Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice

被引：32

作者：

Wang, Jun ^{[1
]}

Chen, Fu ^{[1
]}

Zheng, Peng ^{[1
]}

Deng, Weijuan ^{[1
]}

Yuan, Jia ^{[1
]}

Peng, Bo ^{[1
]}

Wang, Ruochen ^{[1
]}

Liu, Wenjun ^{[1
]}

Zhao, Hui ^{[1
]}

Wang, Yanqing ^{[1
]}

Wu, Gencheng ^{[1
]}

机构：

[1] Fudan Univ, WHO Collaborating Ctr Tradit Med,Inst Brain Sci, Dept Integrat Med & Neurobiol,Shanghai Med Coll, State Key Lab Med Neurobiol,Inst Acupuncture Res, Shanghai 200032, Peoples R China

来源：

EXPERIMENTAL NEUROLOGY | 2012年 / 236卷 / 01期

关键词：

Huperzine A; Spinal cord; Multiple sclerosis; Experimental autoimmune encephalomyelitis; Inflammation; Demyelination; CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINESTERASE INHIBITOR; ALZHEIMERS-DISEASE; MODEL; IMMUNOLOGY; DISRUPTION; DONEPEZIL; PROTECTS; ALPHA-7; CCL2;

D O I：

10.1016/j.expneurol.2012.03.024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-gamma and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-gamma and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：79 / 87

页数：9

共 42 条

[11] Current Views on the Roles of Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis [J].

El-behi, Mohamed ;

Rostami, Abdolmohamad ;

Ciric, Bogoljub .

JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2010, 5 (02) :189-197

[12] A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine [J].

Ezoulin, M. J. M. ;

Liu, Z. ;

Dutertre-Catella, H. ;

Wu, G. ;

Dong, C. Z. ;

HeymanS, F. ;

Ombetta, J. E. ;

Rat, P. ;

Massicot, F. .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2007, 7 (13) :1685-1694

[13] Prevention of clinical and histological signs of proteolipid protein (PLP)-induced experimental allergic encephalomyelitis (EAE) in mice by the water-soluble carbon monoxide-releasing molecule (CORM)-A1 [J].

Fagone, P. ;

Mangano, K. ;

Quattrocchi, C. ;

Motterlini, R. ;

Di Marco, R. ;

Magro, G. ;

Penacho, N. ;

Romao, C. C. ;

Nicoletti, F. .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2011, 163 (03) :368-374

[14]

Fu L.M., 2009, ALTERN MED

[15] Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis [J].

Glass, WG ;

Hickey, MJ ;

Hardison, JL ;

Liu, MT ;

Manning, JE ;

Lane, TE .

JOURNAL OF IMMUNOLOGY, 2004, 172 (07) :4018-4025

[16] Huperzine A as Potential Treatment of Alzheimer's Disease: An Assessment on Chemistry, Pharmacology, and Clinical Studies [J].

Ha, Giang T. ;

Wong, Ryan K. ;

Zhang, Yan .

CHEMISTRY & BIODIVERSITY, 2011, 8 (07) :1189-1204

[17] Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors [J].

Hao, Junwei ;

Simard, Alain R. ;

Turner, Gregory H. ;

Wu, Jie ;

Whiteaker, Paul ;

Lukas, Ronald J. ;

Shi, Fu-Dong .

EXPERIMENTAL NEUROLOGY, 2011, 227 (01) :110-119

[18] Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J].

Harrington, LE ;

Hatton, RD ;

Mangan, PR ;

Turner, H ;

Murphy, TL ;

Murphy, KM ;

Weaver, CT .

NATURE IMMUNOLOGY, 2005, 6 (11) :1123-1132

[19] Huperzine A provides neuroprotection against several cell death inducers using in vitro model systems of motor neuron cell death [J].

Hemendinger, Richelle A. ;

Armstrong, Edward J., III ;

Persinski, Rafal ;

Todd, Julianne ;

Mougeot, Jean-Luc ;

Volvovitz, Franklin ;

Rosenfeld, Jeffrey .

NEUROTOXICITY RESEARCH, 2008, 13 (01) :49-61

[20] IL-23 drives a pathogenic T cell population that induces autoimmune inflammation [J].

Langrish, CL ;

Chen, Y ;

Blumenschein, WM ;

Mattson, J ;

Basham, B ;

Sedgwick, JD ;

McClanahan, T ;

Kastelein, RA ;

Cua, DJ .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (02) :233-240

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