title: The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis.
abstract: BACKGROUND
  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).
  
  
  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).
  
  
  CONCLUSIONS
  This study demonstrated that CK downregulated memory B cells in AA rats, and this down-regulation may be T-cell dependent.
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Huaxun
authors.initials: H
authors.lastname: Wu
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Liu
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: a Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education , Hefei , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant; D036145:Ginsenosides / Q000494:pharmacology*; D007156:Immunologic Memory / Q000187:drug effects*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D023201:CD40 Ligand; D005620:Freund's Adjuvant; D036145:Ginsenosides; C112772:ginsenoside compound K
keywords: Autoimmune; inflammation; triterpene saponins