title: Matrine protects neuro-axon from CNS inflammation-induced injury.
abstract: Neuro-axonal injury in the central nervous system (CNS) is one of the major pathological hallmarks of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has recently been shown to effectively suppress EAE through an anti-inflammatory mechanism. However, whether MAT can also protect myelin/axons from damage is not known. In the present study we show that, while untreated rats developed severe clinical disease, CNS inflammatory demyelination, and axonal damage, these clinical and pathological signs were significantly reduced by MAT treatment. Consistently, MAT treatment reduced the concentration of myelin basic protein in serum and downregulated expression of β-amyloid (Aβ) and B-site APP cleaving enzyme 1 (BACE-1) in the CNS. Further, the CNS of MAT-treated rats exhibited increased expression of brain-derived neurotrophic factor (BDNF), an important factor for neuronal survival and axonal growth. Together, these results demonstrate that MAT effectively prevented neuro-axonal injury, which can likely be attributed to inhibiting risk factors such as BACE-1 and upregulating neuroprotective factors such as BDNF. We conclude that this novel natural reagent, MAT, which effectively protects neuro-axons from CNS inflammation-induced damage, could be a potential candidate for the treatment of neurodegenerative diseases such as MS.
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: Peng
authors.initials: P
authors.lastname: Lv
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, 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 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*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007887:Fabaceae / Q000737:chemistry; D005260:Female; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000093842:Matrines
chemical_list: D000470:Alkaloids; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D010936:Plant Extracts; D011807:Quinolizines; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D000093842:Matrines
keywords: Axonal injury; EAE; MS; Matrine