Cardioprotective effect of Perakine against myocardial ischemia-reperfusion injury of type-2 diabetic rat in Langendorff-Perfused Rat Hearts: Role of TLR4/NF-kB signalling pathway.

Abstract

Myocardial ischemia-reperfusion (I/R) injury is a grave life-threatening situation, if not treated well in time. The development of natural remedies for myocardial I/R injury has witnessed dramatic growth in the last decade. Prompted by the above, in the present study, we have elucidated the pharmacological effect of Perakine (PER), an indole alkaloid in myocardial ischemia-reperfusion injury in type 2 diabetic rats. The model was established by inducing diabetes in experimental rats followed by the development of myocardial I/R injury model of isolated rat heart by the use of improved Langendorff retrograde perfusion technology. Results of the study suggest that PER significantly lowered the infarct size and infarct volume, and improvement in cardiac ability (LVSP, ±dP/dtmax, and heart rate). It also showed a significant lowering of cardiac biomarkers (CK, CK(MB), ALT, AST, and LDH) in a dose-dependent manner as compared to unprotected IR rats. The level of oxidative stress (MDA, SOD, and GSH) was also found lowered in IR rats together with a reduction in the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α). The anti-inflammatory acting of PER on IR rats is believed to be linked with the reduction of TNF-α, NF-κB, and TLR4 in both RT-qPCR and western blot analysis. Our research showed that Perakine could potentially alleviate cardiac ischemia-reperfusion injury in rats by blocking the TLR4/NF-κB signaling cascade.