ObjectiveLiver cancer is the 4^th leading cause of cancer death worldwide,and hepatocellular carcinoma (HCC) accounts for the largest proportion of these deaths. Berberine is a quaternary amine compound extracted from plants such as Coptidis Rhizoma (Huang Lian, 黄连) and Phellodendri Chinensis Cortex (Huang Bo, 黄柏) and is considered as a potential candidate for treating HCC. This study used network pharmacology methods, reveal the core mechanism of action of berberine in the treatment of HCC, clarify its medicinal value, and locate the anti-tumor mechanism of berberine.

MethodsStructural information of Berberine (PubChem CID: 2353) was obtained from the NCBI PubChem; ADME parameter were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database; Berberine prediction targets were collected from symmap, stitch and targetnet databases; HCC significant targets were retrieved from OncoDB.HCC and Liverome; A PPI network was established at STRING, Prediction target of berberine therapy for HCC are collected by gene mapping; The core target, pathway, biological process (BP), cellular component (CC), and molecular function (MF) of berberine in the treatment of HCC were predicted by topological analysis and enrichment analysis; the visualized "target pathway" network diagram of berberine in the treatment of HCC was established by the software of Cytoscape.

ResultsThrough PubChem and tcmsp databases, the good drug-forming properties of berberine were identified; 32 prediction targets of berberine were collected in symmap, stitch and targetnet databases; 566 related targets of HCC were collected in oncodb.hcc and liverome databases; 10 targets of berberine treatment for HCC were predicted by gene mapping, and a PPI with 10 nodes and 34 edges was established Through topological analysis and enrichment analysis, 6 topologically important targets, 6 related pathways and 16 BP, 6 cc and 7 MF involved in Berberine treatment of HCC were obtained.

ConclusionsThe anticancer effect of berberine is mainly involved in the regulation of cells of hepatoma cells through complex interactions between the TB52, MAPK1, CCND1, PTGS2, ESR1 that act on Hub nodes and their associated 6 pathways. The cycle is related to the immune inflammatory response, including biological processes such as proliferation and apoptosis of liver cancer cells.