Elucidating the Multitarget Pharmacological Mechanisms of Berberine in Ovarian Cancer: An Integrated Network Pharmacology and Molecular Docking Study

Ovarian cancer (OC) is one of the most common causes of gynecological cancer mortality worldwide and is caused by late and advanced diagnosis, high metastatic potential, and resistance to most drugs. Multi-target therapeutic agents are urgently required, considering that OC is polygenic and heterogeneous. Berberine (BBR) is an isoquinoline alkaloid with anticancer, antiproliferative, and pro-apoptotic properties, making it a promising agent for OC treatment. In this study, an integrative network pharmacology and molecular docking method was used to identify the possible molecular targets and mechanistic pathways through which BBR exerts its therapeutic effects on OC. Four hundred and eighty-two putative BBR-associated genes were identified, of which 213 were associated with OC, and 35 were known to overlap with the targets. PPI network analysis showed that the 10 hub genes included EGFR, BCL2, AKT1, ESR1, CASP3, ERBB2, PTGS2, TNF, PIK3CA, and MDM2, with EGFR, AKT1, and ESR1 shortlisted as major regulatory nodes. GO and KEGG enrichment tests revealed a high level of participation of the BBR-target genes in cell survival, apoptosis, and cancer-associated signaling pathways, especially PI3K-Akt, MAPK, and hormone-regulated cascades. Molecular docking also revealed the high binding affinities of BBR with EGFR (-9.2 kcal/mol), AKT1 (-11.1 kcal/mol), and ESR1 (-7.6 kcal/mol), indicating stable and good interactions with the standard reference inhibitors. Overall, the results indicate that BBR has the potential to be a powerful multi-target agent that can regulate important oncogenic pathways in OC. This study offers a mechanistic model to be followed by additional in vitro, in vivo, and molecular dynamics validation and emphasizes the translational opportunities of BBR as an adjunct or as a sole therapeutic agent in the management of ovarian cancer.