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

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, Western blotting were executed to determine apoptotic & 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 ultra-structural changes of heart mitochondria were significantly reduced in the group 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), cytochrome-c with concomitant decrease in Bcl-2 expression (anti-apoptotic gene) was observed in ISO injected group compared to control group. Group received the piperine pretreatment followed by ISO administration has showed a significant decrease in the expression profile of proapoptotic genes with concomitant increase in the anti-apoptotic gene expression than 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 piperine efficacy for attenuating ISO-induced myocardial ischemia by enhancing mitochondria function. This study described that the piperine could be used as a nutritional intervention against ISO-induced myocardial ischemia.

Keywords: ATP; Isoproterenol; Myocardial infarction; apoptosis; mitochondria; piperine.