Joint-protective effects of compound K, a major ginsenoside metabolite, in rheumatoid arthritis: in vitro evidence.
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.
Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Korea.
Yong Seok
YS
Choi
Eun Ha
EH
Kang
Eun Young
EY
Lee
Hyun Sik
HS
Gong
Heun Soo
HS
Kang
Kichul
K
Shin
Eun Bong
EB
Lee
Yeong Wook
YW
Song
Yun Jong
YJ
Lee
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D036145:Ginsenosides; D020782:Matrix Metalloproteinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C112772:ginsenoside compound K