Icariin Derivative Inhibits Inflammation through Suppression of p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways

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In this study we investigated the anti-inflammatory effects of an icariin derivative (3,5-dihydroxy-4′-methoxy-6″,6″-dimethy1-4″,5″-dihydropyrano[2″,3″:7,8]-flavone). We found that this icariin derivative inhibits tumor necrosis factor-α (TNF-α) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression, and protein expression in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. It also alleviates paw edema induced by carrageenan in mice. To clarify the molecular mechanisms underlying these anti-inflammatory effects, we examined the effects of this compound on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphorylation of inhibitory kappaBalpha (IκBα), and nuclear translocation of p65 subunit of nuclear factor (NF)-κB, and found it suppresses the activation of p38 MAPK and inhibits translocation of NF-κB p65 to the nucleus through decreasing the phosphorylation of IκBα. As a result of these properties, this icariin derivative can be considered as a potential drug for inflammatory diseases.