Anti-inflammatory effects of 4 '-demethylnobiletin, a major metabolite of nobiletin

作者：Wu, Xian; Song, Mingyue; Rakariyatham, Kanyasiri; Zheng, Jinkai; Guo, Shanshan; Tang, Zhonghai; Zhou, Shuangde; Xiao, Hang^*

来源：Journal of Functional Foods, 2015, 19(Pt A): 278-287.

DOI：10.1016/j.jff.2015.09.035

• 4 '-Demethylnobiletin
• Nobiletin
• Anti-inflammation
• NF-kappa B
• Nrf2
• Metabolites

Nobiletin, a citrus flavonoid, has been associated with various beneficial biological activities. 4'-Demethylnobiletin (4DN) is a major metabolite of nobiletin, and its tissue level was found to be much higher than that of nobiletin after oral administration of nobiletin in mice. Anti-inflammatory effects of 4DN were studied in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The results showed 4DN not only dose-dependently inhibited LPS-induced nitric oxide production, but also significantly reduced expression of pro-inflammatory mediators, namely PGE(2), IL-1 beta and IL-6. 4DN potently suppressed the expression of iNOS and COX-2 at both protein and mRNA levels. 4DN also inhibited nuclear translocation of NF-kappa B and AP-1. Furthermore, we demonstrated that 4DN activated transcription factor Nrf2 and its dependent genes including HO-1 and NQO1 whose expression may contribute to anti-inflammatory effects. The results demonstrated anti-inflammatory effects of 4DN and provided a scientific basis for using nobiletin as a nutraceutical to inhibit inflammation-driven diseases.

• 出版日期2015-12
• 单位中国农业科学院; 湖南农业大学; 济南大学