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

Pharm Biol. 2016 Jul;54(7):1280-8. doi: 10.3109/13880209.2015.1074254. Epub 2016 May 24.

Abstract

Context: Compound K (CK, 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, is structurally a member of the dammarane-type triterpene saponins. Several studies have identified the anti-inflammatory activity of CK. Our previous study demonstrated that CK exerted its anti-inflammatory effect via inhibition of abnormal activation and differentiation of T cells. However, its mechanism of action on B cells remains unclear.

Objective: The objective of this study is to investigate the effect and underlying mechanisms of CK's effects on memory B cells in the setting of adjuvant-arthritis (AA).

Materials and methods: Complete Freund's adjuvant was used to induce AA in rats. Rats were administered, either CK (10, 40, and 160 mg/kg), once daily for 15 d, or methotrexate (MTX; 0.5 mg/kg) once every 3 d, for a total of six times. To evaluate the anti-inflammatory effect of CK, a global assessment and a swollen joint count of AA rats were performed every 3 d. Spleen index and histopathology were examined. Subsets of B cells including CD45R(+)IgM(+) (total B cells) and CD45R(+)CD27(+) (memory B cells) and expression of CD40 and CD40L were assayed by flow cytometry.

Results: Compared with the AA rats, global assessment scores and swollen joint counts were significantly lower in the treated groups received CK (40 and 160 mg/kg; p < 0.05 and p < 0.01, respectively). CK (40 and 160 mg/kg) decreased the spleen index (p < 0.01), and alleviated hyperplasia of lymph nodes (p < 0.05 and p < 0.01, respectively) and marginal zone (p < 0.05) in the spleen. In addition, CK (40 and 160 mg/kg) suppressed memory B cell subsets (p < 0.05), and suppressed CD40L expression on T cells and CD40 expression on B cells (p < 0.05 and p < 0.01, respectively).

Discussion and conclusion: This study demonstrated that CK downregulated memory B cells in AA rats, and this down-regulation may be T-cell dependent.

Keywords: Autoimmune; inflammation; triterpene saponins.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Dose-Response Relationship, Drug
  • Freund's Adjuvant*
  • Ginsenosides / pharmacology*
  • Immunologic Memory / drug effects*
  • Joints / drug effects
  • Joints / pathology
  • Male
  • Phenotype
  • Rats, Sprague-Dawley
  • Spleen / drug effects*
  • Spleen / immunology
  • Spleen / metabolism
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • CD40 Antigens
  • Ginsenosides
  • CD40 Ligand
  • Freund's Adjuvant
  • ginsenoside M1