Ginkgo biloba Extract Individually Inhibits JNK Activation and Induces c-Jun Degradation in Human Chondrocytes: Potential Therapeutics for OsteoarthritisReport as inadecuate




Ginkgo biloba Extract Individually Inhibits JNK Activation and Induces c-Jun Degradation in Human Chondrocytes: Potential Therapeutics for Osteoarthritis - Download this document for free, or read online. Document in PDF available to download.

Osteoarthritis OA is a common joint disorder with varying degrees of inflammation. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. We examined the anti-inflammatory effects of Ginkgo biloba extract EGb in interleukin-1 IL-1-stimulated human chondrocytes. Chondrocytes were prepared from cartilage specimens taken from patients with osteoarthritis who had received total hip or total knee replacement. The concentrations of chemokines and the degree of cell migration were determined by ELISA and chemotaxis assays, respectively. The activation of inducible nitric oxide synthase iNOS, mitogen-activated protein kinases MAPKs, activator protein-1 AP-1, and nuclear factor-kappaB NF-κB was determined by immunoblotting, immunohistochemistry, and electrophoretic mobility shift assay. We found that EGb inhibited IL-1-induced production of chemokines, which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and release of nitric oxide NO. The EGb-mediated suppression of the iNOS-NO pathway correlated with the attenuation of activator protein-1 AP-1 but not nuclear factor-kappaB NF-κB DNA-binding activity. Of the mitogen-activated protein kinases MAPKs, EGb inhibited only c-Jun N-terminal kinase JNK. Unexpectedly, EGb selectively caused degradation of c-Jun protein. Further investigation revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c-Jun and could be prevented by the proteosome inhibitor MG-132. The results imply that EGb protects against chondrocyte degeneration by inhibiting JNK activation and inducing ubiquitination-dependent c-Jun degradation. Although additional research is needed, our results suggest that EGb is a potential therapeutic agent for the treatment of OA.



Author: Ling-Jun Ho, Li-Feng Hung, Feng-Cheng Liu, Tsung-Yun Hou, Leou-Chyr Lin, Chuan-Yueh Huang, Jenn-Haung Lai

Source: http://plos.srce.hr/



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