Alpha-pinene modulates inflammatory response and protects against brain ischemia via inducible nitric oxide synthase-nuclear factor-kappa B-cyclooxygenase-2 pathway

Abstract

Backgrounds: Cerebral ischemia-reperfusion leads to brain tissue injury. Inflammation and apoptosis play pivotal roles in the pathology.

Objective: α-Pinene is an organic compound of many aromatic plants and is known as a potent agent to possess antioxidant, and anti-inflammatory properties. Here, we sought to identify the anti-inflammatory and anti-apoptosis mechanism by which α-Pinene improves brain ischemia injury.

Results: Male Wistar rats underwent MCAO surgery for 1 h and different doses of alpha-pinene (25, 50, and 100 mg/kg) were intraperitoneally injected immediately after reperfusion to test this hypothesis. IV, NDS, gene and protein expression of inducible nitric oxide synthase (iNOS), cyclogenase-2 (COX-2), nuclear factor kappa B (NF-κB) p65, and caspase-3 were assessed 24 h after reperfusion. Results demonstrated that NF-κB p65, iNOS, and COX-2 gene and protein expression increased in the hippocampus, cortex, and striatum after 24 h of reperfusion, and alpha-pinene significantly inhibited NF-kB p65, iNOS, and COX-2 expression. Also, alpha-pinene significantly reduced the ischemia/reperfusion-induced caspase-3 activation in CA1 area of hippocampus.

Conclusion: Results showed that alpha-pinene protects the cerebral against ischemic damage caused by MCAO, and this effect may be through the regulating iNOS -NF-kappa B- COX-2 and caspase-3 inflammatory and apoptotic pathways.

Keywords: Alpha-pinene; Caspase-3; Inflammatory response; Ischemic stroke; NF-kappa B.