title: Matrine promotes NT3 expression in CNS cells in experimental autoimmune encephalomyelitis.
abstract: Neurotrophin 3 (NT3) is a potent neurotrophic factor for promoting remyelination and recovery of neuronal function; upregulation of its expression in the central nervous system (CNS) is thus of major therapeutic importance for neurological deficits. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescent, has been recently reported to effectively ameliorate clinical signs in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by secreting antiinflammatory cytokines. In the present study, our goal was to investigate whether MAT could affect NT3 expression of glial cells in the CNS, the major cell populations in the CNS foci of MS/EAE. We found that MAT markedly upregulated NT3 expression in the CNS not only by microglia/macrophages and astrocytes, but also by oligodendrocyte precursor cells, indicative of both paracrine and autocrine effects on myelinating cells. While MAT treatment reduced the numbers of iNOS+M1, but increased Arg1+M2 microglia/macrophage phenotypes, NT3 expression was upregulated in both phenotypes. These results indicate that MAT therapy for EAE acts, at least in part, by stimulating local production of NT3 by glial cells in the CNS, which protects neural cells from CNS inflammation-induced tissue damage.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wen-Di
authors.initials: WD
authors.lastname: Ma
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, Henan, China. Electronic address: zhulin66zhulin@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism*; D011807:Quinolizines / Q000008:administration & dosage*; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D000093842:Matrines
chemical_list: D000470:Alkaloids; D018836:Inflammation Mediators; D020933:Neurotrophin 3; D011807:Quinolizines; D000093842:Matrines
keywords: Arg1; Experimental autoimmune encephalomyelitis; Matrine; NT3; iNOS