A Study on the Protective Impact of Resveratrol on Liver Damage in Rats
with Obstructive Jaundice
Authors: Chai You-Long , Zhang Hao-Nan , Gao Yuan , Li Di-Hua , Zhang Hui 
Published: June 2024

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.