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

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• 作者：Xian Wu ; Mingyue Song ; Kanyasiri Rakariyatham ; Jinkai Zheng ; Minqi Wang ; Fei Xu ; Zili Gao ; Hang Xiao
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2015
• 出版时间：December 30, 2015
• 年：2015
• 卷：63
• 期：51
• 页码：10921-10927
• 全文大小：331K
• ISSN：1520-5118

文摘

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.