Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs.
Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion.



In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance.



The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism.



BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBVrtM204V/rtLl80Mtransfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs.
Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: HHai3552@sina.cn.
Hai
H
Huang
Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433, China. Electronic address: zhouw@fudan.edu.cn.
Wei
W
Zhou
Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: haiyanzhu@fudan.edu.cn.
Haiyan
H
Zhu
Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: pzhou@shmu.edu.cn.
Pei
P
Zhou
Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: xunlongshi@fudan.edu.cn.
Xunlong
X
Shi
D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D004372:Ducks; D005419:Flavonoids / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D005419:Flavonoids; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D012367:RNA, Viral; C038044:baicalin; C413685:entecavir; D006147:Guanine
Anti-HBV; Baicalin; HBV RNAs; Hepatocyte nuclear factors; Nucleoside analog