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

Abstract

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 PGE2, IL-1β 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-κB 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.

• Authors: Xian Wu, Mingyue Song, Kanyasiri Rakariyatham, Jinkai Zheng, Shanshan Guo, Zhonghai Tang, Shuangde Zhou, Hang Xiao
• Journal: Journal of functional foods (J Funct Foods) Vol. 19 Issue Pt A Pg. 278-287 (Dec 01 2015) ISSN: 1756-4646 [Print] Netherlands
• PMID: 26770275 (Publication Type: Journal Article)