Transcriptional regulation of iNOS and COX-2 by a novel compound from Curcuma comosa in lipopolysaccharide-induced microglial activation.
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 (3R) 1,7-diphenyl-(4E,6E)-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 1microM 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.
Thampithak
Anusorn
A
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Jaisin
Yamaratee
Y
Meesarapee
Benjawan
B
Chongthammakun
Sukumal
S
Piyachaturawat
Pawinee
P
Govitrapong
Piyarat
P
Supavilai
Porntip
P
Sanvarinda
Yupin
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D030024:Curcuma / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010936:Plant Extracts; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D015232:Dinoprostone