THERAPEUTIC EFFICACY AND MECHANISMS OF ACTION OF PERSEAAMERICANA EXTRACTS ON HYPERTENSION AND CARDIO-RENAL OXIDATIVE STRESS INDUCED BY NΩ-NITRO-L-ARGININE METHYL ESTER

Abstract

Cardiovascular diseases are the leading causes of death worldwide with hypertension being the major risk factor. The adverse effects of synthetic medications have made the search for safer and effective herbal therapies imperative. Persea americana(PA) is a medicinal plant with diverse health benefits. There is dearth of information on its safety and efficacy in the management of hypertension.The safety and ameliorative effects of PA extractson NΩ-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal oxidative stress were investigated.

In vitro anti-inflammatory and anti-hypertensive assays were carried out separately on methanol PA leaf (PALE), stem bark (PABE), and root (PARE) extracts (UIH22531). Standard in vitro protocols were adopted using gallic acid, indomethacin and captopril, respectively, as standard drugs. Half maximum Inhibition Concentrations (IC50) were calculated using IC50 calibration curve. Male Wistar rats (7 groups, n=4/group) received distilled water (control) and variable doses of PA extracts (1000, 2000, 4000, 5000, 6000 and 7500 mg/kg) once to determine the Lethal Dose (LD50). Antihypertensive effect of PA was evaluated using 120 male rats randomly allotted to 12 groups (n=10). These received distilled water, L-NAME (40 mg/kg), L-NAME+ PALE (100, 200, 400 mg/kg), L-NAME + PABE (100, 200, 400 mg/kg) and L-NAME + PARE (100, 200, 400 mg/kg) and L-NAME + lisinopril (0.28 mg/kg). Blood pressure (BP) measurement and electrocardiogram were performed. Immunoreactivity of NF-ĸB, marker of oxidative stress: Malondialdehyde (MDA) and antioxidants: Superoxide dismutase(SOD) and Reduced Glutathione (GSH) were evaluated in the cardiac and renal tissues. Data were analysed using descriptive statistics and ANOVA at α0.05.

Persea americana extracts demonstrated anti-inflammatory activities with IC50 of the PALE (100.86±2.77), PABE (101.54±9.01) and PARE (101.74±13.10) comparable to Indomethacin (115.09±1.62). The extracts had anti-hypertensive activities with IC50 of 135.99±10.06, 29.64±0.92, 48.61±6.56, respectively, for PALE, PABE and PARE comparable to captopril (IC50 = 41.86±2.10). LD50 (mg/kg) for PALE, PABE and PARE were 3162.30, 3463.90 and 5477.20, respectively. Persea americana extracts significantly reduced systolic BP (mmHg) from 224.33±11.89 to110±31.87 (PALE-200), 113.67±9.49 (PABE-200) and 111.33±17.84 (PARE-200). A significant increase in QT interval (ms) in hypertensive rats (106.00±1.00) compared to the control (45.33±26.03) was reduced to 62.00±11.53 (PALE-100), 67.67±11.66 (PABE-200) and 62.67±1.53 (PARE-100) better than lisinopril (86.00±10.64). Treatment of hypertensive rats with PA extracts caused significant reduction in NF-ĸB expression, cardiac MDA (µmol/mgprotein) from 0.87±0.25 to 0.44±0.08 (PALE-200), 0.55±0.14 (PABE-200) and 0.33±0.22 (PARE-200) as well as renal MDA from 1.11±0.04 to 0.41±0.14 (PALE-200), 0.60±0.19 (PABE-200) and 0.74±0.18 (PARE-200). Cardiac SOD (units/mgprotein) increased from 1.19±0.05 to24.03±5.74 (PALE-200), 15.12±6.07 (PABE-200) and 11.27±1.03 (PARE-200) and renal SOD from 5.27±4.13 to 7.59±0.99 (PALE-200), 16.19±0.85 (PABE-200) and 9.59±1.05 (PARE-200). Cardiac GSH (µmol/mgprotein) increased from 51.82±13.20 to 88.37±1.55 (PALE-200), 73.77±11.53 (PABE-200) and 68.86±7.99 (PARE-200) comparable to lisinopril (68.74±3.68).

Persea americana is safe and effective at 200 mg/kg, ameliorating hypertension induced cardio-renal damages through free radical scavenging and anti-inflammatory activities. Thus, the plant is recommendedfor the management of hypertension and cardio-renal dysfunction.