title: An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.
abstract: The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Brain Korea 21 Plus Program, 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 Convergence Medical Science, 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 Science, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Acupuncture & Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
authors.affiliation: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, 336-745, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Integrative Plant Science, Chung-Ang University, Anseong, 456-756, Republic of Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Medicinal Crop Research Institute, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea.
authors.forename: Young Ock
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Brain Korea 21 Plus Program, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea; Institute of Koreran Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008518:Medicine, East Asian Traditional / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010243:Paralysis / Q000188:drug therapy* / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D063308:Myelin-Oligodendrocyte Glycoprotein