piperine and Reperfusion-Injury

Piperine is the key bioactive factor in black pepper, and has been reported to alleviate cerebral ischemic injury. However, the mechanisms underlying its neuroprotective effects following cerebral ischemia remain unclear. In this study, rats were administered vehicle (dimethyl sulfoxide) or piperine, 20 mg/kg, daily for 14 days before focal cerebral artery occlusion. After occlusion for 2 h followed by reperfusion for 24 h. Histological examinations were used to assess whether piperine has a neuroprotective effect in the rat model of cerebral ischemia/reperfusion injury. The levels of proteins in the ischemic penumbra were evaluated by isobaric tags for relative and absolute quantitation-based proteomics. A total of 3687 proteins were identified, including 23 proteins that were highly significantly differentially expressed between the control and piperine groups. The proteomic findings were verified by immunofluorescence and western blot analysis. Interestingly, piperine administration downregulated a number of critical factors in the complement and coagulation cascades, including complement component 3, fibrinogen gamma chain, alpha-2-macroglobulin, and serpin family A member 1. Collectively, our findings suggest that the neuroprotective effects of piperine following cerebral ischemia/reperfusion injury are related to the regulation of the complement and coagulation cascades.

Topics: Alkaloids; Animals; Benzodioxoles; Brain; Brain Ischemia; Male; Neuroprotective Agents; Piperidines; Polyunsaturated Alkamides; Protein Interaction Domains and Motifs; Proteomics; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Piperine is a spice principle, and its protective role against oxidative damage and lipid peroxidation has been reported. In this study, we aimed to investigate the effects of piperine in the prevention of ischemia-reperfusion injury to the small intestine.. Rats were allocated to three groups of 8 rats each. Rats in the sham group underwent laparotomy and observation only. Animals in the control and study groups underwent 45 minutes ischemia followed by 60 minutes reperfusion. In the study group, 10 mg/kg piperine was administered intraperitoneally just before the reperfusion procedure. Blood samples were obtained for measurement of lactate levels, and resection of the terminal ileum was performed to evaluate the histopathologic specimens and tissue malondialdehyde, superoxide dismutase, and glutathione activities. All results were expressed as mean±SD. Comparisons between groups were made by using the one way analysis of variance (ANOVA).. Lactate and malondialdehyde levels were significantly higher in the control group than the study and sham groups (p<0.001). In the study group, superoxide dismutase, and glutathione activities were significantly higher than in the control group (p<0.001). The sham group had the highest activities. Histopathologic examination showed disruption of villous pattern and lamina propria in the control group.. Intraperitoneal administration of 10 mg/kg piperine just before the reperfusion may reduce ischemia-reperfusion injury to the small intestine.

Topics: Alkaloids; Animals; Benzodioxoles; Disease Models, Animal; Glutathione; Ileum; Injections, Intraperitoneal; Ischemic Preconditioning; Lipid Peroxidation; Male; Malondialdehyde; Piperidines; Polyunsaturated Alkamides; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Torsion Abnormality

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.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Benzodioxoles; Cyclooxygenase 2; Cytokines; Down-Regulation; Infarction, Middle Cerebral Artery; Inflammation Mediators; Male; Motor Activity; Muscle Strength; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Reperfusion Injury