Jaceidin Flavonoid Isolated from Chiliadenusmontanus Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies

Phytochemical study ofChiliadenus montanusaerial parts afforded six compounds; Intermedeol (1), 5 alpha-hydroperoxy-beta-eudesmol (2), 5,7-dihydroxy-3,3',4'-trimethoxyflavone (3), 5,7,4'-trihydroxy-3,6,3'-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1 beta,4 beta,7 alpha-triol (5) and 1 beta,4 beta,7 beta,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin andC. montanusextract were evaluated for their in vivo anti-tumor activity against Ehrlich's ascites carcinoma (EAC). Compared to control group, jaceidin andC. montanusextract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.