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Isolation and Characterization of Angiotensin Converting Enzyme Inhibitory Peptide from Buffalo Casein

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Abstract

Angiotensin-converting enzyme (ACE) enhances blood pressure by making potential vasoconstrictor, Angiotensin-II from Angiotensin-I. Thus, it is the key target enzyme in cardiovascular disease therapy. Hence, in the present study an attempt has been made for identification and characterization of ACE inhibitory peptide from buffalo milk casein. Buffalo milk casein was isolated and digested with different digestive enzymes (pepsin, trypsin, chymotrypsin and their combination). Pepsin-Trypsin hydrolysates shown highest (72.55 ± 2.23%/50 μg) ACE inhibitory activity, in further ultra-filtration, < 1 kDa fraction shown the highest inhibitory activity among the other fractions. Below 1 kDa filtrate was further fractionated through RP-HPLC, fraction 11 exhibited the highest ACE inhibitory activity. Out of 15 peptides of 11th fraction (LC–MS/MS sequence) VLPVPQK is the novel peptide, which shown significant ACEI activity. Therefore, this study supports the notion that milk is a very good nutraceutical, and the novel peptide sequence can be utilized in commercial peptide synthesis for making functional food preparation.

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References

  • Abubakar A, Saito T, Kitazawa H, Kawai T, Itoh T (1998) Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinse K digestion. J Dairy Sci 81(12):3131–3138

    CAS  PubMed  Google Scholar 

  • Addeo F, Chobert JM, Ribadeau-Dumas B (1977) Fractionation of whole casein on hydroxyl apatide: Application to a study of buffalo κ–casein. J Dairy Res 44:63–68

    CAS  PubMed  Google Scholar 

  • Alhaj OA (2017) Identification of potential ACE-inhibitory peptides from dromedary fermented camel milk. CyTA - J Food 15(2):191–195

    CAS  Google Scholar 

  • Cheung HS, Wang FL, Ondetti MA, Sabo EF, Cushman DW (1980) Binding of peptide substrate and inhibitors of angiotensing converting enzyme. J Biol Chem 255:401–407

    CAS  PubMed  Google Scholar 

  • Church FC, Swaisgood HE, Porter DH, Catignani GL (1983) Spectrophotometric assay using O-phthaldehyde for determination of proteolysis in milk and isolated milk proteins. J Dairy Sci 66:1219–1227

    CAS  Google Scholar 

  • Cushman DW, Cheung HS (1971) Spectrophotometric assay and properties of the angiotensin converting enzyme of rabbit lung. Biochem Pharmacol 20(7):1637–1648

    CAS  PubMed  Google Scholar 

  • Davies DT, Law AJR (1977) An improved method for the quantitative fractionation of casein mixture using ion-exchange chromatography. J Dairy Res 44:213–221

    CAS  Google Scholar 

  • Deepthi K (2004) Comparative studies on casein derived ACE inhibitory and immunomodulatory peptides from cow and buffalo milk. Ph.D Thesis NDRI (Deemed University), Karnal, India

  • Ferreia SH, Bartert DC, Greene LJ (1970) Isolation of bradykinin potentiating peptides from Bothrops iararaca venom. Biochemistry 9:2583–2593

    Google Scholar 

  • FitzGerald RJ, Meisel H (2000) Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme. Br J Nutr 84(Suppl. 1):S33–S37

    CAS  PubMed  Google Scholar 

  • García-Moreno PJ, Espejo-Carpio FJ, Guadix A, Guadix EM (2015) Production and identification of angiotensin I-converting enzyme (ACE) inhibitory peptides from Mediterranean fish discards. J Funct Foods 18:95–105

    Google Scholar 

  • Haque E, Chand R, Kapila S (2009) Biofunctional properties of bioactive peptides of milk origin. Food Reviews International 25(1):28–43

    CAS  Google Scholar 

  • Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T (1996) A placebo-controlled study of the effect of sour milk onblood pressure in hypertensive subjects. Am J Clin Nutr 64(5):767–771

    CAS  PubMed  Google Scholar 

  • Hernández-Ledesma B, Contreras M, Recio I (2011) Antihypertensive peptides: Production, bioavailability and incorporation into foods. Adv Colloid Interface Sci 165:23–35

    PubMed  Google Scholar 

  • Hernandez-Ledesma B, Martin-Alvarez PJ, Pueyo E (2003) Assessment of the spectrophotometric method for determination of angiotensin-converting enzyme activity: Influence of the inhibition type. J Agric Food Chem 51(15):4175–4179

    CAS  PubMed  Google Scholar 

  • Hernandez-Ledesma B, Recio I, Ramos M, Amigo L (2002) Preparation of ovine and caprine β-lactoglobulin hydrolysates with ACE inhibitory activity: influence of the inhibition type. J Agril Food Chem 51:4175–4179

    Google Scholar 

  • Huang GJ, Lu TL, Chiu CS, Chen HJ, Wu CH, Lin YC, Hsieh WT, Liao JC, Sheu MJ, Lin YH (2011) Sweet potato storage root defensing and its tryptic hydrolystes exhibited angiotensin converting enzyme inhibitory activity in vitro. Bot Stud 52:257–264

    CAS  Google Scholar 

  • Ibrahim HR, Ahmed AS, Miyata T (2017) Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk. J Adv Res. https://doi.org/10.1016/j.jare.2016.12.002

  • Jenness R, Holt C (1987) Casein and lactose concentrations in milk of 31 species are negatively correlated. Experimentia 43:1015–1018

    CAS  Google Scholar 

  • Guo J, Astrup A, Lovegrove JA, Gijsbers L, Givens DI, Soedamah-Muthu SS (2017) Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose–response meta-analysis of prospective cohort studies. Eur J Epidemiol 32:269–287

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin K, Zhang L, Han X, Meng Z, Zhang J, Yifan Wu, Cheng D (2018) Quantitative structure-activity relationship modeling coupled with molecular docking analysis in screening of Angiotensin I-converting enzyme inhibitory peptides from Qula Casein hydrolysates obtained by two-enzyme combination hydrolysis. J Agric Food Chem 66(12):3221–3228

    CAS  PubMed  Google Scholar 

  • Korhonen H, Pihlanto A (2006) Bioactive peptides: production and functionality—review. Int Dairy J 16:945–960

    CAS  Google Scholar 

  • Laemmli VK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(15):680–685

    CAS  Google Scholar 

  • Lee SY, Hur SJ (2017) Angiotensin converting enzyme inhibitory and antioxidant activities of enzymatic hydrolysates of Korean Native Cattle (Hanwoo) myofibrillar protein. BioMed Res Int. https://doi.org/10.1155/2017/5274637

    Article  PubMed  PubMed Central  Google Scholar 

  • Li G, Le G, Shi Y, Shrestha S (2004) Angiotensin I–converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects. Nutr Res 24:469–486

    CAS  Google Scholar 

  • Lu Z, Karne S, Kolodecik T, Gorelick FS (2002) Alcohols enhance caerulein-induced zymogen activation in pancreatic acinar cells. Am J Physiol Gasterointest Liver Physiol 282:G501–G507

    CAS  Google Scholar 

  • Mada SB, Reddi S, Kumar N, Kumar R, Kapila S, Kapila R, Trivedi R, Karvande A, Ahmad N (2017) Antioxidative peptide from milk exhibits anti-osteopenic effects through inhibition of oxidative damage and bone-resorbing cytokines in ovariectomized rats. Nutrition 43–44:21–31

    PubMed  Google Scholar 

  • Mada SB, Reddi S, Kumar N, Vij R, Yadav R, Kapila S, Kapila R (2018) Casein-derived antioxidative peptide prevents oxidative stress-induced dysfunction in osteoblast cells. Pharmanutrition 6:169–179

    Google Scholar 

  • Maeno M, Yamamoto N, Takano T (1996) Identification of an antihypertensive peptide from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J Dairy Sci 79(8):1316–1321

    CAS  PubMed  Google Scholar 

  • Mao X, Cheng X, Wang X, Wu S (2011) Free-radical-scavenging and anti-inflammatory effect of yak milk casein before and after enzymatic hydrolysis. Food Chem 126:484–490

    CAS  Google Scholar 

  • Maolin Tu, Wang C, Chen C, Zhang R, Liu H, Weihong Lu, Jiang L, Ming Du (2018) Identification of a novel ACE-inhibitory peptide from casein and evaluation of the inhibitory mechanisms. Food Chem 256:98–104

    Google Scholar 

  • Akif M, Masuyer G, Bingham RJ, Sturrock ED, Elwyn Isaac R, Ravi Acharya K (2012) Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster. FEBS J 279:4525–4534

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mullally MM, Meisel H, FitzGerald RJ (1997) Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins. Int Dairy J 7:299–303

    CAS  Google Scholar 

  • Ondetti MA, Williams NJ, Sabo EF, Plusce J, Weaver ER, Kocy O (1971) Angiotensin converting enzyme inhibitors from the venom of Borthrops jararaca, isolation, elucidation of structure and synthesis. Biochemistry 19(22):4033–4039

    Google Scholar 

  • Pandey M, Kapila R, Kapila S (2018) Evaluation of the osteoprotective potential of whey derived-antioxidative (YVEEL) and angiotensin-converting enzyme inhibitory (YLLF) bioactive peptides in ovariectomised rats. Food Funct 9(9):4791–4801

    CAS  PubMed  Google Scholar 

  • Pandey M, Kapila R, Kapila S (2018) Osteoanabolic activity of whey-derived anti-oxidative (MHIRL and YVEEL) and angiotensin-converting enzyme inhibitory (YLLF, ALPMHIR, IPA and WLAHK) bioactivepeptides. Peptides 99:1–7

    CAS  PubMed  Google Scholar 

  • Reddi S, Shanmugam VP, Tanedjeu KS, Kapila S, Kapila R (2016) Effect of buffalo casein-derived novel bioactive peptides on osteoblast differentiation. Eur J Nutr 57:593–605

    PubMed  Google Scholar 

  • Segura-Campos MR, Chel-Guerrero LA, Betancur-Ancona DA (2011) Purification of angiotensin I—converting enzyme inhibitory peptides from a cowpea (Vigna unguiculata) enzymatic hydrolysate. Process Biochem 46:864–872

    CAS  Google Scholar 

  • Shanmugam VP, Kapila S, Kemgang Sonfack T, Kapila R (2015) Antioxidative peptide derived from enzymatic digestion of buffalo casein. Int Dairy J 42:1–5

    CAS  Google Scholar 

  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    CAS  PubMed  Google Scholar 

  • Swaisgood HE (1973) The caseins. CRC Crit Rev Food Technol 3:375–414

    Google Scholar 

  • Tavano OL (2013) Protein Hydrolysis using Proteases: An Important Tool For Food Biotechnology. J Mol Catal B Enzym 90:1–11

    CAS  Google Scholar 

  • Vij R, Reddi S, Kapila S, Kapila R (2016) Transepithelial transport of milk derived bioactive peptide VLPVPQK. Food Chem 190:681–688

    CAS  PubMed  Google Scholar 

  • Xu R (2009) Effect of whey protein on the proliferation and differentiation of osteoblasts. J Dairy Sci 92:3012–3018

    Google Scholar 

  • Yamamoto N, Maeno M, Takano T (1990) Purification and characterisation of anantihypertensive peptid from yoghurt-like product fermented by Lactobacillus helveticus CPN4. J Dairy Sci 82:1388–1393

    Google Scholar 

Download references

Acknowledgements

The authors thank the Director of National Dairy Research Institute for providing facilities.

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The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Department of Veterinary Biochemistry, Rajiv Gandhi Institute of Veterinary Education and Research, Kurumbapet, Puducherry, 605 009, India

    Venkatesa Perumal Shanmugam

  2. Animal Biochemistry Division, National Dairy Research Institute, Karnal, Haryana State, 132 001, India

    Suman Kapila, Srinu Reddi & Rajeev Kapila

  3. Persea Naturals LLC, State College, PA, 16803, USA

    Tanedjeu Sonfack Kemgang

  4. School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India

    Subramanian Muthukumar

  5. Research Institute in Semiochemistry and Applied Ethology (IRSEA), 84400, Quartier Salignan, APT, France

    Durairaj Rajesh

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  1. Venkatesa Perumal Shanmugam
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  3. Tanedjeu Sonfack Kemgang
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Correspondence to Venkatesa Perumal Shanmugam.

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Shanmugam, V.P., Kapila, S., Kemgang, T.S. et al. Isolation and Characterization of Angiotensin Converting Enzyme Inhibitory Peptide from Buffalo Casein. Int J Pept Res Ther 27, 1481–1491 (2021). https://doi.org/10.1007/s10989-021-10185-0

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  • DOI: https://doi.org/10.1007/s10989-021-10185-0

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