title: Downregulated RASD1 and upregulated miR-375 are involved in protective effects of calycosin on cerebral ischemia/reperfusion rats.
abstract: Isoflavone calycosin is a typical phytoestrogen extracted from Chinese medical herb Radix Astragali. It has been reported that estrogens could provide neuroprotective effects, and dietary intake of phytoestrogens could reduce stroke injury in cerebral ischemia/reperfusion (I/R) animal models. In the present study, we investigate the molecular mechanisms underlying the neuroprotective effects of calycosin on middle cerebral artery occlusion (MCAO) rats. Focal cerebral ischemia was induced in male rats by MCAO, neurological deficits and brain edema was evaluated after 24h of reperfusion. The results shown calycosin significantly reduced the infarcted volume and the brain water content, and improved the neurological deficit. To provide insight into the functions of estrogen receptor (ER)-mediated signaling pathway in neuroprotection by calycosin, the expression of miR-375, ER-α, RASD1 (Dexamethasone-induced Ras-related protein 1) and Bcl-2 was determined by RT-PCR or western blot assay. Calycosin exhibited a downregulation of RASD1, and an upregulation of ER-α, miR-375 and Bcl-2. Our finding illustrated that calycosin had been shown neuroprotective effects in cerebral ischemia/reperfusion rats, and the molecular mechanisms may correlate with the positive feedback between ER-α and miR-375, along with the regulation of downstream targets.
authors.affiliation: Department of Physiology, Guilin Medical University, Guilin 541004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Xianhong
authors.initials: X
authors.lastname: Dong
authors.affiliation: Emergency Department, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.
authors.forename: Zhengzhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Guilin Medical University, Guilin 541004, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology, Guilin Medical University, Guilin 541004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China. Electronic address: guilinchenjian@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha; D007529:Isoflavones; C574979:MIRN375 microRNA, rat; D035683:MicroRNAs; D018696:Neuroprotective Agents; C528215:Rasd1 protein, rat; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D018631:ras Proteins
keywords: Apoptosis; Calycosin; ER-α; Ischemia/reperfusion; RASD1; miR-375