Analysis of the medication rules of traditional Chinese medicines (TCMs) in treating liver cancer and potential TCMs exploration

Liver cancer (LCa) is one of the most common malignancies. Western medicine is the main treatment strategy of LCa, but it has not achieved the ideal therapeutic effect. Traditional Chinese Medicines (TCMs) have a wide range of biological effects, lots of evidence suggests that they may kill tumors by regulating the tumor microenvironment and enhancing the immune system. The purpose of this research is to explore the medication rules of TCMs in treating LCa and excavate the potential TCMs for LCa. We combined genes associated with the MAPK, PI3K/Akt, and mTOR signaling pathways, as well as differentially expressed genes of LCa from the TCGA database, to determine 12 prospective core targets by building a prognostic model. We added 18 previously published LCa core targets to create a list of key targets. GO and KEGG analyses were used to validate the rationality of the key targets. The reliability of the corresponding relationships between targets and compounds was verified by molecular docking. The targets-compounds-herbs network was constructed and topologically analyzed to obtain potential herbs for LCa. The nature, flavor and meridian tropism of the herbs were analyzed to explore the rule of TCMs in the treatment of LCa. We obtained 30 potential targets including BRCA1, STMN1, MECOM, ITGB5 and SKP2. A total of 115 candidate compounds including resveratrol, quercetin, epigallocatechin gallate, estradiol and curcumin, and 1182 candidate herbs, including Jinyinhua, Gouguye, Tufuling, Huzhang, Jishiteng, Nvzhenzi, Sangbaipi and Qianhu were obtained. The vast majority of LCa's core targets, compounds and herbs we obtained have been verified by previous studies. Among the potential herbs, the categories of clearing heat and detoxifying, activating blood and dissolving stasis, and strengthening the spleen and benefiting the qi accounted for a high percentage. The herbs against LCa are mainly bitter, pungent, sweet in flavor, warm, cold, and mild in nature, and are mainly distributed in the liver, stomach, and lung meridians. Some of the potential herbs we obtained like Jinyinhua, Gouguye, Tufuling, Huzhang and Qianhu have been proved to be effective for LCa, while some of them like Jishiteng, Nvzhenzi and Sangbaipi have been shown to have a protective effect on the liver. The potential herbs have not been widely and deeply used and need to be further explored. The combination of network pharmacology and data mining provides novel approaches to the screening and exploitation of TCM.