The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Virology. 2021 Aug;560:66-75. doi: 10.1016/j.virol.2021.05.007. Epub 2021 May 22.
Current treatment methods for hepatitis B are mainly antiviral drug therapy and immunotherapy, in which antiviral drugs are mainly nucleoside analogue and interferon. They can significantly reduce the viral load but rarely achieve hepatitis B surface antigen (HBsAg) loss. 3,5,6,7,3',4'-Hexamethoxyflavone was screened out from a small molecule compound library for its lower cytotoxic effect and greater HBsAg inhibition activity. Meanwhile, we further performed experiments in HepG2.2.15, HepG2-NTCP cells, PHHs and HBV transgenic mouse model to evaluate the anti-HBV effects of 3,5,6,7,3',4'-Hexamethoxyflavone. Our study found that 3,5,6,7,3',4'-Hexamethoxyflavone can significantly reduce the level of HBV RNAs, HBV DNA and HBsAg, in addition, the activity of four HBV promoters and the ratio of total RNAs/cccDNA and 3.5 kb RNA/cccDNA were decreased by 3,5,6,7,3',4'-Hexamethoxyflavone. Mechanistically, we found HNF3α plays important roles in Hex mediated HBV transcription inhibition. Our study indicated Hex was a potential anti-HBV therapeutic drug.
目前乙型肝炎的治疗方法主要是抗病毒药物治疗和免疫治疗，其中抗病毒药物主要是核苷类似物和干扰素。它们可以显著降低病毒载量，但很少能实现乙型肝炎表面抗原（HBsAg）的丢失。3,5,6,7,3',4'-六甲氧基黄酮从小分子化合物库中筛选出来，因其细胞毒性较低，HBsAg 抑制活性较强。同时，我们还在 HepG2.2.15、HepG2-NTCP 细胞、PHHs 和 HBV 转基因小鼠模型中进一步进行了实验，以评估 3,5,6,7,3',4'-六甲氧基黄酮的抗 HBV 作用。我们的研究发现，3,5,6,7,3',4'-六甲氧基黄酮能显著降低 HBV RNAs、HBV DNA 和 HBsAg 的水平，此外，还能降低四个 HBV 启动子的活性，以及总 RNAs/cccDNA 和 3.5kb RNA/cccDNA 的比值。从机制上讲，我们发现 HNF3α 在 Hex 介导的 HBV 转录抑制中起重要作用。我们的研究表明，Hex 是一种有潜力的抗乙肝治疗药物。
