Methanol extracts of Stewartia koreana inhibit cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression by blocking NF-kappaB transactivation in LPS-activated RAW 264.7 cells.
Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and PGE2 production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-kappaB reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-kappaB DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of IkappaB-alpha and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.
Lee
Tae Hoon
TH
Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University, Yongin 446-701, Korea.
Kwak
Han Bok
HB
Kim
Hong-Hee
HH
Lee
Zang Hee
ZH
Chung
Dae Kyun
DK
Baek
Nam-In
NI
Kim
Jiyoung
J
D000818:Animals; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects*; D000432:Methanol / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D028242:Theaceae / Q000737:chemistry*; D015533:Transcriptional Activation / Q000187:drug effects
D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D000432:Methanol