Peristrophe bicalyculata as a potential antihypertensive drug: Effect on Angiotensin Converting Enzyme (ACE) activity of two kidney one clip hypertensive (2K1C) and diet-induced obese Wistar rats (Rattus norvergicus)

Abdulazeez, A.M
Department of Biochemistry, Faculty of Sciences, Ahmadu Bello University ,Zaria, Kaduna State, Nigeria,

Abstract:

Peristrophe bicalyculata is used in South West Nigeria for the treatment of hypertension and other cardiovascular diseases, with very little documented on its efficacy. Three independent experiments were carried out. The first was to determine the effect of Peristrophe bicalyculata on blood pressure and activity of angiotensin converting enzyme in serum, heart and kidney of rats made hypertensive using the Goldblatt method. A total of forty rats were divided into five groups of eight rats each: control group, hypertensive control, standard group (given enalapril 3.8mg/kg) and extract treated groups (100 and 250 mg/kg). Treatment began four weeks after induction of hypertension, and lasted for two weeks.  Blood pressure was determined before inducing hypertension, and then weekly after the induction. At the end of experiment, animals were euthanized and serum, kidney and heart ACE activity in treated rats were compared with rats in hypertensive control and control groups. The second study was to determine the effect of the plant on diet-induced obese Wistar rats. Forty rats were divided into five groups of eight rats: control group, obese control, standard group (given atorvastatin 70 mg/kg) and extract treated groups (100 and 250 mg/kg). Obesity was induced by feeding rats high fat diet for 8 weeks after which they were treated for 2 weeks. In the third experiment, the inhibitory effect of Peristrophe bicalyculata on ACE was studied. Results showed a significant increase (p < 0.05) in blood pressure, serum and tissue ACE activity of hypertensive rats compared to rats in the control group. These parameters significantly decreased on administration of the extract (250 mg/kg) and the standard drug. In the second experiment, ACE activity was found to increase significantly (p<0.05) in lungs, kidney and heart of obese control rats compared to those in normal control group. The ACE activity in tissues of all rats treatedwith Peristrophe bicalyculata was significantly lower (p<0.05) than those of obese control rats. The inhibition kinetics showed a dose-dependent inhibitory effect on ACE, as it increased the Km of ACE from 0.25mM to 2.5mM for 1% extract and 5mM for 2% extract while the Vmax remained unchanged (0.063nmoles/min/ml). The ki was found to be 1.1mg/ml. In conclusion, this study has established the antihypertensive and hypolipidemic properties of Peristrophe bicalyculata, with blood pressure decreasing from 190 ± 4 mmHg to 130 ± 6 mmHg. Furthermore, we established that the plant competitively inhibited ACE, and that the mode of action of Peristrophe bicalyculata may be through the Renin Angiotensin Aldosterone System (RAAS).