Jaceidin Flavonoid Isolated from <i>Chiliadenus</i> <i>montanus</i> Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies
Sameh S. Elhady,
Enas E. Eltamany,
Amera E. Shaaban,
Alaa A. Bagalagel,
Yosra A. Muhammad,
Norhan M. El-Sayed,
Seif N. Ayyad,
Amal A. M. Ahmed,
Mohamed S. Elgawish,
Safwat A. Ahmed
Affiliations
Sameh S. Elhady
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Enas E. Eltamany
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt
Amera E. Shaaban
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt
Alaa A. Bagalagel
Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Yosra A. Muhammad
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Norhan M. El-Sayed
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt
Seif N. Ayyad
Department of Organic Chemistry, Faculty of Science, Damietta University, New Damietta 34511, Egypt
Amal A. M. Ahmed
Department of Cytology & Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
Mohamed S. Elgawish
Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
Safwat A. Ahmed
Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, 41522 Ismailia, Egypt
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.
