Ginsenoside Metabolite Compound K Alleviates Adjuvant-Induced Arthritis by Suppressing T Cell Activation

Abstract

Ginsenoside metabolite compound K (CK) is the degradation product of ginsenosides in the intestine by bacteria and has many pharmacological activities including anti-inflammatory effects. Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease characterized by chronic synovial inflammation and articular damage in multiple joints. However, the effect of CK on RA remains unclear. In this study, the effect of CK on adjuvant arthritis (AA) and the underlying mechanisms that focused on T cell activation were investigated. Complete Freund's adjuvant was used to induce AA rats. After the onset of arthritis, rats were given CK (10, 40, and 160 mg/kg) or MTX (0.5 mg/kg). To evaluate the severity of arthritis, arthritis index and paw swelling were evaluated every 3 days. Histopathology of joint and spleen were assayed. Subsets of T cells including CD4+CD62L+ (naïve T cells), CD4+CD25+ (activated T cells), and CD4+CD25 + Foxp3+ cells (Treg) and CD25 expression were assayed by flow cytometry. Proliferation of T cell was evaluated by (3)H-TdR. IL-2 level was assayed by ELISA. We found that CK attenuated arthritis index and paw swelling, restored the histopathological change of joint and spleen, downregulated the percentage of activated T cells, and upregulated naïve T cells and Treg cells in spleen. CK significantly suppressed T cell activation (as indicated by T cell proliferation, CD25 expression, and IL-2 production). In conclusion, our results suggest that CK alleviates autoimmune arthritis by suppressing T cell activation.

The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis

“…The CD40L/CD40 signaling pathway is critically involved in the differentiation of B cells. CD40 is a 50-kDa trans-membrane glycoprotein and is expressed in B cells; its ligand, CD40L, also named We also found that CK suppressed the activation of T cells as well as production of IL-2 in AA rats (Chen et al, 2014). These results suggest that the inhibitory effect of CK on memory B cells may be T cell-dependent.…”

“…Pharmacol Res 68:38-45. Wu H, Chen J, Wang Q, et al (2014). Ginsenoside metabolite compound K attenuates inflammatory responses of adjuvant-induced arthritis rats.…”

“…Rats are immunized with heat-killed Bacillus Calmette Guerin (BCG) in liquid paraffin and subsequently develop adjuvant-induced arthritis (AA) through a mechanism involving heat shock proteins. Therefore, AA is the most widely used model for studies of RA pathogenesis, and for the screening of new drugs for the treatment of RA (Chang et al, 2011;Chen et al, 2014;Song et al, 2013;Wu et al, 2014). Motivated by the aforementioned findings, the present study assessed the effects of CK on memory B cells in AA rats.…”

“…CK also exerts anti-inflammatory effects by inhibiting cyclooxygenase-2 expression (Park et al, 2005). Our previous work demonstrated that CK attenuated arthritis in animal models by suppressing T cell activation, inhibiting the production of inflammatory cytokines such as IL-1b, tumor necrosis factor-alpha (TNF-a), IL-2, and IL-17, inhibiting the proliferation of B cells, and decreasing autoantibody levels (Chen et al, 2014;Liu et al, 2014;Wu et al, 2014). However, its effect and mechanism of action on memory B cells remains unclear.…”

Ginsenoside metabolite compound K exerts anti-inflammatory effect via suppressing T cell activation

“…Our previous studies showed that CK attenuated adjuvant-induced arthritis (AA) and collagen-induced arthritis (CIA) by suppressing T cell activation [10][11][12] . Our understanding of the immunopathology of autoimmune disease has been improved by recent progress in the research of T cells.…”