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  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  6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE 2 production.