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
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.