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The therapeutic potential of ginkgolide K in experimental autoimmune encephalomyelitis via peripheral immunomodulation.

Abstract
Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.
AuthorsWen-Bo Yu, Qing Wang, Sheng Chen, Liang Cao, Jie Tang, Cun-Gen Ma, Wei Xiao, Bao-Guo Xiao
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 70 Pg. 284-294 (May 2019) ISSN: 1878-1705 [Electronic] Netherlands
PMID30851709 (Publication Type: Journal Article)
CopyrightCopyright © 2019. Published by Elsevier B.V.
Chemical References
  • Anti-Inflammatory Agents
  • Cytokines
  • Ginkgolides
  • Lactones
  • Platelet Activating Factor
  • ginkgolide K
Topics
  • Animals
  • Anti-Inflammatory Agents (therapeutic use)
  • Cell Differentiation
  • Cells, Cultured
  • Cellular Microenvironment
  • Chemotaxis
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental (diet therapy)
  • Female
  • Ginkgolides (therapeutic use)
  • Humans
  • Lactones (therapeutic use)
  • Mice
  • Mice, Inbred C57BL
  • Microglia (physiology)
  • Multiple Sclerosis (drug therapy)
  • Platelet Activating Factor (antagonists & inhibitors)
  • T-Lymphocytes, Regulatory (immunology)
  • Th1-Th2 Balance (drug effects)
  • Th17 Cells (immunology)

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