title: Neuroprotective effect of 4-methylcyclopentadecanone on focal cerebral ischemia/reperfusion injury in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, China.
authors.forename: Yukui
authors.initials: Y
authors.lastname: Ma
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaomian
authors.initials: X
authors.lastname: Zhou
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007659:Ketones / Q000494:pharmacology* / Q000627:therapeutic use*; D047028:Macrocyclic Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C000589480:4-methylcyclopentadecanone; D007659:Ketones; D047028:Macrocyclic Compounds; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3