1. Harnessing the mitochondrial integrity for neuroprotection: Therapeutic role of piperine against experimental ischemic stroke.
- Author
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Kaushik P, Ali M, Salman M, Tabassum H, and Parvez S
- Subjects
- Alkaloids pharmacology, Animals, Benzodioxoles pharmacology, Brain Ischemia metabolism, Brain Ischemia pathology, Cell Survival drug effects, Cell Survival physiology, Cytochrome P-450 Enzyme Inhibitors pharmacology, Cytochrome P-450 Enzyme Inhibitors therapeutic use, Ischemic Stroke metabolism, Ischemic Stroke pathology, Male, Mitochondria metabolism, Neuroprotection physiology, Neuroprotective Agents pharmacology, Piperidines pharmacology, Polyunsaturated Alkamides pharmacology, Rats, Rats, Wistar, Alkaloids therapeutic use, Benzodioxoles therapeutic use, Brain Ischemia prevention & control, Ischemic Stroke prevention & control, Mitochondria drug effects, Neuroprotection drug effects, Neuroprotective Agents therapeutic use, Piperidines therapeutic use, Polyunsaturated Alkamides therapeutic use
- Abstract
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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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