Compound K, a Metabolite of Ginsenosides, Attenuates Collagen-induced Arthritis in Mice

Abstract

Objective Although several ginsenosides have been reported to have anti-arthritic activity, few in vivo studies of the anti-ar-thritic effects of compound K (CK), a major metabolite of ginsenosides, have been conducted. Therefore, we investigated the preventative and therapeutic effects of CK on collagen-induced arthritis (CIA). Methods CK was administered to CIA mice pre-ventively and therapeutically and post-treatment bone microarchitectural characteristics, histopathological changes, and serum levels of anti-collagen antibodies, tumor necrosis factor-α, and interleukin (IL)-17 were investigated. We also examined cytokine production by type II collagen (CII)-stimulated splenocytes and mRNA expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase (TIMP)-1, receptor activator of nuclear factor-κ B ligand (RANKL), and osteoprotegerin (OPG) in the joint tissues. Results CK reduced the severity of CIA preventively and therapeutically (all p＜0.05). Additionally, CK dose-dependently decreased histopathological signs of arthritis and improved microarchitectural characteristics (all p ＜0.05) at 10 to 20 mg/kg/d in CIA mice. CK treatment significantly decreased the serum levels of anti-CII immunoglobulin G (p＜0.01) and the secretion of interferon-γ and IL-2 from stimulated splenocytes (all p＜0.05). Furthermore, MMP-3/TIMP-1 and RANKL/OPG ratios were suppressed in CK treated mice (all p＜0.01). Conclusion CK attenuated CIA via suppression of the humoral immune response and modulation of joint-destructive mediators. These results suggest that CK has therapeutic potential in rheumatoid arthritis.