Matrine suppresses expression of adhesion molecules and chemokines as a mechanism underlying its therapeutic effect in CNS autoimmunity

Immunol Res. 2013 May;56(1):189-96. doi: 10.1007/s12026-013-8393-z.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a classical experimental model of multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Previous reports have suggested that matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, could inhibit clinical EAE, but its mechanism of action is not clear. Our present study showed that MAT treatment resulted in dose-dependent reduction in neurological scores. Consistent with this observation, infiltration of inflammatory cells and demyelination in the CNS were also significantly suppressed. We further studied the mechanism underlying these effects of MAT by determining whether this treatment influences expression of molecules that are involved in the activation and migration of inflammatory cells. Our results showed that MAT significantly inhibited expression and production in the CNS of ICAM-1 and VCAM-1, key adhesive molecules, and CCL3 and CCL5, key chemokines, that attract inflammatory cells into the CNS. Furthermore, the TLR4/MD2 pathway, which plays an important role in the induction of Th1/Th17 cells in EAE, was also significantly inhibited. Together, our study not only demonstrates that MAT may be a novel therapeutic option for the treatment for MS, but also provides further information on mechanisms underlying the effect of MAT treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitum / immunology
  • Alkaloids / administration & dosage*
  • Animals
  • Autoimmunity / drug effects
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Central Nervous System / drug effects
  • Chemokine CCL3 / metabolism
  • Chemokine CCL5 / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Quinolizines / administration & dosage*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Alkaloids
  • Chemokine CCL3
  • Chemokine CCL5
  • Quinolizines
  • Toll-Like Receptor 4
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • matrine