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-arthritic 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 preventively 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-κB 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 (J Rheum Dis 2015;22:154-166)

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

“…Notably, a positive correlation (R 2 = 0.9830, p = 0.0009) was found in percentages of activated T-cells and DCs, while a negative correlation (R 2 = 0.8348, p = 0.03) in percentages of naïve T cells and DCs [ 61 ]. In another study, CK suppressed humoral immune response of T helper type 1 (Th1) cells and significantly suppressed expressions of matrix metalloproteinases (MMP)-3 and-13 and receptor activator of NF-κB ligand (RANKL) [ 62 ]. Concerning effects on B cells, CK was described as reducing the percentage of memory B cells.…”

Effect of the Gintonin-Enriched Fraction on Glucagon-Like-Protein-1 Release

“…Similarly, compound K, a ginsenoside metabolite, exhibited in vitro anti-inflammatory effects in a dose-dependent manner by reducing inflammatory cytokines. However, in an in vivo study, oral administration of compound K did not show a dose-dependent effect on arthritis score in mice [43]. Currently, we cannot explain exactly why the low dosage of GEF In addition, ginsenosides, also known as ginseng saponins, reportedly trigger GLP-1 release from NCI-H716 cells [27,42].…”

Ginsenoside Rg3 Alleviates Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4+CD25+Foxp3+Treg Cells

“…GRg3 belongs to the dammarane type and is a degradation product of ginsenoside Rb1, ginsenoside Rb2, and ginsenoside Rc by the biotransformation. , GRg3 also can be biotransformed by intestinal bacteria into ginsenoside Rh2 and 20­( S )-protopanaxadiol [20­( S )-PPD] . Published papers have confirmed the anti-arthritis effects of ginsenosides, including ginsenoside compound K, − ginsenoside Rbl, ginsenoside Rg1, − Rg3-, Rk1-, and Rg5-rich ginsenoside extracts, etc. As shown above, most of the ginsenosides belong to the dammarane type, including ginsenoside compound K, ginsenoside Rb1, and ginsenoside Rg1.…”