Huang Hai, Zhou Wei, Zhu Haiyan, Zhou Pei, Shi Xunlong
Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433, China.
Toxicol Appl Pharmacol. 2017 May 15;323:36-43. doi: 10.1016/j.taap.2017.03.016. Epub 2017 Mar 18.
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 HBV transfected 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.
尽管目前用于慢性乙型肝炎病毒（HBV）感染的抗病毒治疗（核苷类似物，NAs）在抑制HBV-DNA复制方面有效，但其临床疗效可能会因耐药性增加和促进HBsAg/HBeAg血清学转换效率低下而受到影响。
在本研究中，我们将探讨一种天然产物黄芩苷（BA），其具有一线抗HBV药物恩替卡韦（ETV）的抗HBV疗效，对HBV-DNA、HBsAg/HBeAg血清学转换和耐药性的可能作用及机制。
在野生型/NA耐药突变型HBV细胞系和鸭乙肝病毒（DHBV）感染的雏鸭模型中研究BA和ETV的联合作用。探索HBV-DNA/RNA、HBsAg/HBeAg、宿主因子（肝细胞核因子）以寻找可能的抗HBV机制。
BA可显著增强并降低野生型HBV细胞系hepG2.2.15中的HBsAg和HBeAg。BA和ETV联合处理对NA耐药的HBV转染的hepG2细胞有更显著的作用。我们的研究进一步表明，BA主要抑制HBV RNA（3.5、2.4、2.1kb）的产生，HBV RNA是病毒蛋白和HBV-DNA合成的模板。BA可能通过下调依赖HBV复制的肝细胞核因子（HNF1α和HNF4α）的转录和表达来阻断HBV RNA转录。因此，BA可能通过抑制HBV病毒RNA而有利于抗HBV治疗。
