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

• Published in: Journal of dairy science Vol. 103; no. 3; pp. 2053 - 2064
• Main Authors: Hussein, Fatima A., Chay, Shyan Yea, Ghanisma, Siti Balqis M., Zarei, Mohammad, Auwal, Shehu M., Hamid, Azizah A., Ibadullah, Wan Zunairah Wan, Saari, Nazamid
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2020
• Subjects: angiotensin-converting enzyme (ACE) inhibition; bioactive peptide; hydrolysis; rat study; whey protein concentrate; rat study; bioactive peptide; hydrolysis; whey protein concentrate; angiotensin-converting enzyme (ACE) inhibition
• ISSN: 0022-0302; 1525-3198
• DOI: 10.3168/jds.2019-17462

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.