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KMID : 1084220180250030188
Journal of Rheumatic Diseases
2018 Volume.25 No. 3 p.188 ~ p.196
Compound K Inhibits Interleukin-1¥â-induced Expression of Inflammatory Mediators and Matrix Metalloproteinases by Inhibiting Mitogen-activated Protein Kinase Activation in Chondrocytes
Park Eun-Hye

Kim Ji-Soo
Lee Jeong-Seok
Lee Yun-Jong
Song Yeong-Wook
Lee Eun-Young
Abstract
Objective. This study examined the anti-inflammatory and chondroprotective effects of compound K (CK), a ginsenoside metabolite, on chondrocytes from osteoarthritis (OA) patients following stimulation with interleukin (IL)-1¥â.

Methods: Articular cartilage samples were obtained from six OA patients undergoing total knee replacement surgery. Nitric oxide (NO) production was measured by the Griess reaction. Subsequently, the mRNA and protein levels of matrix metalloproteinases (MMPs), inducible NO synthase (iNOS), and mitogen-activated protein kinases (MAPKs) were examined by a reverse transcription-polymerase chain reaction and western blot analysis. Cartilage degradation was assessed using a glycosaminoglycan (GAG) assay.

Results: CK inhibited IL-1¥â-induced NO production and iNOS expression in a dose-dependent manner. In addition, it inhibited the IL-1¥â-stimulated release of MMP-1, -3, and -13 and tissue inhibitor of matrix metalloproteinase-1 from OA patient chondrocytes. In addition, CK effectively suppressed the IL-1¥â-induced phosphorylation of p38, extracellular signal-regulated kinase-1/2, and c-Jun N-terminal kinase MAPKs. Moreover, the IL-1¥â-mediated release of GAG was inhibited by CK in a dose-dependent manner.

Conclusion: CK inhibited the IL-1¥â-induced expression of inflammatory mediators and MMPs by, at least in part, inhibiting MAPK activation, and has potential as a therapeutic agent for the treatment of OA.
KEYWORD
Panax, Ginsenosides, Nitric oxide, Matrix metalloproteinases, Osteoarthritis
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