title: Beneficial effect of magnesium lithospermate B on cerebral ischemia-reperfusion injury in rats involves the regulation of miR-107/glutamate transporter 1 pathway.
abstract: Recent studies uncovered that glutamate accumulation following cerebral ischemia-reperfusion (I/R) was related to the dysfunction of miR-107/glutamate transporter-1(GLT-1) pathway and magnesium lithospermate B (MLB) possesses the pharmacological activity of anti-excitotoxicity. This study aims to explore whether MLB is able to protect rat brain from excitatory neurotoxicity during I/R by modulating miR-107/GLT-1 pathway. Rats were subjected to 2h of cerebral ischemia following by 24h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score, infarct volume and cellular apoptosis concomitant with glutamate accumulation, miR-107 elevation and GLT-1 down-regulation. Administration of MLB reduced I/R-induced cerebral injury accompanied by a reverse in glutamate accumulation, miR-107 and GLT-1 expression. Next, we examined the association of MLB with miR-107/GLT-1 pathway in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased the nerve cells apoptosis concomitant with glutamate accumulation and miR-107 elevation, and suppressed GLT-1 expression, mimicking our in vivo findings. All these effects were reversed in the presence of MLB, confirming a strong correlation between MLB and miR-107/GLT-1 pathway. Based on these observations, we conclude that MLB is able to protect the rat brain from excitatory neurotoxicity during I/R through the regulation of miR-107/GLT-1 pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Zhong-Bao
authors.initials: ZB
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Kai-Di
authors.initials: KD
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
authors.forename: Jing-Jie
authors.initials: JJ
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Pharmacology, Xiangnan University, Chenzhou 423000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lou
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Electronic address: Junpeng@csu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D004365:Drugs, Chinese Herbal; D027342:Excitatory Amino Acid Transporter 2; C579315:MIRN107 microRNA, rat; D035683:MicroRNAs; D018696:Neuroprotective Agents; C061091:lithospermate B; D018698:Glutamic Acid
keywords: Brain; Glutamate transporter 1; Ischemia–reperfusion; Magnesium lithospermate B; miR-107