Revealing the active ingredients and mechanisms of Xiatianwu against hepatocellular carcinoma: a study based on network pharmacology and bioinformatics

Xiatianwu is a traditional Chinese medicine. This study investigates the function of Xiatianwu in treating HCC through database analyses and in vitro experiments. The active ingredients of Xiatianwu were identified from TCMSP and HERB databases and their targets were predicted by Swiss TargetPrediction. The HCC dataset was screened using the GEO database, and the differentially expressed genes between HCC and non-tumor liver tissues were analyzed to identify overlapping targets with Xiatianwu. The intersecting targets underwent enrichment analysis using R software to elucidate the molecular mechanisms of Xiatianwu against HCC. Core targets were identified using the PPI network and MCODE algorithm. Clinical relevance and disease prognosis in HCC were verified using the TCGA database. Meanwhile, binding affinities among components and targets were validated with molecular docking. Finally, the anti-HCC efficacy of the active ingredient was validated in vitro. Our findings revealed that eight active ingredients of Xiatianwu interacted with 11 key targets, providing anti-HCC efficacy. Molecular docking indicated that bicuculline and fumarine exhibited superior binding abilities. Bicuculline, a representative ingredient of Xiatianwu, was chosen for in vitro validation. Results demonstrated that bicuculline, in a dose-dependent manner inhibited HCC cell viability, reduced migration, suppressed the G0/M cell cycle, and decreased core protein expression. Xiatianwu demonstrates significant potential for clinical application in treating HCC. Bicuculline, a key active ingredient of Xiatianwu, exerts anti-HCC effects by inhibiting the cell cycle.