LC-MS profile and in vivo oral acute toxicity, antihypertensive and vascular endothelium protective effects of phenolic compounds of the ethyl acetate fraction of leafy stems of Flemingia faginea Guill. & Perr. in L-NAME induced hypertensive mice

Abstract

The present study aimed at evaluating in vivo the antihypertensive and vascular endothelium protection effects of the ethyl acetate fraction of the leafy stem of Flemingia. faginea (EAF) in hypertensive mice with Lῳ- Nitro Arginine Methyl Ester (L-NAME). Methods: Six (06) groups (n = 7) of mice were formed for the study, which lasted five weeks. Groups I, II, and III were administered parenterally with L-NAME (80 mg/kg), NaCl 0.9 % (0.5 mL/kg), and EAF (24 mg/kg) for four weeks, respectively. Mice in groups IV, V, VI, and VII received only L-NAME (80 mg/kg) for two weeks and then received L-NAME plus treatment respectively, captopril 5 mg/kg, 6; 12, and 24 mg/kg for the following two weeks. The acute oral toxicity and phytochemical analysis of EAF were carried out. Results: Daily administration of the L-NAME resulted in a significant increase in BP characterized by SBP= 164.32 ± 6.40 mmHg and DBP= 91.00 ± 0.83 mmHg for all groups concerned on day 21 (p < 0.001). A statistically significant decrease in BP was observed from day seven for the hypertensive mice groups treated with 6; 12, and 24 mg/kg of EAF, and Captopril (5 mg/kg) versus L-NAME (80 mg/kg) only. Aortic rings of mice in the L-NAME+EAF 24 mg/kg group (E_max=69.21±2.70 % and EC₅₀=5.08 ± 0.37 ×10⁻⁷ M) showed more effective and potent nitric oxide (NO) endothelium-dependent vasorelaxation than the reference group L-NAME+Captopril 5 mg/kg (E_max=49.64±7.67 %). The 50 % lethal dose of EAF was estimated to be 5000 mg/kg. Phytochemical analysis identified mainly gallic acid glucoside, myricetin rutinoside, quercetin rutinoside, kaempferol rutinoside, and quercetin rhamnoside. Conclusion: These results suggest that EAF, a potential drug candidate, could be used preventively and curatively to manage hypertension.