Novel insights into the effect of Xiaoyao san on corticosterone-induced hepatic steatosis:inhibition of glucocorticoid receptor/perilipin-2 signaling pathway  

作　　者：Lian Gong Guo-En Wang Qing-Yu Ma Wen-Zhi Hao Min-Hua Xian Yan-Ping Wu Hiroshi Kurihara Rong-Rong He Jia-Xu Chen 

机构地区：[1]Formula-Pattern Research Center,School of Chinese Medicine,Jinan University,Guangzhou,China [2]Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility,Jinan University,Guangzhou,China [3]School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,China

出　　处：《Acupuncture and Herbal Medicine》2022年第1期49-57,共9页针灸和草药（英文）

基　　金：the National Natural Science Foundation of China(Nos.81630104 and 81622050).

摘　　要：Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknown.This study aimed to investigate whether XYS protects against corticosterone(CORT)-induced hepatic steatosis,and to explore its mechanism.Methods:High-fat diet mice induced with hepatic steatosis by 2mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks.The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids(triglyceride,total cholesterol,and free fatty acids).The mechanism of XYS against hepatic steatosis was investigated by network pharmacology,immunohistochemistry,western blotting,and gain-of-function/loss-offunction experiments.Results:XYS alleviated CORT-induced steatosis,decreased plasma lipids,and inhibited glucocorticoid receptor(GR)activation in the liver.Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein(ADFP).Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression.Conclusions:XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism.Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis,and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.

关 键 词：Adipose differentiation-related protein Glucocorticoid receptor Hepatic steatosis Network pharmacology Xiaoyao san 

分 类 号：R57[医药卫生—消化系统]