Abstract
Introduction: Myocardial infarction (MI) is a major cause of death and illness. Gut dysbiosis and NLR family pyrin domain containing 3 (NLRP3) inflammasome worsen post-MI inflammation and metabolic issues. Esculetin, an anti-inflammatory antioxidant, may help by modulating NLRP3 and restoring metabolic balance.
Objectives: This study aims to investigate the therapeutic effect of esculetin on MI-induced gut dysbiosis via NLRP3 inflammasome and inflammatory/metabolic markers in rats.
Materials and Methods: In this experimental study, thirty male Wistar albino rats were randomized into five groups (n=6) for a study period of 21 days. MI was induced in all but the control group by subcutaneous injection of isoproterenol (100 mg/kg) on two consecutive days. From day three to day 21, three treatment groups received daily oral doses of esculetin at 20, 40, or 60 mg/kg, while control and MI-only groups received standard chow and water or isoproterenol alone, respectively. On day 22, rats were anesthetized, and blood was collected for serum biomarker analysis, including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and interleukin-1 beta (IL-1β), while intestinal tissues were processed for NLRP3 gene expression analysis. Biomarker parameters and NLRP3 gene expression were compared across the five groups.
Results: Isoproterenol elevated TMAO and NLRP3 in rats. Esculetin normalized TMAO at all doses, with no dose-related differences. Esculetin 20 mg/kg normalized NLRP3, with higher doses partially effective. Isoproterenol increased IL-1β, dose-dependently reduced by esculetin, without significant dose-group differences. SCFA analysis showed healthy controls differed from all treatments. Isoproterenol animals matched low-dose esculetin only, with esculetin showing dose-dependent SCFA effects between low and higher doses, which were similar.
Conclusion: Esculetin (20 mg/kg) showed anti-inflammatory and metabolic benefits in isoproterenol-induced conditions, normalizing NLRP3 and TMAO similar to controls and significantly reducing IL-1β. Lower esculetin doses appear therapeutically effective for inflammation and metabolic dysregulation, and no need for higher doses.