Suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from Farfarae flos in BV-2 microglial cells.
Activated microglia produce diverse neurotoxic factors such as nitric oxide (NO) and prostaglandin E(2) (PGE(2)) that may cause neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. From the EtOAc soluble fraction of Farfarae flos (Tussilago farfara), we purified tussilagone as a bioactive compound by monitoring the inhibitory potential of NO production in activated microglia through the purification procedures. Tussilagone showed dose-dependent inhibition of NO and PGE(2) production in LPS-activated microglia with IC(50) values of 8.67 microM and 14.1 microM, respectively. It suppressed the expression of protein and mRNA of inducible nitric oxide synthase and cyclooxygenase-2 through the inhibition of 1-kappaBalpha degradation and nuclear translocation of p65 subunit of NF-kappaB. Therefore tussilagone from Farfarae flos may have therapeutic potential in the treatment of neuro-inflammatory diseases through the inhibition of overproduction of NO and PGE(2).
Lim
Hyo Jin
HJ
College of Pharmacy, Sookmyung Women's University, Yongsan-Gu, Seoul, 140-742, Korea.
Lee
Hyun-Sun
HS
Ryu
Jae-Ha
JH
D021581:Active Transport, Cell Nucleus; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D031207:Tussilago
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D012717:Sesquiterpenes; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C054337:tussilagone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone