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

引用

Journal of Traditional Chinese Medicine 2023年第6期43卷 1092-1102页

作者： YIN Yixiao TANG Hao FANG Yi LIU Wei WANG Jun HU Yiyang PENG Jinghua Institute of Liver diseases Shuguang Hospital affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Key Laboratory of Liver and Kidney Diseases(Shanghai University of Traditional Chinese Medicine) Ministry of EducationShanghai 201203China Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shanghai 201203China Institute of Clinical Pharmacology Shuguang Hospital affiliated to Shanghai University of Traditional Chinese MedicineShanghai201203China

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.

关键词： non-alcoholic fatty liver disease vitamin A metabolism PPAR gamma cytokine-cytokine receptor interaction Sanren Tang

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