Cardio-renal protection and mechanisms of the antihypertensive activity of Alcalase-derived moth bean hydrolysate in DOCA-salt induced hypertensive Wistar rats

Hypertension remains a major global health concern, often leading to severe cardiovascular and renal complications. In this study, we investigated the antihypertensive and cardiorenal protective effects of AF4, a bioactive Alcalase derived peptide fraction (< 1 kDa) derived from moth bean protein hydrolysate, in a DOCA-salt hypertensive rat model. AF4 administration significantly reduced systolic blood pressure in a dose-dependent manner, with the minimum effective dose (75 mg/kg body weight/day) selected for further mechanistic evaluation. Treatment with AF4 improved various physiological parameters, including heart rate, cardio-myocytes conduction, electrocardiogram (ECG) abnormalities, and kidney function markers. Biochemical analyses revealed that AF4 act as ACE inhibitor, led to reduction of angiotensin II plasma levels, and subsequently endothelin-1, and vasopressin, while enhancing nitric oxide (NO) bioavailability. The antioxidant capacity of AF4, both direct and enzyme-mediated, reduced oxidative stress and inflammation by lowering ROS, TNF-α, and IL-6 levels, thereby preventing endothelial dysfunction and vascular damage. Histopathological analysis of cardiac and renal tissues demonstrated that AF4 mitigated fibrosis, myocardial infarction, and renal sclerosis, further confirming its protective effects. Overall, AF4 displayed significant antihypertensive potential through its multifaceted actions on RAAS modulation, oxidative stress reduction, and inflammation control, providing a promising candidate for the management of hypertension and associated organ damage.