扶正化瘀方及其活性成分通过促进HBV感染肝细胞TOMM34基因表

StephenW

扶正化瘀方及其活性成分通过促进HBV感染肝细胞TOMM34基因表达抑制HBeAg产生
陆兴 1 , 瑞增 2 , 黄开 1 , 景波学 ​​1 , 刘洪亮 1 , 赵志敏 1 , 袁鹏 1 , 胡旭东 2 , 刘澄海 1 3
隶属关系
隶属关系

    1
    【作者单位】： 上海中医药大学附属曙光医院肝病研究所;
    2
    上海中医药大学基础医学学院生物系，上海，中国。
    3
    上海市中医药临床医学重点实验室，上海，中国。

    PMID：36249820 PMCID：PMC9555080 DOI：10.3389/fphar.2022.907921

抽象的

背景与目的：扶正化瘀方（FZHY）是列入国家医保目录的中成药（批准文号：Z20020074），主要用于乙型肝炎病毒（HBV）所致肝纤维化的抗肝纤维化治疗和治疗。肝硬化。在临床实践中，我们发现 FZHY 也可能对抑制 HBeAg 产生具有直接的抗 HBV 作用，但其潜在机制尚不清楚。本研究旨在阐明FZHY抑制HBeAg产生的分子机制。方法：通过临床资料分析FZHY+恩替卡韦（ETV）组患者血清HBeAg滴度的下降程度。 C57BL/6N-Tg (1.28HBV)/Vst HBV转基因小鼠用于体内实验。 HepG2。 2.15细胞（野生型HBV复制细胞）用于体外实验。结果：临床研究结果显示，FZHY+ETV组治疗48周后血清HBeAg滴度下降程度明显高于ETV组。体内实验结果表明，FZHY可显着降低HBV转基因小鼠血清HBeAg滴度，促进HBeAg血清转换。体外实验结果表明，FZHY可以依赖性地降低HBeAg滴度，但对HBsAg和HBV-DNA的表达没有明显抑制作用。进一步的体外细胞实验发现，TOMM34 可能是 FZHY 抑制 HBeAg 产生的关键靶点。随后对FZHY中20种活性化合物的药理筛选实验表明，槲皮素、黄芩苷和虫草素可以促进TOMM34基因的表达，减少HBeAg的产生。结论：综上所述，FZHY及其活性化合物槲皮素、黄芩苷和虫草素可通过促进HBV感染肝细胞中TOMM34基因的表达来抑制HBeAg的产生。

关键词：扶正化瘀方；乙肝病毒； HBeAg; TOMM34;活性化合物。

版权所有 © 2022 Xing, Zeng, Huang, Xue, Liu, Zhao, Peng, Hu and Liu。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。

StephenW

Fuzheng Huayu Recipe and its active compounds inhibited HBeAg production by promoting TOMM34 gene expression in HBV-infected hepatocytes
Lu Xing  1 , Rui Zeng  2 , Kai Huang  1 , Jingbo Xue  1 , Hongliang Liu  1 , Zhimin Zhao  1 , Yuan Peng  1 , Xudong Hu  2 , Chenghai Liu  1   3
Affiliations
Affiliations

    1
    Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
    2
    Department of Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
    3
    Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China.

    PMID: 36249820 PMCID: PMC9555080 DOI: 10.3389/fphar.2022.907921

Abstract

Background and aim: Fuzheng Huayu Recipe (FZHY) is a Chinese patent medicine (approval No. Z20020074) included in the national medical insurance catalogue, which is mainly used for anti-hepatic fibrosis treatment of hepatitis B virus (HBV) induced liver fibrosis and liver cirrhosis. In clinical practice, we discovered that FZHY might also have a direct anti-HBV effect on inhibiting HBeAg production, but the mechanism underlying was unclear. This study aimed to clarify the molecular mechanism of the inhibition effect of FZHY on HBeAg production. Methods: The decrease degree of serum HBeAg titer in FZHY + entecavir (ETV) group patients were analyzed through clinical data. C57BL/6N-Tg (1.28HBV)/Vst HBV transgenic mice were used for in vivo experiments. HepG2. 2.15 cells (wild-type HBV replication cells) were used for in vitro experiments. Results: The clinical study results showed that the decrease degree of serum HBeAg titer in FZHY+ETV group was significantly higher than that in ETV group after 48 weeks treatment. In vivo experiments results showed that FZHY could significantly reduce the serum HBeAg titer in HBV transgenic mice, and promote HBeAg seroconversion. In vitro experiments results showed that FZHY could reduce HBeAg titer dependently, but it did not significantly inhibit the expression of HBsAg and HBV-DNA. Further cell experiments in vitro discovered that TOMM34 might be the key target for FZHY to inhibit HBeAg production. The subsequent pharmacological screening experiment of 20 active compounds in FZHY showed that quercetin, baicalin and cordycepin could promote the expression of TOMM34 gene and reduce the production of HBeAg. Conclusion: In conclusion, FZHY and its active compounds quercetin, baicalin and cordycepin could inhibit HBeAg production by promoting the expression of TOMM34 gene in HBV-infected hepatocytes.

Keywords: Fuzheng Huayu Recipe; HBV; HBeAg; TOMM34; active compounds.

Copyright © 2022 Xing, Zeng, Huang, Xue, Liu, Zhao, Peng, Hu and Liu.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

StephenW

https://www.frontiersin.org/arti ... har.2022.907921/pdf