Erschienen in:
01.08.2013 | Original Article
Joint-protective effects of compound K, a major ginsenoside metabolite, in rheumatoid arthritis: in vitro evidence
verfasst von:
Yong Seok Choi, Eun Ha Kang, Eun Young Lee, Hyun Sik Gong, Heun Soo Kang, Kichul Shin, Eun Bong Lee, Yeong Wook Song, Yun Jong Lee
Erschienen in:
Rheumatology International
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Ausgabe 8/2013
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Abstract
Regulatory expression of matrix metalloproteinases (MMPs) and osteoclastogenesis is implicated in the process of joint destruction in rheumatoid arthritis (RA). Although several reports suggested the anti-arthritic effects of ginseng saponins, it has not been investigated whether the most absorbable ginsenoside, compound K (CK), has a joint-protective action. We here investigated the effect of CK (0–5 μM) on TNF-α-induced MMP-1, MMP-3, and MMP-13 and TIMP-1 production from RA fibroblast-like synoviocytes (FLS) and determined the inhibitory effect of CK on osteoclastogenesis from RAW264.7 cells co-cultured with RA-FLS and from human CD14+ monocytes. The effect of CK on NF-κB, nuclear factor of activated T cells c1 (NFATc1), and mitogen-activated protein kinases pathways were evaluated using immunoblotting or specific inhibitors. CK significantly inhibited MMP-1 and MMP-3 productions from RA-FLS in a concentration-dependent manner through suppressing the JNK and ERK pathways. In the co-culture system of TNF-α-stimulated RA-FLS and RAW264.7 cells, CK dose-dependently reduced receptor activator of NF-κB ligand (RANKL) expression in the RA-FLS and inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells. Furthermore, CK significantly inhibited soluble RANKL-induced osteoclastogenesis or osteoclast activity in RAW264.7 cells and human CD14+ monocytes through inhibition of RANKL-induced IκBα degradation and NFATc1 expression. In conclusion, our results increase the understanding of the molecular mechanisms of the joint-protective effects of CK in RA. The characteristic actions of CK provide in vitro evidence for its potential utility in RA therapy.