Therapeutic potential of Olea europaea leaf extract in preventing isoproterenol-induced myocardial injury: integrated biochemical, LC-MS profiling, and molecular docking analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Mediterranean traditional medicine, Olea europaea leaves are largely used to manage hypertension, a significant risk factor for cardiovascular diseases (CVDs), which remain among the leading causes of death worldwide. However, scientific data supporting its effect on myocardial injury are still limited and need further research.

AIM OF THE STUDY: This study assessed the cardioprotective effects of the ethanolic extract of O. europaea leaves (OELE) in a rat model of isoproterenol (ISO)-induced myocardial infarction (MI).

MATERIALS AND METHODS: Wistar rats were pretreated orally with OELE (5 and 10 mg/kg b.w.) or aspirin (10 mg/kg b.w.) for 30 days, followed by ISO injections (85 mg/kg b.w.) on days 29 and 30 to induce MI. The study examined cardiac damage through the use of apoptotic, fibrotic, and oxidative stress markers, along with biochemical tests, histological analysis, and infarct assessment. Additionally, liquid chromatography-mass spectrometry (LC-MS) was used to profile phenolic compounds, while molecular docking techniques were employed to predict and examine their potential interactions with biological targets.

RESULTS: LC-MS/MS analysis identified fifteen bioactive compounds in OELE, including naringenin and luteolin. OELE pretreatment significantly reduced key biomarkers of cardiac injury (aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH), fibrinogen, and troponin-I). It also improved plasma electrolyte balance (Na+, K+, and Ca2+) and positively modulated lipid profiles by lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Antioxidant defenses were enhanced, with decreased lipid peroxidation and increased activities of superoxide dismutase (SOD) and catalase (CAT). The histopathological analysis showed preserved myocardial architecture and reduced inflammatory infiltration. 2,3,5-triphenyltetrazolium chloride (TTC) staining confirmed a significant reduction in infarct size. Molecular docking simulations demonstrated strong binding affinity between OELE bioactive compounds and Protein disulfide isomerase (PDI) and Angiotensin-Converting Enzyme (ACE), suggesting their possible contribution to the observed anti-thrombotic, anti-coagulant, and cardioprotective properties of OELE.

CONCLUSIONS: These findings highlight OELE as a promising natural agent for preventing oxidative cardiac damage, with potential uses in developing nutraceuticals and pharmaceuticals.