Cucumis sativus L., widely cultivated as an edible vegetable. Its seeds are well reputed for cardiovascular preventive properties. However, the mechanisms underlying for cardiovascular protection of C. sativus are still unidentified. Therefore, this study utilized a metabolomics approach to investigate putative mechanisms of C. sativus seeds in myocardial infarction (MI) and in vitro models of vasoconstriction, atrium, and invasive blood pressure measurement. Results showed that Cu. EtOH extract showed a vasorelaxant response with potent hypotensive effect in normotensive rats and L-NAME induced hypertension. Cu. EtOH caused a negative inotropic and positive chronotropic effect on the atrium. Cu. EtOH protected the animals from ISO-induced myocardial infarction (MI) interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, and biochemical assays. The metabolomics data suggested that Cu. EtOH mainly affected amino acid metabolism, BCAA degradation, ketone bodies degradation, and oxidative stress. Our study showed that Cu. EtOH suppressed inflammation with a strong...

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