title: Inhibitory effects of EGb761 on the expression of matrix metalloproteinases (MMPs) and cartilage matrix destruction.
abstract: Cytokines such as tumor necrosis factor alpha (TNF-α)-induced expression of matrix metalloproteinase (MMP) play a pivotal role in the destruction of articular cartilage in patients who are suffering from osteoarthritis (OA). Collagen type II, the basis for articular cartilage, can be degraded by MMP-1, MMP-3, and 13. EGb761, the standardized extract of Ginkgo biloba produced by Dr. Willar Schwabe Pharmaceuticals, has shown its anti-inflammatory capacity. This study aimed to determine a mechanism whereby EGb761 may inhibit cartilage degradation. Our results indicated that pretreatment with EGb761 abolishes MMP-1, MMP-3, and MMP-13 gene expression and protein expression induced by TNF-α in human chondrocyte monolayer. In addition, the reduction of the tissue inhibitor of metalloproteinase-1(TIMP-1) and metalloproteinase-2 gene expression induced by TNF-α was rescued by pretreatment with EGb761. Importantly, TNF-α-induced degradation of collagen type II was ameliorated by EGb761 in a dose-dependent manner. Mechanistically, our results indicated that EGb761 treatment attenuated TNF-α-induced NF-κB activation. These actions of EGb761 suggest a mechanism by which EGb761 may act to prevent cartilage breakdown in arthritis.
authors.affiliation: Department of Joint Surgery, Weifang Medical University, Weifang, China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Wang
authors.forename: Xingshen
authors.initials: X
authors.lastname: Zhao
authors.forename: Shusen
authors.initials: S
authors.lastname: Tang
mesh_terms: D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D020441:Ginkgo biloba; D006801:Humans; D064235:Matrilin Proteins / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000096983:Ginkgo Extract
chemical_list: D064235:Matrilin Proteins; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C577539:MATN1 protein, human; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C507079:MMP13 protein, human; C511768:MMP3 protein, human; C522360:MMP1 protein, human