title: Matrine regulates glutamate-related excitotoxic factors in experimental autoimmune encephalomyelitis.
abstract: It is increasingly accepted that glutamate excitotoxicity contributes to the death of nerve cells in multiple sclerosis (MS). Matrine (MAT) is a quinolizidine alkaloid that has long been used in the treatment of hepatitis B without obvious side effects. Previous reports have shown that MAT suppresses central nervous system inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however whether MAT effectively inhibits excitotoxic molecules, such as glutamate-related factors, is still unclear. In this study, we provide data showing that MAT attenuated EAE disease severity, accompanied by downregulated glutamate and upregulated GABA levels, as well as enhanced expression of two dependent glutamate transporters (GLT-1 and GLAST). In addition, MAT treatment significantly reduced the level of the NMDA- and AMPA-glutamate receptor in EAE rats. Taken together, our data indicate that MAT treatment regulates glutamate-related molecules, and suggests that the neuroprotective role of MAT is a novel mechanism underlying its therapeutic effect in EAE.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Xu
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Guang-Xian.Zhang@jefferson.edu.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: zhulin66zhulin@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D011807:Quinolizines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000093842:Matrines
keywords: 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propranoic acid receptor; AMPAR; CNS; EAE; GABA; GluTs; Glutamate excitotoxicity; MAT; MS; Matrine; N-methyl-d-aspartic acid receptor; NMDAR; central nervous system; experimental autoimmune encephalomyelitis; glutamate transporters; matrine; multiple sclerosis; γ-aminobutyric acid