Neuroprotective Effect of 4-Methylcyclopentadecanone on Focal Cerebral Ischemia/Reperfusion Injury in Rats

Journal of Pharmacological Sciences

Chunxia Zhang²  Xiaomian Zhou¹  Yukui Ma¹  Yue Li³  Yingliang Wu¹ 

[1] Department of Pharmacology, Shenyang Pharmaceutical University, China;Jinan Maternal and Child Health Hospital, China;People’s Hospital of Zhangqiu City, China

关键词: 4-methylcyclopentadecanone;    apoptosis;    Akt;    GSK-3β;    ischemia/reperfusion;   

DOI  :  10.1254/jphs.14102FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(3)The present study aimed to investigate the effect of 4-methylcyclopentadecanone (4-MCPC) on local cerebral ischemia–reperfusion and the possible mechanisms involved. For this purpose, the focal cerebral ischemia rat model was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (4 or 8 mg·kg�?1, p.o.) just 0.5 h before reperfusion. The neurological deficit scores and the ischemic infarct volume were recorded 24 h after the MCAO. In addition, the number of apoptotic cells was measured by TUNEL assay, and the expression of apoptosis-regulatory proteins and the PI3K/Akt neuroprotective signaling pathway were investigated by western blotting. Our results indicated that 4-MCPC (4 or 8 mg·kg�?1) remarkably alleviated cerebral I/R injury by decreasing infarct volume and neurological deficit scores. 4-MCPC also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that 4-MCPC treatment also increased the level of p-Akt and p-GSK-3β. Wortmannin (PI3K inhibitor) markedly abolished the effects of 4-MCPC. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury through the inhibition of apoptosis, and this neuroprotective effect may be partly related to the activation of the PI3K/Akt signal pathway.

【 授权许可】

Unknown