Aegeline mitigates isoproterenol-induced myocardial infarction: insights from biochemical, histopathological, and in...

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Although considerable advances have been made in its diagnosis and management, the development of safe and effective cardioprotective agents remains an active area of investigation. Natural products continue to attract interest as potential therapeutic candidates because of their diverse pharmacological activities. Aegeline, an alkaloidal amide isolated from Aegle marmelos, has demonstrated antioxidant and anti-inflammatory properties; however, its cardioprotective effects in experimental myocardial injury have not been fully characterized.

The aim of this work was to assess the cardioprotective effects of aegeline in an experimental MI model.

Isoproterenol (ISO) (85 mg/kg, subcutaneouslySC) was employed to trigger acute MI in experimental rats. Aegeline was administered to the rats at doses of 5 and 10 mg (p.o.) on the 29th and 30th day, respectively, followed by ISO (85 mg/kg) (s.c.) on the same days.

Aegeline exhibited cardioprotective properties against ISO-induced damage, as evidenced by the amelioration of altered histopathological features, reduction in myocardial damage, and improvements in antioxidant and oxidative stress markers, inflammatory indicators, and signaling pathways, along with inhibition of apoptotic expression. In addition, aegeline did not affect liver or kidney function. Molecular docking using AutoDock Vina v1.2.6 revealed the strong binding affinity of aegeline for CK-MB (PDB ID: 3B6R), with key hydrophobic, hydrogen-bonding, and salt bridge interactions. Additional targets included LDH (7DBJ), cTnT (1J1D), and cTnI (7SC2), though CK-MB exhibited the most favorable interaction profile. Molecular dynamics simulations supported these findings through principal component analysis, dynamic cross-correlation, free energy landscape mapping, and generalized born surface area (MM-GBSA) binding free energy analysis.

This study demonstrates that aegeline attenuates experimental myocardial injury by reducing oxidative stress, inflammation, and apoptosis. Computational analyses support potential molecular interactions with proteins associated with myocardial injury, while the biochemical and histopathological findings provide primary evidence for its cardioprotective activity.