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.

Abstract

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.

• Authors: Kumar Vaibhav, Pallavi Shrivastava, Hayate Javed, Andleeb Khan, Md Ejaz Ahmed, Rizwana Tabassum, Mohd Moshahid Khan, Gulrana Khuwaja, Farah Islam, M Saeed Siddiqui, Mohammed M Safhi, Fakhrul Islam
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 367 Issue 1-2 Pg. 73-84 (Aug 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 22669728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Anti-Inflammatory Agents
• Benzodioxoles
• Cytokines
• Inflammation Mediators
• NF-kappa B
• Neuroprotective Agents
• Piperidines
• Polyunsaturated Alkamides
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• piperine

Topics

• Alkaloids (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Benzodioxoles (pharmacology)
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokines (blood, metabolism)
• Down-Regulation (drug effects)
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
• Inflammation Mediators (blood)
• Male
• Motor Activity (drug effects)
• Muscle Strength (drug effects)
• NF-kappa B (genetics, metabolism)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Piperidines (pharmacology)
• Polyunsaturated Alkamides (pharmacology)
• Rats
• Rats, Wistar
• Reperfusion Injury (etiology, pathology, prevention & control)