title: Inhibitory Effects of 4'-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears.
abstract: Nobiletin (NOB) is major citrus flavonoid with many health-promoting benefits. We reported previously that 4'-demethylnobiletin (4DN), a major metabolite of NOB, significantly inhibited lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages. In this study, we further studied the anti-inflammatory effects of 4DN in TPA-induced skin inflammation in mice. We demonstrated that topical application of 4DN decreased TPA-induced ear edema by >88 ± 4.77% in mice. This inhibitory effect was associated with inhibition on TPA-induced up-regulation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Immunoblotting results showed that 4DN resulted in profound effects on multiple proteins related with inflammation and carcinogenesis. 4DN significantly decreased the expression levels of iNOS, COX-2, and MMP-9, suppressed phosphorylation of PI3K/Akt and ERK, and increased the levels of HO-1 and NQO1 in TPA-treated mice. Overall, the results demonstrated that 4DN had strong anti-inflammatory effects in vivo, which provided a scientific basis for using NOB to inhibit inflammation-driven diseases.
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Kanyasiri
authors.initials: K
authors.lastname: Rakariyatham
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.|Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences , Beijing, People's Republic of China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Minqi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.
authors.forename: Zili
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts, United States.|College of Bioscience and Biotechnology, Hunan Agricultural University , Changsha, Hunan, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2 / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003872:Dermatitis; D003877:Dermatitis, Contact / Q000209:etiology / Q000517:prevention & control*; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D047309:Flavones / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D012867:Skin / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate
chemical_list: C515881:4'-demethylnobiletin; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047309:Flavones; C008661:nobiletin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate
keywords: 12-O-tetradecanoylphorbol-13-acetate; 4′-demethylnobiletin; anti-inflammatory; ear edema; nobiletin