piperine and Brain-Ischemia

Ischemic stroke (IS) is a rapidly increasing global burden and is associated with severe neurological decline and mortality. There is urgent requirement of the efforts, aimed to identify therapeutic strategies that are effective in clinic to promote significant recovery from IS. Studies have shown that mitochondria mediated neuroprotection can be a competent target against ischemic damage. Therefore, we examined whether mitochondrial impairment is regulated by Piperine (PIP), an alkaloid of Piper Longum, which has neuroprotective activity against ischemic brain injury. In this study, transient middle cerebral artery occlusion (tMCAO) surgery was performed on male Wistar rats for 90 min followed by 22.5 h of reperfusion for mimicking the IS condition. This study consisted of three groups: sham, tMCAO and tMCAO + PIP (10 mg/kg b.wt., p.o/day for 15 days), and studied for behavioral tests, infarct volume, brain pathological changes, mitochondrial dysfunction, inflammation alongwith cell survival status. PIP pre-treatment showed reduction in neurological alterations and infarct volume. In addition, PIP pre-treatment suppressed the mitochondrial dysfunction and might have anti-apoptotic potential by preventing Cytochrome c (Cyt c) release from mitochondria to cytoplasm and caspase 3 activation. It also regulates pro-apoptotic, Bax and anti-apoptotic, Bcl-2 proteins accompanied by glial fibrillary acidic protein (GFAP) positive cells in cortex region. Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR) results also showed that PIP reduced the expression of pro-inflammatory protein, interleukin-1 β (IL-1β) and enhanced cell survival by restoring the activity of brain derived neurotrophic factor (BDNF) and its transcription protein, cAMP response element binding protein (CREB). Taken together, PIP reduced the mitochondrial dysfunction, neurological impairment, and enhanced neuronal survival. In conclusion, our findings reinforce PIP as an effective neuroprotective agent and provide important evidence about its role as a potential target to serve as a promising therapy for treatment of IS.

Topics: Alkaloids; Animals; Benzodioxoles; Brain Ischemia; Cell Survival; Cytochrome P-450 Enzyme Inhibitors; Ischemic Stroke; Male; Mitochondria; Neuroprotection; Neuroprotective Agents; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar

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