title: Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production.
abstract: 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%; 1.35 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.
authors: Department of Biotechnology, Zhengzhou University, Zhengzhou 450001, China. daiguifu@zzu.edu.cn
authors: Gui-Fu
authors: GF
authors: Dai
authors: Jin
authors: J
authors: Zhao
authors: Zhi-Wen
authors: ZW
authors: Jiang
authors: Li-Ping
authors: LP
authors: Zhu
authors: Hai-Wei
authors: HW
authors: Xu
authors: Wen-Yan
authors: WY
authors: Ma
authors: Xiao-Rang
authors: XR
authors: Chen
authors: Rui-Jing
authors: RJ
authors: Dong
authors: Wei-Yi
authors: WY
authors: Li
authors: Hong-Min
authors: HM
authors: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001597:Benzylidene Compounds; D015232:Dinoprostone / Q000096:biosynthesis*; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004427:Ear Diseases / Q000139:chemically induced / Q000188:drug therapy*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006099:Granuloma / Q000188:drug therapy; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D001597:Benzylidene Compounds; D004224:Diterpenes; D011083:Polycyclic Compounds; D014992:Xylenes; C451700:chlorobenzylidine; D009569:Nitric Oxide; C030419:andrographolide; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone