Abstract

Network pharmacological analysis can be an effective solution for the challenges in drug discovery. Many bioactive-target combinations have been experimentally studied. In the present study, the combination of Resveratrol, Lipoic acid and Coenzyme Q₁₀, having a multifaceted target in cardiac cells was utilized to attenuate ischemia-reperfusion injury in statin-treated rats. Langendorff model of Ischemia-Reperfusion (30 min ischemia+60 min reperfusion) was used in the study where the efficacy of combination drug was compared between normal and statin-treated hearts. The combination drugs were administered as preconditioning agents, prophylactic and therapeutic agents.  Cardiac biochemical parameters like haemodynamic, injury, oxidative stress and mitochondrial parameters were assessed. Ischemia Reperfusion imparted significantly higher adverse outcomes in statin-treated rat hearts as compared with the normal heart which was attributed to severe mitochondrial damage. Administration of combination drugs attenuated cardiac injury and mediated the physiological recovery effectively in all Ischemia-Reperfusion challenged experimental groups with varying degrees of efficiency. Preconditioning the isolated rat heart with a combination drug provides the least protection when compared with a therapeutic and prophylactic mode of treatments where the latter render higher protection. Improved mitochondrial activity and reduction in oxidative stress supports the protective ability of combination drug in all experimental groups.