Neuroprotective effect of 4-methylcyclopentadecanone on focal cerebral ischemia/reperfusion injury in rats

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. © the japanese pharmacological society.