TY - JOUR
T1 - Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells
AU - Lee, Min Jung
AU - Jang, Minhee
AU - Choi, Jonghee
AU - Chang, Byung Soo
AU - Kim, Do Young
AU - Kim, Sung Hoon
AU - Kwak, Yi Seong
AU - Oh, Seikwan
AU - Lee, Jong Hwan
AU - Chang, Byung Joon
AU - Nah, Seung Yeol
AU - Cho, Ik Hyun
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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 glycoprotein35–55-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.
AB - 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 glycoprotein35–55-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.
KW - Experimental autoimmune encephalomyelitis
KW - Ginsenosides
KW - Korean red ginseng
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=84961119667&partnerID=8YFLogxK
U2 - 10.1007/s12035-015-9131-4
DO - 10.1007/s12035-015-9131-4
M3 - Article
C2 - 25846819
AN - SCOPUS:84961119667
SN - 0893-7648
VL - 53
SP - 1977
EP - 2002
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 3
ER -