Toxicity study and blood pressure–lowering efficacy of whey protein concentrate hydrolysate in rat models, plus peptide characterization

• Published in: Journal of Dairy Science
• Main Author: Hussein F.A.; Chay S.Y.; Ghanisma S.B.M.; Zarei M.; Auwal S.M.; Hamid A.A.; Ibadullah W.Z.W.; Saari N.
• Format: Article
• Language: English
• Published: Elsevier Inc. 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076828433&doi=10.3168%2fjds.2019-17462&partnerID=40&md5=5d1a55542476b6112d08e31c5647c573

We evaluated the acute (single-dose) and subacute (repeated-dose) oral toxicity of alcalase-hydrolyzed whey protein concentrate. Our acute study revealed no death or treatment-related complications, and the median lethal dose of whey protein concentrate hydrolysate was >2,500 mg/kg. In the subacute study, when the hydrolysate was fed at 3 different concentrations (200, 400, and 800 mg/kg), no groups showed toxicity changes compared with controls. Then, whey protein concentrate hydrolysate was orally administered to spontaneously hypertensive rats. Results revealed significant reductions in blood pressure in a dose-dependent manner, and dosing at 400 mg/kg led to significant blood pressure reduction (−47.8 mm Hg) compared with controls (blood pressure maintained) and the findings of previous work (−21 mm Hg). Eight peptides—RHPEYAVSVLLR, GGAPPAGRL, GPPLPRL, ELKPTPEGDL, VLSELPEP, DAQSAPLRVY, RDMPIQAF, and LEQVLPRD—were sequentially identified and characterized. Of the peptides, VLSELPEP and LEQVLPRD showed the most prominent in vitro angiotensin-I converting enzyme inhibition with half-maximal inhibitory concentrations of 0.049 and 0.043 mM, respectively. These findings establish strong evidence for the in vitro and in vivo potential of whey protein concentrate hydrolysate to act as a safe, natural functional food ingredient that exerts antihypertensive activity. © 2020 American Dairy Science Association