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: Xian Wu, Mingyue Song, Kanyasiri Rakariyatham, Jinkai Zheng, Minqi Wang, Fei Xu, Zili Gao, Hang Xiao
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 51 Pg. 10921-7 (Dec 30 2015) ISSN: 1520-5118 [Electronic] United States
• PMID: 26651527 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 4'-demethylnobiletin
• Anti-Inflammatory Agents
• Cytokines
• Flavones
• nobiletin
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Phosphatidylinositol 3-Kinases
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Anti-Inflammatory Agents
• Cyclooxygenase 2 (analysis)
• Cytokines (analysis)
• Dermatitis
• Dermatitis, Contact (etiology, prevention & control)
• Ear
• Edema (chemically induced, prevention & control)
• Flavones (metabolism, therapeutic use)
• Male
• Matrix Metalloproteinase 9 (analysis)
• Mice
• Nitric Oxide Synthase Type II (analysis)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Phytotherapy
• Skin (chemistry)
• Tetradecanoylphorbol Acetate