Integrative Network Pharmacology and Bulk RNA-Seq Unveil Berberine's Modulation of Mitochondrial Function and Oxidative Stress via SOD2 in Experimental Models of Ovarian Cancer

Abstract

Ovarian cancer (OC) remains a formidable gynecological malignancy with limited therapeutic options and substantial side effects associated with conventional treatments. Berberine (BBR), a natural isoquinoline alkaloid, has shown promising anti-cancer properties; however, its mechanisms of action in OC are not fully elucidated. In this study, an integrative approach is employed that combines network pharmacology, molecular docking, molecular dynamics stability analysis and bulk RNA sequencing (bulk RNA-seq) to identify OC-related targets of BBR. In vivo and in vitro experiments demonstrate that BBR significantly inhibited tumor growth and metastasis in a mouse peritoneal metastasis model. Moreover, it is further confirmed that BBR modulates the OC microenvironment under high-lipid conditions by activating Superoxide Dismutase2 (SOD2), reducing lipid metabolism, and decreasing Reactive Oxygen Superspecies (ROS) levels.