The Role of Mitochondria in Piperine Mediated Cardioprotection in Isoproterenol Induced Myocardial Ischemia

Author(s): Vijaya Padma Viswanadha*, Velumani Dhivya, Bharath Somasundaram, Narasimha Murthy Beeraka, Chih-Yang Huang, Liudmila M. Mikhaleva, Evgeny Achkasov, Sergey Bondarev, Leonid Gridin, Vladimir N. Nikolenko, Gjumrakch Aliev*

Journal Name: Current Pharmaceutical Design

Volume 27 , Issue 26 , 2021


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Abstract:

Background: Several pharmacological therapeutic interventions are being used as therapeutic agents against myocardial infarction/ischemia (MI) but their usage is constrained by toxicity and nonselective pharmacological actions. Our preliminary report depicted the cardioprotective effect of piperine against isoproterenol (ISO)-induced MI.

Aim: Current study determined the protective efficacy of piperine by modulating mitochondrial function in rat models of isoproterenol (ISO)-induced myocardial ischemia.

Methods: The above aim was achieved by analyzing mitochondrial antioxidant status, mitochondrial calcium, mitochondrial enzyme activity, ATP level, and apoptosis. Ultra-structural alterations in heart tissue were determined by TEM analysis. RT-PCR studies and Western blotting were executed to determine apoptotic and proapoptotic gene expression, and apoptotic protein expression, respectively.

Results: The results elucidate that piperine pre-treatment prevents ISO induced alterations in the mitochondrial antioxidant status, Krebs cycle as well as mitochondrial respiratory chain enzyme activities (MRCEs). ISO induced ultrastructural changes of heart mitochondria were significantly reduced in the group that received piperine pretreatment followed by ISO injection. Piperine maintains mitochondrial calcium homeostasis and inhibits ISO-induced myocardial apoptosis. A significant increase in the expression levels of proapoptotic genes such as Bax, caspases (caspase 9, caspase 3), and cytochrome-c with a concomitant decrease in Bcl-2 expression (anti-apoptotic gene) was observed in ISO injected group compared to the control group. The group that received the piperine pretreatment followed by ISO administration showed a significant decrease in the expression profile of proapoptotic genes with a concomitant increase in the anti-apoptotic gene expression than the ISO injected group. Apoptotic protein expressions including Bax, cytochrome-c, caspase-3, and cleaved PARP were upregulated & Bcl-2 was downregulated with ISO treatment, whereas piperine pre-treatment prevented these changes in apoptotic protein expressions during ISO-induced myocardial cell damage.

Conclusion: Current results demonstrate the efficacy of piperine for attenuating ISO-induced myocardial ischemia by enhancing mitochondria function. This study described that piperine could be used as a nutritional intervention against ISO-induced myocardial ischemia.

Keywords: Myocardial infarction, piperine, isoproterenol, mitochondria, ATP, apoptosis.

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Article Details

VOLUME: 27
ISSUE: 26
Year: 2021
Published on: 09 September, 2020
Page: [2975 - 2989]
Pages: 15
DOI: 10.2174/1381612826666200909125750
Price: $65

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