Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study)

Abstract

BackgroundArglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PurposeArglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. Study designThis study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 μg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. MethodsOn the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. ResultsArglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. ConclusionArglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.