Potent inhibition of the inductions of inducible nitric oxide synthase and cyclooxygenase-2 by taiwaniaflavone.
The improper productions of nitric oxide and prostaglandins following the inductions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are involved in the pathogenesis of chronic inflammation. Selaginella tamariscina is used as an oriental medicine for its anti-inflammatory effects. Here, we isolated taiwaniaflavone from S. tamariscina and investigated whether taiwaniaflavone affects the induction of iNOS and COX-2 in RAW264.7 macrophages stimulated with lipopolysaccharide. We found that taiwaniaflavone blocks the transactivations of iNOS and COX-2 genes by blocking the nuclear translocation of p65 and subsequent nuclear factor-kappaB inactivation. It is known that NF-kappaB activation is controlled by the phosphorylation and subsequent degradation of I-kappaBalpha, and in the present study, we found that the phosphorylation and degradation of I-kappaBalpha were also inhibited by taiwaniaflavone. Our findings indicate that taiwaniaflavone may provide a developmental basis for an agent against inflammatory diseases.
College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.
Yuba Raj
YR
Pokharel
Jin Won
JW
Yang
Ji Young
JY
Kim
Hyun Woo
HW
Oh
Hye Gwang
HG
Jeong
Eun-Rhan
ER
Woo
Keon Wook
KW
Kang
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004790:Enzyme Induction; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D032503:Selaginellaceae / Q000737:chemistry; D015533:Transcriptional Activation
D052246:Cyclooxygenase 2 Inhibitors; D047309:Flavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C518734:taiwaniaflavone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2