4--hydroxy-5-6-7-8-3--pentamethoxyflavone and Dermatitis

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.

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Cytokines; Dermatitis; Dermatitis, Contact; Ear; Edema; Flavones; Male; Matrix Metalloproteinase 9; Mice; Nitric Oxide Synthase Type II; Phosphatidylinositol 3-Kinases; Phosphorylation; Phytotherapy; Skin; Tetradecanoylphorbol Acetate