Department of Neurosurgery, Second Hospital of Shanxi Medical University, Taiyuan, China.
Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, China.
Front Cell Infect Microbiol. 2022 Aug 15;12:964469. doi: 10.3389/fcimb.2022.964469. eCollection 2022.
Hepatocellular carcinoma (HCC) is a serious global health problem, and hepatitis B virus (HBV) infection remains the leading cause of HCC. It is standard care to administer antiviral treatment for HBV-related HCC patients with concurrent anti-cancer therapy. However, a drug with repressive effects on both HBV infection and HCC has not been discovered yet. In addition, drug resistance and side effects have made existing therapeutic regimens suboptimal. Traditional Chinese medicine (TCM) has multi-ingredient and multi-target advantages in dealing with multifactorial HBV infection and HCC. TCM has long been served as a valuable source and inspiration for discovering new drugs. In present study, a target-driven reverse network pharmacology was applied for the first time to systematically study the therapeutic potential of TCM in treating HBV-related HCC. Firstly, 47 shared targets between HBV and HCC were screened as HBV-related HCC targets. Next, starting from 47 targets, the relevant chemical components and herbs were matched. A network containing 47 targets, 913 chemical components and 469 herbs was established. Then, the validated results showed that almost 80% of the herbs listed in chronic hepatitis B guidelines and primary liver cancer guidelines were included in the 469 herbs. Furthermore, functional analysis was conducted to understand the biological processes and pathways regulated by these 47 targets. The docking results indicated that the top 50 chemical components bound well to targets. Finally, the frequency statistical analysis results showed the 469 herbs against HBV-related HCC were mainly warm in property, bitter in taste, and distributed to the liver meridians. Taken together, a small library of 913 chemical components and 469 herbs against HBV-related HCC were obtained with a target-driven approach, thus paving the way for the development of therapeutic modalities to treat HBV-related HCC.
肝细胞癌（HCC）是一个严重的全球健康问题，乙型肝炎病毒（HBV）感染仍然是 HCC 的主要原因。对于伴有抗癌治疗的 HBV 相关 HCC 患者，给予抗病毒治疗是标准护理。然而，尚未发现具有抑制 HBV 感染和 HCC 双重作用的药物。此外，耐药性和副作用使现有的治疗方案效果不佳。中药（TCM）在处理多因素 HBV 感染和 HCC 方面具有多成分、多靶点的优势。TCM 长期以来一直是发现新药的宝贵来源和灵感。在本研究中，首次应用靶向反向网络药理学系统研究了 TCM 治疗 HBV 相关 HCC 的治疗潜力。首先，筛选出 47 个 HBV 和 HCC 之间的共同靶点作为 HBV 相关 HCC 靶点。接下来，从 47 个靶点出发，匹配相关的化学组分和草药。建立了一个包含 47 个靶点、913 个化学组分和 469 种草药的网络。然后，验证结果表明，慢性乙型肝炎指南和原发性肝癌指南中列出的几乎 80%的草药都包含在 469 种草药中。此外，还进行了功能分析，以了解这些 47 个靶点调节的生物学过程和途径。对接结果表明，前 50 个化学组分与靶点结合良好。最后，频率统计分析结果表明，针对 HBV 相关 HCC 的 469 种草药主要是温性、苦味，分布于肝经。总之，采用靶向方法获得了针对 HBV 相关 HCC 的 913 种化学组分和 469 种草药的小文库，为开发治疗 HBV 相关 HCC 的治疗方法铺平了道路。
