Current Pharmaceutical Design

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

Volume: 27Issue: 26

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 and Gjumrakch Aliev*

Affiliation:

• Translational Research Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore-641046, Tamil Nadu,India

• I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), St. Trubetskaya, 8, bld. 2, Moscow, 119991,Russian Federation

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

Abstract:

Background: Several pharmacological therapeutic interventions are being used as therapeutic agentsagainst myocardial infarction/ischemia (MI) but their usage is constrained by toxicity and nonselective pharmacologicalactions. 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 ratmodels 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 determinedby TEM analysis. RT-PCR studies and Western blotting were executed to determine apoptotic andproapoptotic gene expression, and apoptotic protein expression, respectively.

Results: The results elucidate that piperine pre-treatment prevents ISO induced alterations in the mitochondrialantioxidant status, Krebs cycle as well as mitochondrial respiratory chain enzyme activities (MRCEs). ISO inducedultrastructural changes of heart mitochondria were significantly reduced in the group that receivedpiperine pretreatment followed by ISO injection. Piperine maintains mitochondrial calcium homeostasis and inhibitsISO-induced myocardial apoptosis. A significant increase in the expression levels of proapoptotic genessuch 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 receivedthe piperine pretreatment followed by ISO administration showed a significant decrease in the expressionprofile of proapoptotic genes with a concomitant increase in the anti-apoptotic gene expression than theISO injected group. Apoptotic protein expressions including Bax, cytochrome-c, caspase-3, and cleaved PARPwere upregulated & Bcl-2 was downregulated with ISO treatment, whereas piperine pre-treatment prevented thesechanges in apoptotic protein expressions during ISO-induced myocardial cell damage.

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

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Viswanadha Padma Vijaya *, Dhivya Velumani, Somasundaram Bharath , Beeraka Murthy Narasimha , Huang Chih-Yang , Mikhaleva M. Liudmila , Achkasov Evgeny , Bondarev Sergey , Gridin Leonid , Nikolenko N. Vladimir and Aliev Gjumrakch *, The Role of Mitochondria in Piperine Mediated Cardioprotection in Isoproterenol Induced Myocardial Ischemia, Current Pharmaceutical Design 2021; 27 (26) .https://dx.doi.org/10.2174/1381612826666200909125750