BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin

J Ethnopharmacol. 2012 May 7;141(1):290-300. doi: 10.1016/j.jep.2012.02.034. Epub 2012 Feb 27.

Abstract

Ethnopharmacological relevance: Paeoniflorin (Pae) is extracted from the root of paeonia lactiflora which have attracted attention for anti-rheumatic and immune modulating properties.

Aim of the study: To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen-induced arthritis (CIA).

Materials and methods: CIA rats were randomly separated into different groups and treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt and mTOR.

Results: In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF-R, PI3K, p-Akt and mTOR.

Conclusion: PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats. Pae had therapeutic effects on rats with CIA. These effects might be relative to regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the antibodies production further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle Joint / drug effects
  • Ankle Joint / enzymology
  • Ankle Joint / immunology
  • Ankle Joint / pathology
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / enzymology
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Autoantibodies / blood*
  • B-Cell Activating Factor / immunology*
  • B-Cell Activation Factor Receptor / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • Benzoates / isolation & purification
  • Benzoates / pharmacology*
  • Bridged-Ring Compounds / isolation & purification
  • Bridged-Ring Compounds / pharmacology*
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Male
  • Monoterpenes
  • Paeonia* / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Phytotherapy
  • Plant Roots
  • Plants, Medicinal
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Spleen / drug effects
  • Spleen / enzymology
  • Spleen / immunology
  • Spleen / pathology
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Autoantibodies
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Benzoates
  • Bridged-Ring Compounds
  • Glucosides
  • Monoterpenes
  • peoniflorin
  • mTOR protein, rat
  • Pik3cd protein, rat
  • Akt1 protein, rat
  • Akt2 protein, rat
  • Akt3 protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases