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Anti-Hypertensive Peptides Derived from Caseins: Mechanism of Physiological Action, Production Bioprocesses, and Challenges for Food Applications

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Abstract

This review is focused on the state-of-art of peptides with inhibitory activity towards angiotensin I-converting enzyme (ACE) — thus, with anti-hypertensive potential — derived from enzymatic hydrolysis of caseins. Firstly, molecular characteristics of caseins relevant to a better understanding of this subject were concisely commented. Next, a brief description of the pathophysiology of hypertension was explained, focusing on the ACE role in regulation of blood pressure in human body. Then, casein-derived peptides with ACE inhibitory capacity were specifically addressed. The main in vitro and in vivo bioassays often reported in literature to assess the anti-hypertensive potential of peptides were presented, illustrated with recently published studies, and discussed in terms of advantages and limitations of both approaches. Characteristics related to amino acid composition and sequence of peptides with high ACE-inhibitory potential were also commented. Process parameters of enzymatic hydrolysis (types and origins of casein substrates, types of enzymes, pH, temperature, and times of reactions) were discussed. Patents dealing with casein-derived anti-hypertensive peptides were examined not only in terms of amino acid sequences, but also regarding their novelty claims in hydrolysis process parameters. Finally, some trends, challenges, and opportunities inferred from this literature analysis were commented, emphasizing the importance of this research topic in food products development.

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Abbreviations

AC:

Affinity chromatography

ACE:

Angiotensin converting enzyme

AHTPDB:

Anti-hypertensive peptides data base

Ang I:

Angiotensin I

Ang II:

Angiotensin II

ESI:

Electrospray ionization

E:S:

Enzyme-to-substrate ratio

GMP:

Glycomacropeptide

GRAS:

Generally recognized as safe

HHL:

Hippuryl-l-histidyl-l-leucine

HILIC:

Hydrophilic interaction liquid chromatography

HPLC:

High performance liquid chromatography

HT:

Hypertension

IEC:

Ion-exchange chromatography

IEF:

Isoelectric focusing

KKS:

Kallikrein-kinin System

LC:

Liquid chromatography

MALDI:

Matrix-assisted laser desorption/ionization

MRM:

Multiple reaction monitoring

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

NO:

Nitric oxide

PGI2 :

Prostaglandins 2

QIT:

Quadrupole ion trap

RAS:

Renin-angiotensin system

RP-HPLC:

Reversed phase-HPLC

SEC:

Size-exclusion chromatography

SHR:

Spontaneously hypertensive rat

TOF:

Time-of-flight

UF:

Ultrafiltration

UHPLC:

Ultra high pressure liquid chromatography

αs1-CN:

AlphaS1-casein

αs2-CN:

AlphaS2-casein

β-CN:

Beta-casein

κ-CN:

Kappa-casein

λ :

Wavelength (nm)

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Funding

The authors acknowledge the Brazilian funding agencies CNPq and FAPEMIG, for the financial support. Ms. M.R. Oliveira and Ms. T.J. Silva also acknowledge the Brazilian funding agency CNPq, for their scholarships.

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Authors and Affiliations

  1. Departamento de Tecnologia de Alimentos (DTA), Universidade Federal de Viçosa (UFV), Campus Universitário, s/n, Viçosa, MG, 36570-900, Brazil

    Mara Rose de Oliveira, Thaís Jordânia Silva, Monique Renon Eller, Jane Sélia dos Reis Coimbra & Eduardo Basílio de Oliveira

  2. Núcleo de Análise de Biomoléculas (NuBioMol), Universidade Federal de Viçosa (UFV), Campus Universitário, Viçosa, MG, 36570-900, Brazil

    Edvaldo Barros

  3. Departamento de Bioquímica e Biologia Molecular (DBB), Universidade Federal de Viçosa (UFV), Campus Universitário, s/n, Viçosa, MG, 36570-900, Brazil

    Valéria Monteze Guimarães & Maria Cristina Baracat-Pereira

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  1. Mara Rose de Oliveira
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  2. Thaís Jordânia Silva
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  3. Edvaldo Barros
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  7. Jane Sélia dos Reis Coimbra
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  8. Eduardo Basílio de Oliveira
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Correspondence to Eduardo Basílio de Oliveira.

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Mara Rose de Oliveira and Thaís Jordânia Silva contributed equally to this work.

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de Oliveira, M.R., Silva, T.J., Barros, E. et al. Anti-Hypertensive Peptides Derived from Caseins: Mechanism of Physiological Action, Production Bioprocesses, and Challenges for Food Applications. Appl Biochem Biotechnol 185, 884–908 (2018). https://doi.org/10.1007/s12010-018-2692-8

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