PMID- 25576296 OWN - NLM STAT- MEDLINE DCOM- 20150521 LR - 20221207 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 98 IP - 1 DP - 2015 Feb TI - Matrine protects neuro-axon from CNS inflammation-induced injury. PG - 124-30 LID - S0014-4800(15)00003-9 [pii] LID - 10.1016/j.yexmp.2015.01.001 [doi] AB - 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 beta-amyloid (Abeta) 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Kan, Quan-Cheng AU - Kan QC AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Lv, Peng AU - Lv P AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhang, Xiao-Jian AU - Zhang XJ AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Xu, Yu-Ming AU - Xu YM AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhang, Guang-Xian AU - Zhang GX AD - Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: guang-xian.zhang@jefferson.edu. FAU - Zhu, Lin AU - Zhu L AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: zhulin66zhulin@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150107 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Alkaloids) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Plant Extracts) RN - 0 (Quinolizines) RN - 0 (RNA, Messenger) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (Bace1 protein, rat) RN - 0 (Matrines) SB - IM MH - Alkaloids/*pharmacology MH - Amyloid Precursor Protein Secretases/genetics/metabolism MH - Animals MH - Aspartic Acid Endopeptidases/genetics/metabolism MH - Axons/*drug effects/metabolism/*pathology MH - Biomarkers/analysis MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cells, Cultured MH - Central Nervous System/*drug effects/metabolism/pathology MH - Encephalomyelitis, Autoimmune, Experimental/*drug therapy/immunology/pathology MH - Enzyme-Linked Immunosorbent Assay MH - Fabaceae/chemistry MH - Female MH - Immunoenzyme Techniques MH - Inflammation/immunology/pathology/*prevention & control MH - Plant Extracts/*pharmacology MH - Quinolizines/*pharmacology MH - RNA, Messenger/genetics MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Matrines OTO - NOTNLM OT - Axonal injury OT - EAE OT - MS OT - Matrine EDAT- 2015/01/13 06:00 MHDA- 2015/05/23 06:00 CRDT- 2015/01/11 06:00 PHST- 2014/12/16 00:00 [received] PHST- 2015/01/05 00:00 [accepted] PHST- 2015/01/11 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/05/23 06:00 [medline] AID - S0014-4800(15)00003-9 [pii] AID - 10.1016/j.yexmp.2015.01.001 [doi] PST - ppublish SO - Exp Mol Pathol. 2015 Feb;98(1):124-30. doi: 10.1016/j.yexmp.2015.01.001. Epub 2015 Jan 7.