(±)-Naringenin

(±)-Naringenin is an orally available anti-inflammatory agent that can regulate both acute and chronic inflammation responses, while also showing antioxidant, neuroprotective, liver-protective, and anti-cancer effects. (±)-Naringenin promotes vasodilation in endothelial cells by activating BK_Ca channels in muscle cells. It also exerts protective effects against experimental colitis by inhibiting Toll-like receptor 4/NF-κB signaling, making it useful in studies related to sepsis, fulminant hepatitis, fibrosis, and cancer research^[1][2][3]. In Vitro: (±)-Naringenin induces concentration-dependent relaxation in endothelium-denuded aortic rings from rats pre-contracted with 20 mM KCl or norepinephrine, with pIC₅₀ values of 4.74 and 4.68 respectively^[1].
(±)-Naringenin increases large conductance calcium-activated potassium (BKCa) current in rat tail artery smooth muscle cells in a concentration-dependent manner^[1].
(±)-Naringenin (1-25 μmol/L, 2 h) significantly inhibits TNF-α induced NF-κB luciferase expression in HT29 cells^[2].
(±)-Naringenin (25 μmol/L, 2 h) blocks LPS-induced NF-κB p65 nuclear translocation in mouse macrophage RAW264.7 cells^[2].
(±)-Naringenin induces apoptosis through both intrinsic (mitochondrial) and extrinsic pathways, upregulating pro-apoptotic genes such as P18, P21, p38, and Bcl-2-associated X protein (Bax), which stimulates mitochondrial cytochrome c release and forms apoptosomes including pro-caspase-9 and apoptosis protease-activating factor 1 (Apaf-1), thereby enhancing caspase-9 expression^[3]. In Vivo: (±)-Naringenin (50 mg/kg, orally, once a day for ten days) significantly reduces the severity of DSS-induced colitis in mice and downregulats pro-inflammatory mediators (iNOS, ICAM-1, MCP-1, Cox2, TNF-α, and IL-6 mRNA) in the colonic mucosa^[2].