In silico and in vivo experiment of soymilk peptide (tetrapeptide - FFYY) for the treatment of hypertension.

Enzyme-Treated Soymilk (ETS) was produced from Commercial Soymilk (CSM) with the treatment of proteinase PROTIN SD-NY10 (Bacillus amyloliquefaciens). Previously, we have isolated novel peptides from ETS but data related to isolated-peptides are scant. In this study, bio-informatics and in vivo analysis of isolated-peptides showed strong binding affinity to the active site of the Angiotensin Converting Enzyme (ACE). Among four peptides, tetrapeptide Phe-Phe-Tyr-Tyr (FFYY) showed strong binding affinity and inhibitory activity to the ACE-enzyme (binding affinity -9.5 Kcal/mol and inhibitory concentration of 1.9 µM respectively) as well as showed less toxicity compared to other peptides. The animal experiment revealed that single oral dose of FFYY (80 µg/kg body weight/day) effectively ameliorates the systolic, diastolic and mean blood pressure in the spontaneously hypertensive rat (SHR) model. Chronic oral administration of FFYY (80 µg/kg body weight/day for 3 weeks) reduced the systolic blood pressure elevation and ACE activity without any adverse side effects on the physiological and biological parameters of SHR. In conclusion, both in silico and in vivo experiments of soymilk-isolated FFYY peptide showed a promising option as a potential alternative for hypertension treatment without adverse side effects on SHR.

Novel angiotensin I-converting enzyme inhibitory peptides derived from soya milk.

Inhibitors of angiotensin I-converting enzyme (ACE) are useful in treating hypertension, and many have been derived from food products, including soybeans. Using the industrial protease PROTIN SD-NY10, we developed a processed soya milk (PSM) with enhanced ACE inhibitory activity. The ACE inhibitory activity of PSM (IC(50)=0.26 µg/ml) was greater than that of regular soya milk (IC(50)=8.75 µg/ml). Eight novel ACE inhibitory peptides were purified from PSM by reversed-phase chromatography: FFYY (IC(50),1.9 µM), WHP (4.8 µM), FVP (10.1 µM), LHPGDAQR (10.3 µM), IAV (27.0 µM), VNP (32.5 µM), LEPP (100.1 µM), and WNPR (880.0 µM). The IC(50) values of these peptides are comparable to those reported for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc. Due to the relatively low IC(50) values of several peptides identified in this study, they may serve as ideal base components of food supplements for patients with hypertension.