title: Preventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via suppression of nuclear factor-kappaB in RAW 264.7 cells.
abstract: During our ongoing efforts to identify bioactive natural products with anti-inflammatory activity, we produced an extract from Ginkgo biloba (GBB) which contains higher levels of the active principles terpene and biflavonoid than EGb, the standard commercially available extract. In the present study, we examined and compared the effects of these two extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Our data indicate that GBB is a more potent inhibitor of NO and PGE2 production than EGb 761, and it also significantly decreased tumor necrosis factor (TNF)-alpha release. Consistent with these observations, the protein and mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be inhibited by GBB in a dose-dependent manner. Furthermore, GBB inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), which was associated with the prevention of IkappaB degradation, and subsequently with decreased p65 protein level in the nucleus. These results suggest that GBB inhibits LPS-induced iNOS, COX-2 and TNF-alpha expressions through the down-regulation of NF-kappaB-DNA binding activity.
authors.affiliation: Department of Biochemistry, College of Pharmacy, Kyung-Hee University, Seoul, South Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Park
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Won
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Yun
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Yong-Nam
authors.initials: YN
authors.lastname: Han
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Choi
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D020441:Ginkgo biloba / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D012313:RNA; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C022616:thiazolyl blue