Table_2_A systematic study of traditional Chinese medicine treating hepatitis B virus-related hepatocellular carcinoma based on target-driven reverse network pharmacology.xlsx

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）是全球范围内一项严重的公共卫生问题，乙型肝炎病毒（HBV）感染是其主要诱因。对于与HBV相关的HCC患者，标准治疗方案包括抗病毒治疗与同步抗癌治疗。然而，一种同时抑制HBV感染和HCC的药物尚未被发现。此外，药物耐药性和副作用使得现有的治疗方案效果不尽如人意。在应对多因素HBV感染和HCC方面，传统中医药（TCM）凭借其多成分、多靶点的优势，长期以来一直是发现新药的重要源泉和灵感来源。在本研究中，首次将目标驱动的反向网络药理学应用于系统地研究TCM治疗与HBV相关的HCC的潜在疗效。首先，筛选出47个HBV与HCC共有的靶点作为与HBV相关的HCC靶点。接着，从这47个靶点出发，匹配相关的化学成分和草药。构建了一个包含47个靶点、913个化学成分和469种草药的网络。随后，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所有草药都包含在469种草药中。进一步地，通过功能分析，理解了由这47个靶点调控的生物学过程和通路。对接结果显示，前50个化学成分与靶点结合良好。最后，频率统计分析结果表明，针对与HBV相关的HCC的469种草药主要具有温性、苦味，并分布于肝经。综合来看，通过目标驱动的方法，获得了一小库包含913个化学成分和469种草药，为开发治疗与HBV相关的HCC的治疗方法铺平了道路。