Hepatic transcriptome delineates the therapeutic effects of Sanren Tang(三仁汤)on high-fat diet-induced non-alcoholic fatty liver disease

OBJECTIVE:To evaluate the effects of Sanren Tang(SRT,三仁汤)on a high-fat diet(HFD)-induced non-alcoholic fatty liver disease(NAFLD)in mice and to investigate the hepatic transcriptome regulated by SRT.METHODS:The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry.The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks.Obeticholic acid was used as a control drug.Body weight,food intake,and homeostatic model assessment for insulin resistance(HOMA-IR)index were analysed.Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score(NAS).Serum alanine aminotransferase(ALT)and hepatic triglyceride(TG)levels were measured.Lipids in hepatocytes were visualised by Oil red staining.RNA-sequencing was performed to determine the transcriptome profile of the liver tissue.The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting.RESULTS:Four principal compounds were identified in the SRT:adenosine,amygdalin,luteoloside,and magnolol.SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice,and decreased HOMA-IR,NAS and ALT,and hepatic TG levels.Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously.Retinol metabolism,cytokine-cytokine receptor interaction,and peroxisome proliferator-activated receptor(PPAR)γsignalling were the top three SRT-regulated pathways in NAFLD.CONCLUSIONS:SRT significantly ameliorated HFD-induced NAFLD,which was correlated with the regulation of genes enriched in the retinol metabolism,cytokine-cytokine receptor interaction,and PPARγsignalling pathways.