介绍:
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.