Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells

Mol Neurobiol. 2016 Apr;53(3):1977-2002. doi: 10.1007/s12035-015-9131-4. Epub 2015 Apr 7.

Abstract

The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.

Keywords: Experimental autoimmune encephalomyelitis; Ginsenosides; Korean red ginseng; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Chemokines / metabolism
  • Chronic Disease
  • Demyelinating Diseases / complications
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Fibronectins / metabolism
  • Ginsenosides / pharmacology
  • Ginsenosides / therapeutic use*
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice, Inbred C57BL
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Panax / chemistry*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Inbred Lew
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Up-Regulation / drug effects*

Substances

  • Chemokines
  • Fibronectins
  • Ginsenosides
  • Plant Extracts
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • ginsenoside Rb1
  • ginsenoside Rg1