title: EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee.
abstract: Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti-inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)- and IL-1β-induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX-2 and iNOS in human chondrocytes. LPS was also seen to up-regulate the expressions of toll-like receptor-4 (TLR4), its downstream signal TNF receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB signaling. These LPS-induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL-1β as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX-2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti-inflammatory effects on human articular chondrocytes and OA rats.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ying Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Keh Sung
authors.initials: KS
authors.lastname: Tsai
authors.forename: Chen Yuan
authors.initials: CY
authors.lastname: Chiu
authors.forename: Ting Hua
authors.initials: TH
authors.lastname: Yang
authors.forename: Tzu Hung
authors.initials: TH
authors.lastname: Lin
authors.forename: Wen Mei
authors.initials: WM
authors.lastname: Fu
authors.forename: Cheng Feng
authors.initials: CF
authors.lastname: Chen
authors.forename: Rong Sen
authors.initials: RS
authors.lastname: Yang
authors.forename: Shing Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D020441:Ginkgo biloba; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D051546:Cyclooxygenase 2; D015232:Dinoprostone; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; D014443:Tyrosine; C495345:TLR4 protein, human; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C002744:3-nitrotyrosine; C496540:PTGS2 protein, human