Inhibitory Effects of 4 '-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears

文献类型： 外文期刊

第一作者： Wu, Xian

作者： Wu, Xian;Song, Mingyue;Rakariyatham, Kanyasiri;Zheng, Jinkai;Wang, Minqi;Xu, Fei;Gao, Zili;Xiao, Hang;Xiao, Hang;Zheng, Jinkai

作者机构：

关键词： 4 '-demethylnobiletin;nobiletin;anti-inflammatory;12-O-tetradecanoylphorbol-13-acetate;ear edema

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.279； 五年影响因子：5.269 ）

ISSN：

年卷期：

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收录情况： SCI

摘要： 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-1 beta, IL-6, and TNF-alpha. 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.

分类号： R15`S

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