Schisanhenol ameliorates non-alcoholic fatty liver disease via inhibiting miR-802 activation of AMPK-mediated modulation of hepatic lipid metabolism  

作　　者：Bin Li Qi Xiao Hongmei Zhao Jianuo Zhang Chunyan Yang Yucen Zou Bengang Zhang Jiushi Liu Haitao Sun Haitao Liu 

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100193,China [2]Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Pathophysiology,Peking Union Medical College,Beijing 100005,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第9期3949-3963,共15页药学学报（英文版）

基　　金：National Natural Science Foundation of China(Nos.82304708 and U23A20511);the CAMS Innovation Fund for Medical Sciences(2023-I2M-QJ-013,2021-I2M-1-031,2022-I2M-2-002,and 2023-I2M-3-006,China);the Beijing Natural Science Foundation(No.Z220019,China).

摘　　要：Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease worldwide.Currently,satisfactory drugs for NAFLD treatment remain lacking.Obesity and diabetes are the leading causes of NAFLD,and compounds with anti-obesity and antidiabetic activities are considered suitable candidates for treating NAFLD.In this study,biochemical and histological assays revealed that a natural lignan schisanhenol(SAL)effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid(FFA)-treated HepG2 cells and high-fat diet(HFD)-induced NAFLD mice.Further,molecular analyses,microRNA(miRNA)-seq,and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphateactivated protein kinase(AMPK)pathway.Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated(p)-AMPK and PRKAB1.Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3’untranslated region of mouse Prkab1 or human PRKAA1.

关 键 词：SCHISANHENOL Non-alcoholic fatty liver disease Hepatic steatosis Lipid metabolism miR-802 AMPK SREBP-1C PPARa 

分 类 号：R589.2[医药卫生—内分泌]