Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice

Eur J Pharmacol. 2006 Feb 15;531(1-3):270-9. doi: 10.1016/j.ejphar.2005.11.062. Epub 2006 Jan 17.

Abstract

T cell immune responses play important roles in the pathogenesis of systemic lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo nucifera suppresses T cells proliferation. To study its potential benefit on SLE, we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)-armepavine for 6 weeks and their SLE characteristics were evaluated. The results revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin-10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular hypercellularity and immune complexes deposition, and decrease of urinary protein and anti-double stranded DNA autoantibody production. Furthermore, the data demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Antibodies, Antinuclear / blood
  • Benzylisoquinolines / isolation & purification
  • Benzylisoquinolines / pharmacology
  • Benzylisoquinolines / therapeutic use*
  • Cell Proliferation / drug effects
  • Cytokines / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression / drug effects
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-2 / blood
  • Interleukin-2 / genetics
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / mortality
  • Lymphatic Diseases / prevention & control
  • Mice
  • Mice, Inbred MRL lpr
  • Nelumbo / chemistry*
  • Phytohemagglutinins / pharmacology
  • Phytotherapy
  • Proteinuria / prevention & control
  • Proteinuria / urine
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seeds / chemistry
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • Survival Rate

Substances

  • Alkaloids
  • Antibodies, Antinuclear
  • Benzylisoquinolines
  • Cytokines
  • Interleukin-2
  • Phytohemagglutinins
  • RNA, Messenger
  • Interferon-gamma
  • armepavine