Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality, often driven by the over expression of oncogenes like TGFBR1. This study investigates the anti-cancer potential of flavonoids—Isorhamnetin and Kaempferol—extracted from Dendrophthoe falcata, a semi-parasitic medicinal plant. Soxhlet extraction followed by LC-MS identified 21 flavonoids. In-vitro assays on HEPG2 cells revealed significant Cytotoxicity (IC₅₀ = 89.76 µg/mL) and 83.11% apoptosis induction. In-silico analyses, including protein–protein interaction networks, gene ontology, and pathway enrichment, confirmed TGFBR1’s role in angiogenesis and apoptosis evasion. Five ADMET-compliant flavonoids were docked with TGFBR1, with Isorhamnetin showing the highest affinity. A dual-flavonoid approach combining Isorhamnetin and Kaempferol exhibited enhanced binding energy (-8.9 kcal/mol) and dynamic stability. Molecular dynamics simulations revealed complex stability with RMSD of 0.36 nm, reduced radius of gyration (2.05 to 1.98 nm), and lower solvent-accessible surface area (160 to 140 nm²). These findings suggest the synergistic flavonoid combination from D. falcata as a promising therapeutic strategy for HCC, warranting further preclinical validation.
Valarmathy et al. (Thu,) studied this question.