5-O-Demethylnobiletin

5-O-Demethylnobiletin is a flavonoid that has been found in S. tragoriganum and has diverse biological activities.^1,2,3,4 It induces neurite outgrowth and the expression of the genes encoding the neuronal differentiation and synapse formation markers growth-associated protein 43 (GAP43) and synaptophysin in PC12 cells when used at concentrations ranging from 10 to 20 ?M.¹ 5-O-Demethylnobiletin (2.5-20 ?M) reduces triglyceride levels in 3T3-L1 preadipocytes and decreases body weight, intra-abdominal fat, plasma and liver triglyceride levels, and plasma cholesterol levels in a mouse model of high-fat diet-induced obesity when administered at a dose of 25 mg/kg.² It reduces hepatic fibrosis and malondialdehyde (MDA) levels in a mouse model of carbon tetrachloride-induced liver injury.³ 5-O-Demethylnobiletin also reduces ear edema, inflammatory cell infiltration, and papillar fibrosis in a mouse model of inflammation induced by phorbol 12-myristate 13-acetate .⁴

1.Chiu, S.-P., Wu, M.-J., Chen, P.-Y., et al.Neurotrophic action of 5-hydroxylated polymethoxyflavones: 5-demethylnobiletin and gardenin A stimulate neuritogenesis in PC12 cellsJ. Agric. Food Chem61(39)9453-9463(2013) 2.Tung, Y.-C., Li, S., Huang, Q., et al.5-Demethylnobiletin and 5-Acetoxy-6,7,8,3',4'-pentamethoxyflavone suppress lipid accumulation by activating the LKB1-AMPK pathway in 3T3-L1 preadipocytes and high fat diet-fed C57BL/6 miceJ. Agric. Food Chem64(16)3196-3205(2016) 3.Chang, S.N., Kim, S.H., Dey, D.K., et al.5-O-Demethylnobiletin alleviates CCL4-induced acute liver injury by equilibrating ROS-mediated apoptosis and autophagy inductionInt. J. Mol. Sci.22(3)1083(2021) 4.Bas, E., Recio, M.C., Giner, R.M., et al.Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganumPlanta Med.72(2)136-142(2006)