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

Abstract

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,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 and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract 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.

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

“…At the moment, cancer is the second cause of mortality and morbidity worldwide [ 1 , 2 ]. It accounts for 9.6 million cases of deaths in 2018 as estimated by WHO [ 3 , 4 ].…”

“…Regrettably, resistance to various chemotherapies and a lack of drug selectivity and toxicity are also problematic. Hence, there is an increasing need for new treatment strategies and more effectual antineoplastic agents to combat malignant tumors [ 2 , 3 ].…”

“…Natural products are promising candidates as anticancer agents for being more available and less harmful [ 1 , 2 ]. Another possibility is the combination of existing chemotherapeutics with plant polyphenols [ 3 ].…”

“…Plant derived flavonoids have been validated to be efficient chemotherapeutic candidates against numerous cancers via modulation of apoptosis. The main mechanisms involved are the intrinsic and extrinsic activation of apoptotic proteins, and induction of DNA damage besides their interference with multiple signal transduction in the process of carcinogenesis and consequently obstruct proliferation, angiogenesis and metastasis [ 1 , 2 ].…”

New Antiproliferative Triflavanone from Thymelaea hirsuta—Isolation, Structure Elucidation and Molecular Docking Studies

“…In a continuing effort to discover bioactive metabolites from Egyptian plants [ 17 , 19 ], our group focused on the isolation of active constituents from the EtOAc fraction of the total MeOH extract from the whole T. hirsute plant. Different spectroscopic techniques were then used to identify the isolated compounds.…”