Berberine Attenuates Experimental Autoimmune Encephalomyelitis in C57 BL/6 Mice

被引:95
作者
Ma, Xiaomeng [1 ]
Jiang, Ying [1 ]
Wu, Aimin [1 ]
Chen, Xiaohong [1 ]
Pi, Rongbiao [2 ]
Liu, Mei [1 ]
Liu, Yingying [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, Guangzhou, Peoples R China
[2] Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Guangzhou, Peoples R China
来源
PLOS ONE | 2010年 / 5卷 / 10期
基金
中国国家自然科学基金;
关键词
BLOOD-BRAIN-BARRIER; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MATRIX-METALLOPROTEINASE EXPRESSION; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; PLASMINOGEN-ACTIVATOR; TISSUE INHIBITORS; SPINAL-CORD; IN-VITRO; CELLS;
D O I
10.1371/journal.pone.0013489
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects. However, there are no reports about the effects and mechanisms of berberine in experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Methodology/Principal Findings: Female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with berberine at the day of disease onset and medication was administered daily until mice were sacrificed. Blood-brain barrier (BBB) permeability and the alteration of matrix metalloproteinase-2 (MMP-2, 72 kDa) and matrix metalloproteinase-9 (MMP-9, 92 kDa) in the brain and cerebrospinal fluid (CSF) of EAE mice were detected by quantitative measurement for Evan's blue (EB) content, Western blot and gelatin zymography respectively. The results showed that berberine attenuated clinical and pathological parameters of EAE, reduced the permeability of BBB, inhibited the activity and expression of MMP-9 but not MMP-2 in the CSF and brain of EAE mice. Conclusions/Significance: These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration. We think that berberine might be a potential therapeutic agent for MS.
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页数:8
相关论文
共 56 条
[1]   Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS [J].
Anthony, DC ;
Miller, KM ;
Fearn, S ;
Townsend, MJ ;
Opdenakker, G ;
Wells, GMA ;
Clements, JM ;
Chandler, S ;
Gearing, AJH ;
Perry, VH .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 87 (1-2) :62-72
[2]   Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes [J].
Avolio, C ;
Ruggieri, M ;
Giuliani, F ;
Liuzzi, GM ;
Leante, R ;
Riccio, P ;
Livrea, P ;
Trojano, M .
JOURNAL OF NEUROIMMUNOLOGY, 2003, 136 (1-2) :46-53
[3]   MATRIX METALLOPROTEINASES - A REVIEW [J].
BIRKEDALHANSEN, H ;
MOORE, WGI ;
BODDEN, MK ;
WINDSOR, LJ ;
BIRKEDALHANSEN, B ;
DECARLO, A ;
ENGLER, JA .
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE, 1993, 4 (02) :197-250
[4]  
Brown KA, 2001, INT IMMUNOPHARMACOL, V1, P2043
[5]   Berberine inhibits the expression of TNFα, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARγ pathway [J].
Chen, F. L. ;
Yang, Z. H. ;
Liu, Y. ;
Li, L. X. ;
Living, W. C. ;
Wang, X. C. ;
Zhou, W. B. ;
Yang, Y. H. ;
Hu, Ren-Ming .
ENDOCRINE, 2008, 33 (03) :331-337
[6]   Combined treatment with minocycline and prednisone attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice [J].
Chen, Xiaohong ;
Hu, Xueqiang ;
Zou, Yan ;
Pi, Rongbiao ;
Liu, Mei ;
Wang, Tieqiao ;
Zheng, Xueping ;
Liu, Meng ;
Lin, Mingdong ;
Liu, Peiqing ;
Tao, Liang .
JOURNAL OF NEUROIMMUNOLOGY, 2009, 210 (1-2) :22-29
[7]  
Conant K, 1999, ANN NEUROL, V46, P391, DOI 10.1002/1531-8249(199909)46:3<391::AID-ANA15>3.0.CO
[8]  
2-0
[9]   Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions [J].
Cossins, JA ;
Clements, JM ;
Ford, J ;
Miller, KM ;
Pigott, R ;
Vos, W ;
VanderValk, P ;
DeGroot, CJA .
ACTA NEUROPATHOLOGICA, 1997, 94 (06) :590-598
[10]   The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution [J].
Cuzner, ML ;
Gveric, D ;
Strand, C ;
Loughlin, AJ ;
Paemen, L ;
Opdenakker, G ;
Newcombe, J .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1996, 55 (12) :1194-1204