Cardioprotective effect of perakine against myocardial ischemia-reperfusion injury of type-2 diabetic rat in Langendorff-perfused rat hearts: the role of TLR4/NF-κB signaling pathway.

Abstract

Myocardial ischemia-reperfusion (I/R) injury is a grave life-threatening situation if not promptly treated. 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 a myocardial I/R injury model in isolated rat hearts using an improved Langendorff retrograde perfusion technique. The results of the study suggest that PER significantly lowered the infarct size and volume, with an improvement in cardiac ability (LVSP, ± dP/dtmax, and heart rate). It also significantly lowered cardiac biomarkers (CK, CK[MB], ALT, AST, and LDH) in a dose-dependent manner compared to unprotected I/R rats. The level of oxidative stress (MDA, SOD, and GSH) was also found to be lowered in IR rats, together with a reduction in the production of pro-inflammatory cytokines (IL-1b, IL-6, IL-17, and TNF-a). The anti-inflammatory action of PER on IR rats is believed to be linked with the reduction of TNF-a, NF-kB, and TLR4 in both RT-qPCR and western blot analysis. Our research showed that perakine can potentially alleviate cardiac ischemia-reperfusion injury in rats by blocking the TLR4/NF-kB signaling cascade.