EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee

J Orthop Res. 2013 Jul;31(7):1032-8. doi: 10.1002/jor.22339. Epub 2013 Mar 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism*
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Ginkgo biloba
  • Humans
  • Interleukin-1beta / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / prevention & control*
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Wistar
  • Toll-Like Receptor 4 / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Ginkgo biloba extract
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone