Identification and Effects of Skim Milk-Derived Bioactive Antihypertensive Peptides

Fatah B Ahtesh,Vasso Apostolopoulos,Marijan Bosevski,Lily Stojanovska,Jack Feehan,Osaana Donkor,Vijay Mishra,Michael Mathai

doi:10.3390/biologics2010001

Fatah B Ahtesh, Vasso Apostolopoulos + Show 6 more

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https://doi.org/10.3390/biologics2010001

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Abstract

Bioactive peptides are generated during milk fermentation or enzymatic hydrolysis. Lactobacillus (L) helveticus is commonly used to produce some types of fermented milk products. Fermented milk derived bioactive peptides are known to be beneficial in human health. Anti-hypertensive peptides play a dual role in the regulation of hypertension through the production of the vasoconstrictor angiotensin II and its inactivation of the vasodilator bradykinin. MALDI MS/MS, nano-LC/MS/MS and RP-HPLC were used to isolate peptides showing angiotensin converting enzyme inhibition (ACE-I) from 12% fermented skim milk using a combination of L. helveticus and Flavourzyme®. The fermentation procedure facilitated the identification of 133 anti-hypertensive peptides and 75% short chain amino acids, and the three with the highest ACE-I activity reduced blood pressure in a rat model of hypertension. The freeze- dried extract was supplemented in rodent chow. In this study 14-week-old male spontaneously hypertensive rats were fed for 10 weeks with the identified peptides added to chow and compared to controls supplemented with skim milk powder. Blood pressure (BP) decreased significantly (p < 0.05) from 6 to 10 weeks of FS groups (120/65 mmHg) compared with the NFS control groups, where the BP increased significantly (220/150 mmHg) (p < 0.05). The F6 fraction provided bioactive peptides with stronger antihypertensive properties than other fractions. Skim milk fermented by L. helveticus and Flavourzyme® generates several bioactive peptides which have a blood pressure lowering effect in hypertensive disease.

Highlights

Introduction iationsFermented dairy products are known to provide a large volume of nutrients and bio-functional peptides which are linked to improved health benefits [1,2,3]
The micro-fluidic Loa-C method provides a unique approach to the real-time separation of major milk proteins as well as giving information on size, concentration and purity of proteins in a single assay [30]
The migration pattern and profile shows a number of peaks ranging from 5–240 kDa in fermented milk. This indicates the products of the casein and other milk protein hydrolysates with a range of molecular weights of the resulting peptides

Summary

Introduction

Introduction iationsFermented dairy products are known to provide a large volume of nutrients and bio-functional peptides which are linked to improved health benefits [1,2,3]. A quarter of the world’s adult population suffer from hypertension [4], of which a third are from western countries [5]. Recent studies have estimated that 1.13 billion people worldwide have hypertension, with two-thirds of those living in low- and middle-income countries. In 2015, one in four men and one in five women had hypertension [6]. Hypertension increases incidence and severity of impaired kidney function, cardiovascular disease, peripheral artery disease, heart failure and stroke [4]. Angiotensin converting enzyme inhibitory (ACE-I) peptides from the enzymatic hydrolysis of milk proteins are able to reduce the blood pressure in rat models of hypertension [7,8,9].

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