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

Abstract

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.

A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma with drugs based on bioinformatics and key target reverse network pharmacology and experimental verification

“…The liver was responsible for regulation and promotion. The lung was responsible for purification and descent [ 26 ]. The two organs complement each other to coordinate qi, blood and body fluid, and restore non-pathological state [ 27 ].…”

Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma

“…Interestingly, we found that these 306 targets were composed of 25 HCC targets and 281 non-HCC targets. Since TCM has the characteristics of multitarget pharmacological action, it can not only act on disease genes directly but also exert the therapeutic effect of HCC by acting on other related genes [ 24 , 45 ]. Figure 4(a) implies that most compounds are intensively linked to multiple targets.…”