机构：[1]Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[2]Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China四川大学华西医院[3]Department of Forensic Pathology, Medical School of Basic and Forensic Sciences, Sichuan University, Chengdu 610041, China[4]Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico 87108, United States
Whether luteolin inhibits HBV replication has not been validated and the underlying mechanism of which has never been elucidated. In this study, we show that luteolin reduces HBV DNA replication in HepG2.2.15 cells. Luteolin effectively inhibited the expression of hepatocyte nuclear factor 4α (HNF4α) and its binding to the HBV promoters in HepG2.2.15 cells. While the extracellular signal-regulated kinase (ERK) was activated by luteolin, inhibition of ERK abolished luteolin-induced HNF4α suppression. Consistently, blocking ERK attenuated the anti-HBV activity of luteolin. In a HBV replication mouse model, luteolin decreased the levels of HBsAg, HBeAg, HBV DNA replication intermediates, and the HBsAg and HBcAg expression. Taken together, our results validated the anti-HBV activity of luteolin in both in vitro and in vivo studies and established a signaling cascade consisting of ERK and HNF4α for inhibition of HBV replication by luteolin, which may be exploited for clinical application of luteolin for anti-HBV therapy.
基金：
This study
was supported by the research grants from the National Natural
Science Foundation of China (No. 81101602) and National
Science and Technology Major Project (No.
2013ZX10002005).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
最新[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
第一作者：
第一作者机构：[1]Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China[2]Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
共同第一作者：
通讯作者：
通讯机构：[1]Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China[2]Division of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Bai Lang,Nong Yunhong,Shi Ying,et al.Luteolin Inhibits Hepatitis B Virus Replication through Extracellular Signal-Regulated Kinase-Mediated Down-Regulation of Hepatocyte Nuclear Factor 4α Expression.[J].Molecular pharmaceutics.2016,13(2):568-77.doi:10.1021/acs.molpharmaceut.5b00789.
APA：
Bai Lang,Nong Yunhong,Shi Ying,Liu Miao,Yan Libo...&Tang Hong.(2016).Luteolin Inhibits Hepatitis B Virus Replication through Extracellular Signal-Regulated Kinase-Mediated Down-Regulation of Hepatocyte Nuclear Factor 4α Expression..Molecular pharmaceutics,13,(2)
MLA：
Bai Lang,et al."Luteolin Inhibits Hepatitis B Virus Replication through Extracellular Signal-Regulated Kinase-Mediated Down-Regulation of Hepatocyte Nuclear Factor 4α Expression.".Molecular pharmaceutics 13..2(2016):568-77
