Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production

被引:50
作者
Dai, Gui-Fu [1 ,2 ]
Zhao, Jin [1 ]
Jiang, Zhi-Wen [1 ]
Zhu, Li-Ping [1 ]
Xu, Hai-Wei [2 ]
Ma, Wen-Yan [1 ]
Chen, Xiao-Rang [2 ]
Dong, Rui-Jing [1 ]
Li, Wei-Yi [2 ]
Liu, Hong-Min [2 ]
机构
[1] Zhengzhou Univ, Dept Biotechnol, Zhengzhou 450001, Peoples R China
[2] Zhengzhou Univ, New Drug Res & Dev Ctr, Zhengzhou 450001, Peoples R China
基金
中国国家自然科学基金;
关键词
Andrographolide; Derivatives; Anti-inflammation; iNOS; PGE(2); FACTOR-KAPPA-B; NITRIC-OXIDE; IN-VITRO; PANICULATA; EXPRESSION; SUPPRESSION; CELLS;
D O I
10.1016/j.intimp.2011.09.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 135 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity. NO production, and PGE(2) production. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:2144 / 2149
页数:6
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