Piperine suppresses cerebral ischemia–reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model
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The pathophysiological mechanisms leading to neuronal injury in middle cerebral artery occlusion (MCAO) model of cerebral stroke are complex and multifactorial that form the bases of behavioral deficits and inflammation mediated damage. The present study demonstrates the effect of piperine pretreatment (10 mg/kg b wt, once daily p.o. for 15 days) on cerebral ischemia-induced inflammation in male Wistar rats. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 h. A maximum infarct volume (57.80 %) was observed in ischemic MCAO group. However, piperine administration prior to ischemia showed a significant reduction in infarct volume (28.29 %; p < 0.05) and neuronal loss (12.72 %; p < 0.01). As a result of piperine pretreatment, a significant improvement in behavioral outputs of MCAO rats (p < 0.05–0.01) was observed. Piperine successfully reduced the level of proinflammatory cytokines IL-1β, IL-6 and TNF-α, in ischemic group (p < 0.01). Ischemic group brain has shown edematous morphology with vacuolated architecture and pyknotic nuclei in H & E staining which was successfully ameliorated by piperine administration. Moreover, piperine also succeeded in lowering the expression of COX-2, NOS-2, and NF-κB (p < 0.01). Both cytosolic and nuclear NF-κB were down-regulated in ischemic group pre-administered with piperine (p < 0.01). The present study suggests that piperine is able to salvage the ischemic penumbral zone neurons by virtue of its anti-inflammatory property, thereby limiting ischemic cell death.
KeywordsBehavioral deficit COX-2 MCAO NF-κB NOS-2 Piperine
The authors sincerely acknowledge UGC, Govt. of India for providing financial support. Moreover, we thank Dr. Anurag Agrawal, Mr. Tanveer Ahmad and Mr. Manish Kumar (Centre of Excellence for Translational Research in Asthma & Lung disease, Institute of Genomics and Integrative Biology, A unit of C.S.I.R., Mall Road, New Delhi 110007, India) for their valuable suggestion and help in microscopic imaging. We highly appreciate Mr. Dharamvir Singh, Mr. S. Abdul Fitr and Late Mr. Anil Kumar for their technical assistance.
Conflict of interest
The authors declare that there is no conflict of interest. No author has any financial interest or conflict of interest involved with this study.
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