This study aimed to investigate the anti-inflammatory effect of 4-methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF-α and IL-1β levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF-κB p65 subunit and expression of p-IκBα were investigated by Western blotting. Our results showed that 4-MCPC treatment decreased infarct volume significantly, compared with I/R group (16.8%±7.5% vs. 39.7%±10.9%); it reduced MPO activity (0.43 ± 0.10 vs. 1.00 ± 0.51 U/g) and expression levels of TNF-α (18.90 ± 3.65 vs. 35.87 ± 4.87 ng/g) and IL-1β (1.68 ± 0.23 vs. 2.67 ± 0.38 ng/g) in ischemic brain tissues of rats. Further study revealed that 4-MCPC treatment markedly reduced nuclear translocation of NF-κB p65 subunit and expression of p-IκBα in ischemic cerebral cortex. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury and displays anti-inflammatory actions through inhibition of the NF-κB signal pathway.
Keywords: 4-methylcyclopentadecanone; IL-1β; NF-κB; TNF-α; inflammation; ischemia/reperfusion.
© 2018 Société Française de Pharmacologie et de Thérapeutique.