title: 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.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Kanyasiri
authors.initials: K
authors.lastname: Rakariyatham
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.|Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.|Department of Food Science and Nutrition, University of Jinan, Jinan, Shandong, P. R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Guo
authors.affiliation: College of Bioscience and Biotechnology, Human Agricultural University, Changsha, Hunan, P. R. China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Tang
authors.affiliation: College of Bioscience and Biotechnology, Human Agricultural University, Changsha, Hunan, P. R. China.
authors.forename: Shuangde
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.|College of Bioscience and Biotechnology, Human Agricultural University, Changsha, Hunan, P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
keywords: 4′-demethylnobiletin; AP-1; COX-2; NF-κB; Nrf2; anti-inflammation; iNOS; metabolites; nobiletin