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. Results of the study suggest that PER significantly lowered the infarct size and
volume, and 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 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.