Osthole, a Natural Coumarin Improves Cognitive Impairments and BBB Dysfunction After Transient Global Brain Ischemia in C57 BL/6J Mice: Involvement of Nrf2 Pathway

被引:47
作者
Chen, ZiWei [1 ,2 ]
Mao, XueXuan [1 ,2 ]
Liu, AnMin [3 ]
Gao, XiaoYun [4 ]
Chen, XiaoHong [5 ]
Ye, MinZhong [1 ,6 ]
Ye, JianTao [1 ]
Liu, PeiQing [1 ]
Xu, SuoWen [1 ]
Liu, JianXin [7 ]
He, Wei [7 ]
Lian, QiShen [7 ]
Pi, RongBiao [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510080, Guangdong, Peoples R China
[2] Int Joint Lab SYSU PolyU HK Novel Anti Dementia D, Guangzhou 510006, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurosurg, Guangzhou 510080, Guangdong, Peoples R China
[4] Guangzhou Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anesthesiol, Guangzhou 510120, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Neurol, Guangzhou 510080, Guangdong, Peoples R China
[6] Guangdong Inst Sci & Tech Informat, Guangzhou 510080, Guangdong, Peoples R China
[7] Gannan Med Coll, Dept Pharmacol, Ganzhou 310036, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Cerebral ischemia; Osthole; Blood-brain barrier; Oxidative stress; Nrf2; HO-1; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; HEME OXYGENASE-1; NEURONAL DEATH; BARRIER; INDUCTION; MODEL; DAMAGE; EXPRESSION; OCCLUSION;
D O I
10.1007/s11064-014-1483-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke. However, the mechanism underlying the protective effect remains vague. In this study we aimed to investigate the effect of osthole on transient cerebral ischemia as well as its mechanism(s) in C57 BL/6 J mice. Mice were subjected to transient global cerebral ischemia induced by bilateral common carotid artery occlusion for 25 min. Behavioral test was performed at 4 days after ischemia, followed by assessment of neuronal loss in hippocampal CA1 region. Osthole significantly improved the cognitive ability and enhanced the survival of pyramidal neurons in the CA1 region of mice after lesion. Further studies showed that osthole attenuated the permeation of BBB, which may contribute to antioxidative effect by increasing the superoxide dismutase activity and decreasing the malondialdehyde level in model mice. Further studies revealed that osthole obviously up-regulated the protein levels of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 in HT22 cells. In conclusion, our findings indicated that osthole exerts neuroprotective effects against global cerebral ischemia injury by reducing oxidative stress injury and reserving the disruption of BBB, which may be attributed to elevating the protein levels of Nrf2 and HO-1.
引用
收藏
页码:186 / 194
页数:9
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