Open AccessKinetics of the inhibition of renin and angiotensin I-converting enzyme by cod (Gadus morhua) protein hydrolysates and their antihypertensive effects in spontaneously hypertensive rats
Author(s) -
Abraham T. Girgih,
Ifeanyi D. Nwachukwu,
Fida Hasan,
Tayo Nathaniel Fagbemi,
Tom Gill,
Rotimi E. Aluko
Publication year - 2015
Publication title -
food and nutrition research/food and nutrition research. supplement
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 37
eISSN - 1654-6628
pISSN - 1654-661X
DOI - 10.3402/fnr.v59.29788
Subject(s) - gadus , pepsin , hydrolysate , renin–angiotensin system , chemistry , proteolysis , trypsin , enzyme , pharmacology , angiotensin converting enzyme , in vitro , biochemistry , peptide , endocrinology , blood pressure , hydrolysis , medicine , biology , fishery , fish <actinopterygii>
Background Cod muscle has a balanced protein profile that contains potentially bioactive amino acid sequences. However, there is limited information on release of these peptides from the parent proteins and their ability to modulate mammalian blood pressure. Objective The aim of this study was to generate cod antihypertensive peptides with potent in vitro inhibitory effects against angiotensin-converting enzyme (ACE) and renin. The most active peptides were then tested for systolic blood pressure (SBP)-reducing ability in spontaneously hypertensive rats (SHRs). Design Cod protein hydrolysate (CPH) was produced by subjecting the muscle proteins to proteolysis first by pepsin and followed by trypsin+chymotrypsin combination. In order to enhance peptide activity, the CPH was subjected to reverse-phase (RP)-HPLC separation to yield four fractions (CF1, CF2, CF3, and CF4). The CPH and RP-HPLC fractions were each tested at 1 mg/mL for ability to inhibit in vitro ACE and renin activities. CPH and the most active RP-HPLC fraction (CF3) were then used for enzyme inhibition kinetics assays followed by oral administration (200 and 30 mg/kg body weight for CPH and CF3, respectively) to SHRs and SBP measurements within 24 h. Results The CPH, CF3, and CF4 had similar ACE-inhibitory activities of 84, 85, and 87%, which were significantly ( p <0.05) higher than the values for CF1 (69%) and CF2 (79%). Conversely, the CF3 had the highest (63%) renin-inhibitory activity ( p <0.05) when compared to CPH (43%), CF1 (15%), and CF4 (44%). CPH and CF3 exhibited uncompetitive mode of ACE inhibition, whereas renin inhibition was non-competitive. Even at a 6.7-fold lower dosage, the CF3 significantly ( p <0.05) reduced SBP (maximum −40.0 mmHg) better than CPH (maximum −19.1 mmHg). Conclusions RP-HPLC fractionation led to enhanced antihypertensive effects of cod peptides, which may be due to a stronger renin-inhibitory activity.