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

被引:57
作者
Chen, Shao-Rui [1 ]
Xu, Xiang-Zhen [1 ]
Wang, Yu-Hua [1 ]
Chen, Jian-Wen [1 ]
Xu, Suo-Wen [1 ]
Gu, Lian-Quan [2 ]
Liu, Pei-Qing [1 ]
机构
[1] Sun Yat Sen Univ, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Lab Bioorgan & Med Chem, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
关键词
icariin derivative; tumor necrosis factor-alpha; inducible nitric oxide synthase; cyclooxygenase-2; mitogen-activated protein kinase; nuclear factor-kappa B; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-INDUCED EXPRESSION; GENE-EXPRESSION; INTERFERON-GAMMA; IN-VITRO; MACROPHAGES; CYCLOOXYGENASE-2; INDUCTION; CELLS;
D O I
10.1248/bpb.33.1307
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In this study we investigated the anti-inflammatory effects of an icariin derivative (3,5-dihydroxy-4'-methoxy-6 '',6 ''-dimethyl-4 '',5 ''-dihydropyrano[2 '',3 '':7,8]-flavone). We found that this icariin derivative inhibits tumor necrosis factor-alpha (TNF-alpha) 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 (I kappa B alpha), and nuclear translocation of p65 subunit of nuclear factor (NF)-kappa B, and found it suppresses the activation of p38 MAPK and inhibits translocation of NF-kappa B p65 to the nucleus through decreasing the phosphorylation of I kappa B alpha. As a result of these properties, this icariin derivative can be considered as a potential drug for inflammatory diseases.
引用
收藏
页码:1307 / 1313
页数:7
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