Targeting Colorectal Cancer With Helicteres isora L.: Integrative Approach Combining Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and In Vitro Validation

Helicteres isora L., a medicinal plant valued in traditional systems like Ayurveda and Chinese medicine, demonstrates significant therapeutic potential, particularly in colorectal cancer (CRC). This study evaluated its antioxidant and anticancer properties using 2,2-diphenyl-1-picrylhydrazyl and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assays, respectively. The methanolic fruit extract showed strong antioxidant capacity and moderate cytotoxicity against HCT-116 cells (half-maximal inhibitory concentration: 13.58 ± 1.12 µM). Systems biology approaches identified key oncogenic targets-ERBB2, epidermal growth factor receptor, MET, KRAS, TP53, and MAPK1-through network pharmacology and protein‒protein interaction analysis. Enrichment analysis linked its phytoconstituents with PI3K-Akt and MAPK pathways. Rosmarinic acid exhibited strong MAPK1 binding (‒8.754 kcal/mol), interacting with MET106, ASP109, and LYS52, with molecular dynamics simulations confirming stability. Survival analysis indicated that higher ERBB2 and MAPK1 expression correlated with improved outcomes, while receiver operating characteristic curves revealed moderate predictive value for chemotherapy response. These findings highlight H. isora as a promising source of anticancer agents, particularly targeting MAPK1, and support further exploration for CRC therapy.