title: Matrine suppresses expression of adhesion molecules and chemokines as a mechanism underlying its therapeutic effect in CNS autoimmunity.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a classical experimental model of multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). Previous reports have suggested that matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, could inhibit clinical EAE, but its mechanism of action is not clear. Our present study showed that MAT treatment resulted in dose-dependent reduction in neurological scores. Consistent with this observation, infiltration of inflammatory cells and demyelination in the CNS were also significantly suppressed. We further studied the mechanism underlying these effects of MAT by determining whether this treatment influences expression of molecules that are involved in the activation and migration of inflammatory cells. Our results showed that MAT significantly inhibited expression and production in the CNS of ICAM-1 and VCAM-1, key adhesive molecules, and CCL3 and CCL5, key chemokines, that attract inflammatory cells into the CNS. Furthermore, the TLR4/MD2 pathway, which plays an important role in the induction of Th1/Th17 cells in EAE, was also significantly inhibited. Together, our study not only demonstrates that MAT may be a novel therapeutic option for the treatment for MS, but also provides further information on mechanisms underlying the effect of MAT treatment.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
mesh_terms: D031841:Aconitum / Q000276:immunology; D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011807:Quinolizines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D011807:Quinolizines; D051197:Toll-Like Receptor 4; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000093842:Matrines
references.citation: J Leukoc Biol. 1997 Nov;62(5):681-7
references.pmid: 9365124
references.citation: Acta Neuropathol. 2012 Oct;124(4):491-503
references.pmid: 22526024
references.citation: J Immunol. 2010 Aug 15;185(4):2563-9
references.pmid: 20631308
references.citation: J Immunol. 2006 Apr 1;176(7):4399-409
references.pmid: 16547278
references.citation: Int Immunopharmacol. 2008 Dec 20;8(13-14):1767-72
references.pmid: 18775799
references.citation: J Neuroimmunol. 1993 Sep;47(2):133-40
references.pmid: 8103775
references.citation: J Neurol Sci. 2005 Feb 15;228(2):210-4
references.pmid: 15694210
references.citation: J Clin Invest. 1999 Mar;103(6):807-15
references.pmid: 10079101
references.citation: Mult Scler. 2000 Feb;6(1):3-13
references.pmid: 10694839
references.citation: J Neural Transm (Vienna). 2006 Apr;113(4):477-85
references.pmid: 16550326
references.citation: Nat Immunol. 2008 Sep;9(9):970-80
references.pmid: 18711434
references.citation: World J Gastroenterol. 2004 Nov 15;10(22):3269-73
references.pmid: 15484298
references.citation: Adv Exp Med Biol. 1993;331:243-8
references.pmid: 8333339
references.citation: J Neuroinflammation. 2012 Oct 30;9:248
references.pmid: 23111144
references.citation: J Clin Invest. 2010 Jan;120(1):90-2
references.pmid: 20038805
references.citation: Ann N Y Acad Sci. 2012 Jan;1247:117-37
references.pmid: 22224673
references.citation: Biochim Biophys Acta. 2011 Feb;1812(2):220-30
references.pmid: 20692338
references.citation: Am J Chin Med. 2011;39(5):933-41
references.pmid: 21905283
references.citation: Immunol Rev. 2012 Jul;248(1):140-55
references.pmid: 22725959
references.citation: Biol Pharm Bull. 2010;33(1):40-6
references.pmid: 20045933
references.citation: Annu Rev Pathol. 2012;7:185-217
references.pmid: 22313379
references.citation: J Neuroimmunol. 1993 Mar;43(1-2):15-21
references.pmid: 8096220
references.citation: Adv Exp Med Biol. 2012;946:237-51
references.pmid: 21948372
references.citation: Brain. 2006 Aug;129(Pt 8):1972-83
references.pmid: 16714315
references.citation: J Immunol. 2007 Jan 15;178(2):851-7
references.pmid: 17202346
references.citation: CNS Neurosci Ther. 2012 Nov;18(11):909-17
references.pmid: 22994384
references.citation: Immunol Rev. 2000 Oct;177:52-67
references.pmid: 11138785
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13064-9
references.pmid: 22826216
references.citation: Cell Mol Biol (Noisy-le-grand). 2005 Sep 05;51(3):337-42
references.pmid: 16191402
references.citation: Am J Chin Med. 2010;38(2):265-77
references.pmid: 20387224