Anti-inflammatory effect of methoxyflavonoids from Chiliadenus montanus (Jasonia Montana) growing in Egypt

Chiliadenus montanus is a medicinal plant that grows in Sinai Peninsula in Egypt. Phytochemical investigation of C. montanus methanolic extract led to the isolation of five methoxy flavonoids; Chrysosplenol-D (1), 5,7,4'-trihydroxy- 3,3'-dimethoxy flavone (2), 5,7-dihydroxy -3,3',4'-trimethoxyflavone (3), Bonanzin (4), 3,5,6,7,4'-pentamethoxy flavone (5), a sesquiterpene, Cryptomeridiol (6) and stigmast-5,22-dien-3-O-β-D-glucopyranoside (7). The anti-inflammatory activity of compounds 2 and 5 was assessed in vitro on CaCo2 cells stimulated by lipopolysaccharide (LPS). Both compounds downregulated LPS-induced expression of inflammatory cytokines; tumor necrosis factor alpha (TNFα), interleukin 1β (IL1β), nuclear factor kappa B (NFκB), cyclooxygenase 1 (Cox1), cyclooxygenase 2 (Cox2), and 5-lipoxygenase (5Lox). In vivo, both compounds significantly decreased paw edema thickness in rats relative to carrageenan, showing better anti-inflammatory activity than celecoxib (36.98%) after 1 h (46.60% and 48.11%, respectively). An in silico study was performed, where both compounds were docked into the active site of the crystal structure of the human Cox2 enzyme.