title: Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.
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.
authors.affiliation: Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Department of Convergence Medical Sciences, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Department of Convergence Medical Sciences, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Minhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Convergence Medical Sciences, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.|Brain Korea 21 Plus Program, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jonghee
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Cosmetology, Hanseo University, Seosan, 356-706, Republic of Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Chang
authors.affiliation: Barrow Neurological Institute and St. Joseph's Medical Center, Phoenix, AZ, 85013, USA.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Central Research Institute, Korea Ginseng Corporation, Daejeon, 305-805, Republic of Korea.
authors.forename: Yi-Seong
authors.initials: YS
authors.lastname: Kwak
authors.affiliation: Department of Neuroscience and Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, 158-710, Republic of Korea.
authors.forename: Seikwan
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Chang
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Convergence Medical Sciences, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.|Institute of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.|Brain Korea 21 Plus Program, Kyung Hee University, Seoul, 130-701, Republic of Korea. ihcho@khu.ac.kr.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018925:Chemokines; D005353:Fibronectins; D036145:Ginsenosides; D010936:Plant Extracts; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C442759:ginsenoside Rb1; C035054:ginsenoside Rg1
keywords: Experimental autoimmune encephalomyelitis; Ginsenosides; Korean red ginseng; T cell
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