AUTHOR=Teka Tekleab , Wu Jiang , Oduro Patrick Kwabena , Li Ze , Wang Chenxi , Chen Hao , Zhang Lin , Wang Haitao , Wang Liming , Han Lifeng TITLE=Integrated multi-omics analyses combined with western blotting discovered that cis-TSG alleviated liver injury via modulating lipid metabolism JOURNAL=Frontiers in Pharmacology VOLUME=Volume 15 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1485035 DOI=10.3389/fphar.2024.1485035 ISSN=1663-9812 ABSTRACT=Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects, necessitating detailed investigations into its bioactive components, particularly the stilbene glycosides, responsible for this duality effect. This study examined the pharmacological effects of cis-TSG, a stilbene glycoside, on ANIT-induced cholestasis in C57BL/6J mice. ANIT administration led to significant liver injury, as indicated by elevated ALT and AST levels and disrupted lipid metabolism. cis-TSG treatment significantly reduced ALT and AST levels, restored normal lipid profiles, and mitigated histological liver damage. Metabolomic and lipidomic analyses revealed that cis-TSG modulated key metabolic pathways, including glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis.Notably, cis-TSG increased levels of MUFAs and PUFAs, enhancing PPARĪ± activation, which contributed to its hepatoprotective effects. Transcriptomic analysis supported these findings, showing downregulation of genes involved in lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. These results suggest that cis-TSG mitigates ANIT-induced cholestasis through the modulation of lipid metabolism and activation of PPARĪ±. Our findings provide new insights into the therapeutic potential of cis-TSG for liver diseases and underscore the need for further research to fully elucidate its mechanisms of action.