Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism  

作　　者：Xiao-Li Mei Shu-Yi Wu Si-Lan Wu Xiao-Lin Luo Si-Xing Huang Rui Liu Zhe Qiang 

机构地区：[1]Department of Pharmacology and Toxicology,Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory,Chongqing Academy of Chinese Materia Medica,Chongqing 400061,China [2]College of Chinese Medicine,Chongqing College of Traditional Chinses Medicine,Chongqing 402760,China [3]Department of Oncology,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China [4]College of Pharmacy,Chongqing Medical University,Chongqing 400010,China

出　　处：《World Journal of Hepatology》2024年第7期1051-1066,共16页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by Chongqing Fundamental Research Funds,No.jbky20210001;Key Programs of Technological Innovation and Application Development of Chongqing,China,No.cstc2021jscx-dxwtBX0016;Natural Science Foundation of Chongqing,No.cstc2021jcyjmsxmX0793;Science and Technology Project in Social Livelihood of Bishan District,Chongqing,China,No.BSKJ0078 and No.BSKJ0075;Performance Incentive-oriented Project of Chongqing,No.jxjl20220007。

摘　　要：BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

关 键 词：Hepatic steatosis INFLAMMATION Sex hormone metabolism Male hormone Phosphatase and tensin homolog deleted on chromosome ten 

分 类 号：R575.5[医药卫生—消化系统]