Ginsenoside Metabolite Compound K Suppresses T-Cell Priming via Modulation of Dendritic Cell Trafficking and Costimulatory Signals, Resulting in Alleviation of Collagen-Induced Arthritis

Abstract

Ginsenoside metabolite compound K (CK; 20-O-D-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, belongs to the dammarane-type triterpene saponins, according to its structure. The anti-inflammatory activity of CK has been identified in several studies. Our study demonstrated that CK exerted an anti-inflammatory effect in collagen-induced arthritis (CIA) and adjuvant-induced arthritis animal models, and this effect was due to inhibition of the abnormal activation and differentiation of T cells. However, the mechanism of CK in suppressing T-cell activation remains unclear. In this study, CK had a therapeutic effect in mice with CIA, decreased the percentage of activated T cells and dendritic cells (DCs), and increased the percentage of naive T cells in lymph nodes. The inhibitory effect on T-cell activation of CK was related to suppression of accumulation of DCs in lymph nodes. CK decreased CCL21 levels in lymph nodes and CCR7 expression in DCs and suppressed CCL21/CCR7-mediated migration of DCs, thus reducing accumulation of DCs in lymph nodes. In addition, signals for T-cell activation including major histocompatibility complex class II and costimulatory molecules, such as CD80 and CD86, were suppressed by CK, and the proliferation of T cells induced by DCs was inhibited by CK. In conclusion, this study demonstrated that CK downregulated DC priming of T-cell activation in CIA, and suppression of CCL21/CCR7-mediated DC migration and signaling between T cells and DCs might be the potential mechanism. These results provide an interesting, novel insight into the potential mechanism by which CK contributes to the anti-inflammatory effect in autoimmune conditions.

Ginsenoside metabolite compound K exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and Tumor necrosis factor receptor type 2

“…In addition, CK decreased the percentage of activated T-cell subsets such as CD4 þ CD154 þ T and CD4 þ CD69 þ T, and increased the percentage of naive T-cells (CD4 þCD62Lþ ) of spleen . CK relieved the excessive T cells activation by suppressing signals provided by CD80/CD86-CD28, MHCII-TCR and CD25-IL-2 (Chen et al, 2015). And these studies also demonstrated that CK exerted anti-arthritis effect in AA and CIA.…”

“…CK possesses several pharmacological activities including antitumor, anti-inflammatory and anti-allergic action (Helliwell et al, 2015;Radad et al, 2011). Our previous studies demonstrated that CK played their anti-inflammatory and immunoregulatory effect in collagen-induced arthritis (CIA) and adjuvant arthritis (AA) by inhibiting abnormal T cells activation and differentiation (Chen et al, , 2015Wu et al, 2014;Liu et al, 2014). CK suppressed T cells proliferation in vivo and in vitro.…”

Promotion of compound K production in Saccharomyces cerevisiae by glycerol

“…Ginsenoside compound K (CK), the primary deglycosyl metabolite of ginsenosides produced under the action of intestinal flora and absorbed into the body, has been proven to elicit anticancer, anti-inflammatory, anti-allergic, antidiabetic, anti-angiogenic, anti-aging, neuroprotective, and liver protective properties among several notable biological characteristics [2]. Ginsenoside CK is a rare ginsenoside derived from ginseng saponins Rb1 and Rb2 by intestinal bacteria [3]. The method of synthesis of CK has garnered significant attention.…”

Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng

“…Ginsenoside compound K (CK), or 20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol (The molecular structure is shown in Fig 1 ), is naturally absent. It belongs to the rare ginsenoside, which is transformed from ginsenosideRb1 and Rb2 by intestinal bacteria [ 5 ]. Ginsenosides are poorly absorbed from the gut while their metabolite CK is absorbed.…”