Protective effect of 4-methyl-2-{[4-(toluene-4-sulfonyl)-thiomorpholine-3-carbonyl]-amino}-pentanoic acid isopropyl ester against cerebral ischemia

作     者：Tinghui Zhang Yihan Wang Xin Li Jinwei Dai Quankun Zhuang Xirui Song Junhai Xiao Lili Wang Yuyang Zhang 

作者机构：School of Life Science and BiopharmaceuticsShenyang Pharmaceutical UniversityShenyang 110016China Laboratory of Computer-Aided Drug Design&DiscoveryState Key Laboratory of Toxicology and Medical CountermeasuresInstitute of Pharmacology and ToxicologyAcademy of Military Medial SciencesBeijing 100850China Laboratory of the drug screeningInstitute of Pharmacology and ToxicologyAcademy of Military Medial SciencesBeijing 100850China 

出 版 物：《Asian Journal of Traditional Medicines》 (亚洲传统医药（英文）)

年 卷 期：2021年第16卷第3期

页      面：139-152页

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：This work is supported by a grant from the national science and technology major project a candidate drug for neurodegenerative diseases targeting FKBPs (2009ZX09103-024) 

主　　题：HD5-6 global ischemia focal ischemia MDA BDNF VEGF 

摘      要：To investigate the effects of 4-methyl-2-{[4-(toluene-4-sulfonyl)-thiomorpholine-3-carbonyl]-amino}-pentanoic acid isopropyl ester(HD5-6)against cerebral ischemia in rodents,the models with global and focal ischemia were induced by bilateral common carotid artery occlusion plus hypotension(BCAOH)and permanent cerebral artery occlusion(p-MCAO)in mice(n=10–12 per group in BCAOH;n=8 per group in p-MCAO)and rats(n=10-11 in each group).HD5-6 prolonged lifetime and improved neurological *** deficits score in HD5-6(30 mg/kg)decreased ***(MDA)in HD5-6-treated mice with ischemia considerably *** infarction volume of the HD5-6-treated rats with MCAO-induced ischemia decreased significantly in the high dose group(P0.05,*** P0.01,i.v.).Immunohistochemistry showed that Brain derived neurotrophic factor(BDNF)in the ipsilateral hemisphere increased and Vascular endothelial growth factor(VEGF)decreased with HD5-6 ***5-6 has protective effects against experimental cerebral ischemia in rodents and the action mechanism may involve anti-oxidation and neurogenesis.