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In the management of hypertension (a cardiovascular disease and the leading metabolic risk factor in noncommunicable diseases) with herbal medicines, efficacy and safety are of uttermost concern. This study sought to establish hypotensive, antihypertensive, drug interaction, and safety for use of the aqueous leaf extracts of  Annona muricata  (AME),  Persea americana  (PAE), or their combination products (CAPE).  Methodology . Systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure (MAP), and heart rate (HR) were measured in normotensive Sprague-Dawley rats treated with 50–150 mg/kg of AME, PAE, or CAPE to establish a hypotensive effect. “Combination index” was calculated to establish interaction between AME and PAE. The antihypertensive effect of CAPE was established by measuring SBP, DBP, MAP, and HR in ethanol-sucrose- and epinephrine-induced hypertension. Full blood count, liver and kidney function tests, and urinalysis were determined in ethanol/sucrose-induced hypertension to establish safety for use.Results   AME, PAE, and CAPE significantly ( p  ≤ 0.001) decreased BP in both normotensive and hypertensive animals. Effects of CAPE 1, CAPE 2, and CAPE 3 were synergistic (combination indices of 0.65 ± 0.07, 0.76 ± 0.09, and 0.87 ± 0.07, respectively). There was a significant decrease ( p  ≤ 0.01 − 0.001) in SBP and MAP with 100 mg/kg CAPE 1 and 75 mg/kg CAPE 2 treatment in hypertension as well as with nifedipine ( p  ≤ 0.001) treatment. Epinephrine-induced hypertension in anesthetized cats was significantly and dose-dependently inhibited ( p  < 0.05 − 0.001) by 25–100 mg/ml CAPE 1 and 37.5–75 mg/ml CAPE 2. CAPE administration had no deleterious effect ( p  > 0.05) on full blood count, liver and kidney function, and urine composition in hypertensive rats.Conclusion   The aqueous leaf extracts of  Annona muricata, Persea americana , and their combination products possess antihypertensive properties, with combination products showing synergism and safety with use.

Hypotensive and Antihypertensive Properties and Safety for Use of Annona muricata and Persea americana and Their Combination Products