用户名: 密码: 验证码:
Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells
详细信息    查看全文
  • 作者:Min Jung Lee ; Minhee Jang ; Jonghee Choi ; Byung Soo Chang…
  • 关键词:Korean red ginseng ; Ginsenosides ; Experimental autoimmune encephalomyelitis ; T cell
  • 刊名:Molecular Neurobiology
  • 出版年:2016
  • 出版时间:April 2016
  • 年:2016
  • 卷:53
  • 期:3
  • 页码:1977-2002
  • 全文大小:3,003 KB
  • 参考文献:1.Lassmann H, van Horssen J (2011) The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett 585:3715–3723CrossRef PubMed
    2.McFarland HF, Martin R (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8:913–919CrossRef PubMed
    3.Ragheb S, Lisak R (1993) Multiple sclerosis: genetic background versus environment. Ann Neurol 34:509–510CrossRef PubMed
    4.Serafini B, Rosicarelli B, Franciotta D, Magliozzi R, Reynolds R, Cinque P, Andreoni L, Trivedi P et al (2007) Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 204:2899–2912CrossRef PubMed PubMedCentral
    5.Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol 33:579–589CrossRef PubMed
    6.Chen SJ, Wang YL, Fan HC, Lo WT, Wang CC, Sytwu HK (2012) Current status of the immunomodulation and immunomediated therapeutic strategies for multiple sclerosis. Clin Dev Immunol 2012:970789PubMed PubMedCentral
    7.Cuzzola VF, Palella E, Celi D, Barresi M, Giacoppo S, Bramanti P, Marino S (2012) Pharmacogenomic update on multiple sclerosis: a focus on actual and new therapeutic strategies. Pharmacogenomics J 12:453–461CrossRef
    8.Neilley LK, Goodin DS, Goodkin DE, Hauser SL (1996) Side effect profile of interferon beta-1b in MS: results of an open label trial. Neurology 46:552–554CrossRef PubMed
    9.Gasperini C, Ruggieri S (2009) New oral drugs for multiple sclerosis. Neurol Sci 30(Suppl 2):S179–S183CrossRef PubMed
    10.Minagar A (2013) Current and future therapies for multiple sclerosis. Scientifica 2013:249101CrossRef PubMed PubMedCentral
    11.Cho I (2012) Effects of Panax ginseng in neurodegenerative diseases. J Ginseng Res 36:342–353CrossRef PubMed PubMedCentral
    12.Shibata S, Fujita M, Itokawa H, Tanaka O, Ishii T (1963) Studies on the constituents of Japanese and Chinese crude drugs. XI. Panaxadiol, a sapogenin of ginseng roots. Chem Pharm Bull (Tokyo) 11:759–761CrossRef
    13.Kaneko H, Nakanishi K (2004) Proof of the mysterious efficacy of ginseng: basic and clinical trials: clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci 95:158–162CrossRef PubMed
    14.Karmazyn M, Moey M, Gan XT (2011) Therapeutic potential of ginseng in the management of cardiovascular disorders. Drugs
    15.Kim HJ, Kim P, Shin CY (2013) A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J Ginseng Res 37(1):8–29
    16.Lee MS, Yang EJ, Kim JI, Ernst E (2009) Ginseng for cognitive function in Alzheimer’s disease: a systematic review. J Alzheimers Dis 18:339–344PubMed
    17.Van Kampen J, Robertson H, Hagg T, Drobitch R (2003) Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson’s disease. Exp Neurol 184:521–529CrossRef PubMed
    18.Jang M, Lee MJ, Kim CS, Cho IH (2013) Korean Red Ginseng Extract attenuates 3-nitropropionic acid-induced Huntington’s-like symptoms. Evid Based Complement Alternat Med 2013:237207PubMed PubMedCentral
    19.Hwang I, Ahn G, Park E, Ha D, Song JY, Jee Y (2011) An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Immunol Lett 138:169–178CrossRef PubMed
    20.Hwang I, Ha D, Ahn G, Park E, Joo H, Jee Y (2011) Experimental autoimmune encephalomyelitis: association with mutual regulation of RelA (p65)/NF-kappaB and phospho-IkappaB in the CNS. Biochem Biophys Res Commun 411:464–470CrossRef PubMed
    21.Steinman L, Zamvil SS (2006) How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Ann Neurol 60:12–21CrossRef PubMed
    22.Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB et al (2012) A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490:187–191CrossRef PubMed PubMedCentral
    23.Administration, K.F.a.D. (2007) Korea Food and Drug Administration. Korea Food Code. Mun-young Publishing Co., Seoul
    24.Lee MJ, Jang M, Jung HS, Kim SH, Cho IH (2012) Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting neuronal ERK phosphorylation. Mol Pain 8:40CrossRef PubMed PubMedCentral
    25.Oyagi A, Ogawa K, Kakino M, Hara H (2010) Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice. BMC Complement Altern Med 10:45CrossRef PubMed PubMedCentral
    26.Lee MJ, Jang M, Choi J, Lee G, Min HJ, Chung WS, Kim JI, Jee Y, Chae Y, Kim SH, Lee SJ, Cho IH (2015) Bee venom acupuncture alleviates experimental autoimmune encephalomyelitis by upregulating regulatory T cells and suppressing Th1 and Th17 responses. Mol Neurobiol
    27.Jang M, Lee MJ, Cho IH (2014) Ethyl pyruvate ameliorates 3-nitropropionic acid-induced striatal toxicity through anti-neuronal cell death and anti-inflammatory mechanisms. Brain Behav Immun 38:151–165CrossRef PubMed
    28.Fissolo N, Costa C, Nurtdinov RN, Bustamante MF, Llombart V, Mansilla MJ, Espejo C, Montalban X et al (2012) Treatment with MOG-DNA vaccines induces CD4 + CD25 + FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis. J Neuroinflammation 9:139CrossRef PubMed PubMedCentral
    29.Piao ZG, Cho IH, Park CK, Hong JP, Choi SY, Lee SJ, Lee S, Park K et al (2006) Activation of glia and microglial p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury. Pain 121:219–231CrossRef PubMed
    30.VanGuilder HD, Bixler GV, Brucklacher RM, Farley JA, Yan H, Warrington JP, Sonntag WE, Freeman WM (2011) Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment. J Neuroinflammation 8:138CrossRef PubMed PubMedCentral
    31.Cho IH, Hong J, Suh EC, Kim JH, Lee H, Lee JE, Lee S, Kim CH et al (2008) Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death. Brain 131:3019–3033CrossRef PubMed PubMedCentral
    32.Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408CrossRef PubMed
    33.Hong J, Cho IH, Kwak KI, Suh EC, Seo J, Min HJ, Choi SY, Kim CH et al (2011) Microglial Toll-like receptor 2 contributes to kainic acid-induced glial activation and hippocampal neuronal cell death. J Biol Chem 285:39447–39457CrossRef
    34.Fujita H, Nograles KE, Kikuchi T, Gonzalez J, Carucci JA, Krueger JG (2009) Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. Proc Natl Acad Sci U S A 106:21795–21800CrossRef PubMed PubMedCentral
    35.Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V (1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A 88:7438–7442CrossRef PubMed PubMedCentral
    36.Zhu D, Liu M, Yang Y, Ma L, Jiang Y, Zhou L, Huang Q, Pi R et al (2014) Ginsenoside Rd ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice. J Neurosci Res 92:1217–1226CrossRef PubMed
    37.Lobsiger CS, Cleveland DW (2007) Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat Neurosci 10:1355–1360CrossRef PubMed PubMedCentral
    38.Kim JH, Kim S, Yoon IS, Lee JH, Jang BJ, Jeong SM, Lee JH, Lee BH et al (2005) Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacology 48:743–756CrossRef PubMed
    39.Willis CL (2010) Glia-induced reversible disruption of blood–brain barrier integrity and neuropathological response of the neurovascular unit. Toxicol Pathol 39:172–185CrossRef PubMed
    40.Hohlfeld R (1997) Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. Brain 120(Pt 5):865–916CrossRef PubMed
    41.El-behi M, Rostami A, Ciric B (2010) Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol 5:189–197CrossRef PubMed PubMedCentral
    42.Read S, Malmstrom V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192:295–302CrossRef PubMed PubMedCentral
    43.Kennedy KJ, Strieter RM, Kunkel SL, Lukacs NW, Karpus WJ (1998) Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1. J Neuroimmunol 92:98–108CrossRef PubMed
    44.Park JS, Park EM, Kim DH, Jung K, Jung JS, Lee EJ, Hyun JW, Kang JL et al (2009) Anti-inflammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol 209:40–49CrossRef PubMed
    45.Shin T, Ahn M, Matsumoto Y (2012) Mechanism of experimental autoimmune encephalomyelitis in Lewis rats: recent insights from macrophages. Anatomy Cell Biol 45:141–148CrossRef
    46.Bowie LE, Roscoe WA, Lui EM, Smith R, Karlik SJ (2012) Effects of an aqueous extract of North American ginseng on MOG(35–55)-induced EAE in mice. Can J Physiol Pharmacol 90:933–939CrossRef PubMed
    47.Attele AS, Wu JA, Yuan CS (1999) Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 58:1685–1693CrossRef PubMed
    48.Yuan CS, Wang CZ, Wicks SM, Qi LW (2010) Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 34:160–167CrossRef PubMed PubMedCentral
    49.Kim DH (2012) Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 36:1–15CrossRef PubMed PubMedCentral
    50.Kemper KJ (2007) The yin and yang of integrative clinical care, education, and research. Explore (New York, NY) 3:37–41CrossRef
    51.Dan B, Steven C, Erich S, Andrew G (2004) Chinese herbal medicine. Mater Med
    52.Chen X, Ma X, Jiang Y, Pi R, Liu Y, Ma L (2011) The prospects of minocycline in multiple sclerosis. J Neuroimmunol 235:1–8CrossRef PubMed
    53.Guo X, Nakamura K, Kohyama K, Harada C, Behanna HA, Watterson DM, Matsumoto Y, Harada T (2007) Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis. Neurosci Res 59:457–466CrossRef PubMed
    54.Starossom SC, Mascanfroni ID, Imitola J, Cao L, Raddassi K, Hernandez SF, Bassil R, Croci DO et al (2012) Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity 37:249–263CrossRef PubMed PubMedCentral
    55.Fabis MJ, Scott GS, Kean RB, Koprowski H, Hooper DC (2007) Loss of blood–brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models. Proc Natl Acad Sci U S A 104:5656–5661CrossRef PubMed PubMedCentral
    56.Zeng Y, Gu B, Ji X, Ding X, Song C, Wu F (2007) Sinomenine, an antirheumatic alkaloid, ameliorates clinical signs of disease in the Lewis rat model of acute experimental autoimmune encephalomyelitis. Biol Pharm Bull 30:1438–1444CrossRef PubMed
    57.Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med 17:64–70CrossRef PubMed PubMedCentral
    58.Ransohoff RM, Kivisakk P, Kidd G (2003) Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 3:569–581CrossRef PubMed
    59.Steiner O, Coisne C, Cecchelli R, Boscacci R, Deutsch U, Engelhardt B, Lyck R (2010) Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood–brain barrier endothelium. J Immunol 185:4846–4855CrossRef PubMed
    60.Chaudhary P, Marracci GH, Bourdette DN (2006) Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis. J Neuroimmunol 175:87–96CrossRef PubMed
    61.Kan QC, Zhu L, Liu N, Zhang GX (2013) Matrine suppresses expression of adhesion molecules and chemokines as a mechanism underlying its therapeutic effect in CNS autoimmunity. Immunol Res 56:189–196CrossRef PubMed
    62.Ortiz GG, Pacheco-Moises FP, Macias-Islas MA, Flores-Alvarado LJ, Mireles-Ramirez MA, Gonzalez-Renovato ED, Hernandez-Navarro VE, Sanchez-Lopez AL et al (2014) Role of the blood–brain barrier in multiple sclerosis. Arch Med Res 45:687–697CrossRef PubMed
    63.Flynn KM, Michaud M, Madri JA (2013) CD44 deficiency contributes to enhanced experimental autoimmune encephalomyelitis: a role in immune cells and vascular cells of the blood–brain barrier. Am J Pathol 182:1322–1336CrossRef PubMed PubMedCentral
    64.Kim H, Ahn M, Choi S, Kim M, Sim KB, Kim J, Moon C, Shin T (2013) Potential role of fibronectin in microglia/macrophage activation following cryoinjury in the rat brain: an immunohistochemical study. Brain Res 1502:11–19CrossRef PubMed
    65.Muzio L, Cavasinni F, Marinaro C, Bergamaschi A, Bergami A, Porcheri C, Cerri F, Dina G et al (2010) Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis. Mol Cell Neurosci 43:268–280CrossRef PubMed
    66.Wolburg-Buchholz K, Mack AF, Steiner E, Pfeiffer F, Engelhardt B, Wolburg H (2009) Loss of astrocyte polarity marks blood–brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118:219–233CrossRef PubMed
    67.Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517CrossRef PubMed
    68.Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW et al (2004) Myelin proteolipid protein-specific CD4 + CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 101:15434–15439CrossRef PubMed PubMedCentral
    69.Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4 + CD25+ regulatory T cells. Nat Immunol 4:330–336CrossRef PubMed
    70.Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OM (2006) Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 36:2139–2149CrossRef PubMed
    71.Liu YM, Liu XJ, Bai SS, Mu LL, Kong QF, Sun B, Wang DD, Wang JH et al (2010) The effect of electroacupuncture on T cell responses in rats with experimental autoimmune encephalitis. J Neuroimmunol 220:25–33CrossRef PubMed
    72.Le Y, Zhou Y, Iribarren P, Wang J (2004) Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. Cell Mol Immunol 1:95–104PubMed
    73.Szczucinski A, Losy J (2007) Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies. Acta Neurol Scand 115:137–146CrossRef PubMed
    74.Giraud SN, Caron CM, Pham-Dinh D, Kitabgi P, Nicot AB (2010) Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression in reactive astrocytes. Proc Natl Acad Sci U S A 107:8416–8421CrossRef PubMed PubMedCentral
    75.Singh NP, Hegde VL, Hofseth LJ, Nagarkatti M, Nagarkatti P (2007) Resveratrol (trans-3,5,4′-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Mol Pharmacol 72:1508–1521CrossRef PubMed
    76.Zhang F, Wei W, Chai H, Xie X (2013) Aurintricarboxylic acid ameliorates experimental autoimmune encephalomyelitis by blocking chemokine-mediated pathogenic cell migration and infiltration. J Immunol 190:1017–1025CrossRef PubMed PubMedCentral
  • 作者单位:Min Jung Lee (1) (2)
    Minhee Jang (1) (2)
    Jonghee Choi (10) (2)
    Byung Soo Chang (4)
    Do Young Kim (5)
    Sung-Hoon Kim (1)
    Yi-Seong Kwak (6)
    Seikwan Oh (7)
    Jong-Hwan Lee (8)
    Byung-Joon Chang (8)
    Seung-Yeol Nah (9)
    Ik-Hyun Cho (10) (2) (3)

    1. Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
    2. Department of Convergence Medical Sciences, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
    10. Brain Korea 21 Plus Program, Kyung Hee University, Seoul, 130-701, Republic of Korea
    4. Department of Cosmetology, Hanseo University, Seosan, 356-706, Republic of Korea
    5. Barrow Neurological Institute and St. Joseph’s Medical Center, Phoenix, AZ, 85013, USA
    6. Central Research Institute, Korea Ginseng Corporation, Daejeon, 305-805, Republic of Korea
    7. Department of Neuroscience and Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, 158-710, Republic of Korea
    8. Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Republic of Korea
    9. Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Republic of Korea
    3. Institute of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
  • 刊物主题:Neurosciences; Neurobiology; Cell Biology; Neurology;
  • 出版者:Springer US
  • ISSN:1559-1182
文摘
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.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700