Mechanistic study of Inonotus obliquus phenolic compounds in the treatment of liver cancer: A database and simulation approach

Inonotus obliquus is a large fungus with high phenolic content that has demonstrated promising potential for the treatment of liver cancer. However, studies investigating its mechanism of action in the treatment of liver cancer are scarce. To explore its mechanism of action, network pharmacology was used to collect phenolic compounds from I. obliquus, identify potential targets related to liver cancer, and examine their association with relevant signaling pathways. Moreover, molecular docking was conducted to explore the binding abilities between the phenolic compounds of I. obliquus and core targets. Finally, molecular dynamics simulations were performed to assess the binding stability of protein-ligand complexes. A total of 22 phenolic compounds were identified in I. obliquus in the CNKI database. The 10 core targets in the PPI network included VEGFA, CTNNB1, KDR, VAV3, VAV2, CDC42, TP53, CBL, CCND1 and CDK2, all of which were primarily related to tumor angiogenesis, invasion, migration and cell cycle. GO analysis yielded 1487 biological processes, 99 cellular components, and 207 molecular functions. Meanwhile, KEGG enrichment analysis identified 103 signaling pathways, of which the MAPK pathway had the most annotated targets. Additionally, the results of molecular docking indicated that phenolic compounds in I. obliquus could effectively bind to the 10 core targets in the PPI network, with the lowest overall binding energy observed for the target CDK2. Finally, the results of molecular dynamics simulation demonstrated that over 100 ns, the phenolic compounds in I. obliquus, namely hesperetin, quercetin, isorhamnetin-3-O-glucoside, and rutin, could stably bind to the target CDK2. Overall, these findings indicated that phenolic compounds in I. obliquus regulate the proliferative, migratory and invasive abilities of liver cancer cells through multiple targets and signaling pathways. This study provides a scientific reference for the development of I. obliquus phenolic compounds as therapeutic agents for liver cancer.