Transcriptional regulation of iNOS and COX-2 by a novel compound from Curcuma comosa in lipopolysaccharide-induced microglial activation

• Published in: Neuroscience letters 2009-09, Vol.462 (2), p.171-175
• Main Authors: Thampithak, Anusorn, Jaisin, Yamaratee, Meesarapee, Benjawan, Chongthammakun, Sukumal, Piyachaturawat, Pawinee, Govitrapong, Piyarat, Supavilai, Porntip, Sanvarinda, Yupin
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Blotting, Western; Cells, Cultured; COX-2; Curcuma; Curcuma - chemistry; Curcuma comosa; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Dinoprostone - genetics; Dinoprostone - metabolism; Fundamental and applied biological sciences. Psychology; Immunoenzyme Techniques; iNOS; Lipopolysaccharides - pharmacology; Microglia; Microglia - drug effects; Microglia - metabolism; Nitric Oxide Synthase Type II - drug effects; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; PGE 2; Plant Extracts - pharmacology; Rats; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.06.094

Overproduction of pro-inflammatory mediators resulting from chronic activation of microglia has been implicated in many neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. In this study, we investigated the effects of (3 R) 1,7-diphenyl-(4 E,6 E)-4,6-heptadien-3-ol, or compound 049 on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-treated microglia. Compound 049 is a pure compound fractionated from the hexane extract of Curcuma comosa, an indigenous plant of Thailand traditionally used as an anti-inflammatory agent for the treatment of uterine inflammation. It was found that pretreatment of the highly aggressively proliferating immortalized (HAPI), rat microglial cell line, with compound 049, at the concentrations of 0.1, 0.5 and 1 μM significantly decreased LPS-induced NO and PGE 2 production in a concentration-dependent manner. Parallel to the decreases in NO and PGE 2 production was a reduction in the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) as measured by mRNA and protein levels. These results indicate that compound 049 possesses an anti-inflammatory activity and may have a therapeutic potential for the treatment of neurodegenerative diseases related to microglial activation.