Sequential activation of ERα-AMPKαsignaling by the flavonoid baicalin down-regulates viral HNF-dependent HBV replication  

作　　者：Yi-jun Niu Cheng-jie Xia Xin Ai Wei-ming Xu Xiao-tong Lin Ying-qi Zhu Hai-yan Zhu Xian Zeng Zhong-lian Cao Wei Zhou Hai Huang Xun-long Shi 

机构地区：[1]Department of Biological Medicines&Shanghai Engineering Research Center of Immunotherapeutics,Fudan University School of Pharmacy,Shanghai,201203,China [2]Department of Chemistry,Fudan University,Shanghai,201203,China

出　　处：《Acta Pharmacologica Sinica》2025年第3期653-661,共9页中国药理学报(英文版)

基　　金：supported by grants from the National Key Research and Development Program of China(No.2023YFC3503400);the National Nature Science Foundation of China(No.82074097);the Key Program of National Nature Science Foundation of China(No.82030113);Shanghai Science and Technology Funds(No.17ZR1401700);Shanghai Municipal Health Commission Project(No.201740200);Shanghai Engineering Research Center of Immunotherapeutics(No.19DZ2251400).

摘　　要：Baicalin(BA),a natural component found in many traditional Chinese medicines,exerts protective effects against several viruses.Although our previous studies have revealed that the anti-hepatitis B virus(anti-HBV)activity of BA depends on hepatocyte nuclear factor(HNF)signaling,the specific mechanisms remain unclear.The present study explored the potential signaling mechanisms involved in BA-mediated HBV suppression.Transcriptomic analysis suggested that BA significantly modulates the estrogen receptor(ER)and AMPK signaling pathways in HepG2 cells.The ER alpha(ERα)binding affinity of BA and its estrogen-like agonist activity were subsequently verified through molecular docking assays,BA-ERαaffinity detection experiments,ERαluciferase reporter gene assays,and qRT-PCR.ERαknockdown(shRNA)and AMPK inhibition(Compound C and doxorubicin[Dox])experiments revealed that the sequential activation of the ERα-LKB1-AMPK-HNF signaling axis is essential for the anti-HBV effects of BA.This study indicates that BA may trigger the ERα-AMPKα-HNF pathway to inhibit HBV replication,providing insights into its potential protective mechanisms against other viruses.

关 键 词：antiviral flavonoid BAICALIN hepatocyte nuclear factor hepatitis B virus ERa AMPKα 

分 类 号：R285[医药卫生—中药学]