Cardioprotective Potential of Resveratrol Alone and in Combination with Piperine on Isoproterenol-induced Myocardial Infarction in Rat: Investigation on Oral Bioavailability of Resveratrol

Background: Resveratrol (3,4,5-trihydroxystilbene), a polyphenol derived from plant sources, despite its cardioprotective properties, has limited therapeutic impact due to its low in vivo bioavailability and rapid metabolism, which are major barriers to its effectiveness. Piperine, a nitrogenous substance, has well-established bioenhancer activity and cardioprotective potential. The objective of the study was to investigate the cardioprotective potential of resveratrol and piperine on isoproterenol-induced myocardial infarction in rats, both alone and in combination and to assess the oral bioavailability of resveratrol when co-administered with piperine. Materials and Methods: Resveratrol, piperine, and their combinations (20 mg/kg, oral) were administered to rats as pre-treatments for 28 days. Myocardial infarction was induced by giving isoproterenol (85 mg/kg) subcutaneously. Pharmacokinetic parameters were analyzed by UFLC using rat plasma. The chromatographic separation was achieved on Eclipse plus C18 Column (25 cm x 5 cm x 4.6 mu) with L1 packing using mobile phase containing mixer of milli Q water and methanol (30:70% v/v) at a flow rate of 1 mL/min. Results: The treatment group exhibited a considerable (p<0.001) improvement in heart rate, biomarker, antioxidant, and histological changes compared to the isoproterenol group, confirming the effectiveness of resveratrol. A significant improvement in pharmacokinetic parameters of resveratrol was observed in plasma samples of animals treated with a combination, as compared to those treated with resveratrol alone. Conclusion: The combination of resveratrol and piperine significantly reduced the risk of myocardial infarction induced by isoproterenol when compared to the group that received resveratrol alone. This effect can be attributed to the cardioprotective potential of resveratrol and piperine, as well as piperine's ability to enhance the oral bioavailability of resveratrol.