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: Yong Wang, Xianhong Dong, Zhengzhao Li, Wenbo Wang, Jing Tian, Jian Chen
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 339 Issue 1-2 Pg. 144-8 (Apr 15 2014) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 24548484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Estrogen Receptor alpha
• Isoflavones
• MIRN375 microRNA, rat
• MicroRNAs
• Neuroprotective Agents
• Rasd1 protein, rat
• 7,3'-dihydroxy-4'-methoxyisoflavone
• ras Proteins

Topics

• Animals
• Brain Ischemia (metabolism, prevention & control)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects, physiology)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Estrogen Receptor alpha (biosynthesis)
• Isoflavones (pharmacology, therapeutic use)
• Male
• MicroRNAs (biosynthesis)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, prevention & control)
• Treatment Outcome
• Up-Regulation (drug effects, physiology)
• ras Proteins (metabolism)