Antioxidative Effects and Mechanisms of Antihypertensive Potential of Croton gratissimus Burch and Schrankia leptocarpa DC in Rats

Abstract

Introduction: Hypertension is currently recognized as a global public health problem because of its frequency and the associated risks of cardiovascular and renal disease. In this view, medicinal plants such as Croton gratissimus Burch (Crt) and Schrankia leptocarpa DC (Sch) are known to have many and various metabolites possessing potential for the prevention and treatment of several diseases. Methods: The present study was to evaluate the effects of ethanolic extracts of Croton gratissimus Burch and Schrankia leptocarpa DC to assess their antioxidant activity and efficacy in the treatment of L-NAME induced hypertension in Wistar albino rats, heart rate, waves and to elucidate the mechanism of action of the observed effects. Total phenolic content was determined by using the Folin-Ciocalteu method while total flavonoids and condensed tannins were estimated using standard procedures. The antioxidant capacities in the forms of DPPH (2,2-Diphenyl-1-Picrylhydrazyl) and FRAP (Ferric Reducing Antioxidant Power) were evaluated by spectrophotometric methods. Results: The results showed that total phenolic, flavonoids and condensed tannins values were higher in Schrankia leptocarpa DC ethanolic extracts: 40.60 mg equivalent of Gallic acid/g of dry plant, 30.67 mg equivalent of rutin/g of dry plant, 17.50 ± 0.45 mg equivalent of catechin/g of dry Plant. IC50 value of Croton gratissimus Burch extract was 0.3638 mg/ml and Schrankia leptocarpa DC extract was 0.1215 mg/ml as opposed to that of ascorbic acid 0.040 mg/ml. The strongest ferric reducing ability was found in ethanol extract of Schrankia leptocarpa DC (1000 μmol AAE g-1) followed by ethanol extract of Croton gratissimus Burch (800 μmol AAE g-1). Treatment with L-NAME alone resulted in a progressive increase on mean arterial pressure. This increase was significant as early as the first week, as the mean arterial pressure increased from 121 ± 3 mmHg to 140 ± 4 mmHg (p<0.05). After four weeks of treatment, the mean arterial pressure reached a value of 190 ± 2 mmHg, whereas the group receiving L-NAME and Croton gratissimus Burch and Schrankia leptocarpa DC developed a blood pressure of: 170 ± 3 mmHg and 150 ± 4 mmHg only. These results show an antihypertensive effect of these extracts. Moreover, the study of the effect on heart rate of Croton gratissimus Burch and Schrankia leptocarpa DC on the isolated and perfused rat heart model showed a negative inotropic effect which could explain in part the antihypertensive effect found. In summary, Croton gratissimus Burch and Schrankia leptocarpa DC (20 mg/kg) oppose the adrenaline-induced rise in mean arterial pressure throughout the experiment. This opposition to this elevation is more pronounced with Schrankia leptocarpa DC extract. These results suggest that the ethanolic extracts of Croton gratissimus Burch and Schrankia leptocarpa DC has some hypotensive effects via the muscarinic receptors.Lipid profile groups treated with Croton gratissimus Burch and Schrankia leptocarpa DC extracts significantly (p<0.005) decreased. This study shows that these two plants have a hypoglycemic and hypolipidemic effects. We observed significant increases compared to the negative controls in total protein (p<0.005). For serum Na+ concentration in rats, all extracts showed highly significant decreases (p<0.005) when compared with control. For chloride ions, a significant decrease (p<0.005) was found compared with control for the 500 mg/kg dose of Schrankia leptocarpa DC. However, no significant increase was obtained for potassium. Conclusion: The present study suggests that ethanolic extracts of Croton gratissimus Burch and Schrankia leptocarpa have a hypotensive effect mediated by muscarinic receptors. This effect may justify the use of this plant in the treatment of hypertension in traditional medicine.