Modulatory Effect of Guinep (Melicoccus bijugatus Jacq) Fruit Pulp Extract on Isoproterenol-Induced Myocardial Damage in Rats. Identification of Major Metabolites Using High Resolution UHPLC Q-Orbitrap Mass Spectrometry.

Chukwuemeka Nwokocha,Magdalene Nwokocha,Adrian Paredes,Mario Simirgiotis,Fredi Cifuentes,Rory Thompson,Javier Palacios,Jorge Bórquez,Isheba Warren,Sharon Harrison,Astrid Lavado

doi:10.3390/molecules24020235

Abstract

Guinep is traditionally used in the management of cardiovascular ailments. This study aims to evaluate its medicinal constituents and effects in the management of myocardial injury in an experimental isoproterenol (ISO) rat model. Sprague-Dawley rats were randomly assigned to four groups: Group 1 was the control group; Group 2 received M. bijugatus extract (100 mg/Kg; MB) for six weeks; Group 3 was given ISO (85 mg/Kg) i.p. twice during a 24-hour period; and Group 4 was given ISO (85 mg/Kg) i.p. and MB extract (100 mg/Kg) for six weeks. The MB was administered orally by gavage, daily. The blood pressure of conscious animals was measured, while ECG was performed under anesthesia. Blood and serum were collected for biochemical and hematological analysis. The ISO group treated with MB showed a significant decrease (p < 0.001) in (SBP), diastolic (DBP), mean arterial (MAP) and heart rate (HR) compared to the ISO only group. Conversely, MB treated rats that were not induced with ISO displayed a significant decreases (p < 0.001) in SBP, DBP, MAP, and HR. ISO significantly elevated the ST segment (p < 0.001) and shortened the QTc interval (p < 0.05), which were recovered after treatment with 100 mg/Kg of MB. In addition, the results showed a significant decrease (p < 0.001) in the heart to body weight ratio of the ISO group treated with MB compared to the ISO only group. Furthermore, the extract normalized the hematological values depressed by the ISO while significantly elevating the platelet count. UHPLC high-resolution orbitrap mass spectrometry analysis results revealed the presence of several antioxidants like vitamin C and related compounds, phenolic acids, flavonoid, fatty acids (oxylipins), and terpene derivatives. The results of this study indicated that Melicoccus bijugatus did display some cardio-protective effects in relation to myocardial injury.

Highlights

Cardiovascular disease (CVD) like acute myocardial infarction (AMI) is one of the leading causes of death; causing prolonged ischemia of the heart muscle resulting in tissue death or infarction in the myocardium [1]
There was a significant decrease in the MAP, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the ISO group treated with MB compared to the ISO only group (p < 0.001)
There was a significant decrease (p < 0.001) in the heart rate (HR) of the ISO plus MB treatment group when compared to the ISO only treatment group (Figure 1, Table 1)

Summary

Introduction

Cardiovascular disease (CVD) like acute myocardial infarction (AMI) is one of the leading causes of death; causing prolonged ischemia of the heart muscle resulting in tissue death or infarction in the myocardium [1]. This results in edema, a reduction in cardiac output, abnormalities in cardiac rhythm and transmission blocks that can further impair cardiac function. Its proposed mechanism of action is through the auto-oxidation and production of free cytotoxic radicals [5], as well as hyper-stimulation of beta adrenoceptors [6] These actions lead to the peroxidation of the cellular membrane, a change in membrane permeability and possible derangement of calcium ion pathway signaling, hypertrophy and myocardial injury [7,8]. Cardiac output may increase because of the positive inotropic and chronotropic effects of the drug, due to a decrease in peripheral vascular resistance

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