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Evaluation of Antidiabetic Activities of Casein Hydrolysates by a Bacillus Metalloendopeptidase

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Abstract

Enzymatic hydrolysis is commonly used to produce bioactive peptides from protein such as casein that is rich in bioactive peptide sequences. In this study, a Bacillus metalloendopeptidase (PROTIN SD-NY10) was used to hydrolyze casein to produce bioactive peptides with antidiabetic and antioxidant activities. Several factors affecting the hydrolysis were assessed such as hydrolysis time, metalloendopeptidase concentration, casein concentration, pH, and temperature. The results showed that casein could be effectively hydrolyzed by the metalloendopeptidase, and the casein hydrolysates were shown with high inhibitory activities on α-glucosidase and α-amylase, as well as high antioxidant activity. The high inhibitory activities on α-glucosidase (68.5–80.55%) and α-amylase (74.10–77.15%) were obtained under the selected hydrolysis conditions (pH 7.5, 40 °C, 1% metalloendopeptidase, 10% casein, and 3 h). Meanwhile, the high DPPH radical scavenging activity (55.02–69.40%) could also be obtained under the same hydrolysis conditions. Therefore, the casein hydrolysate obtained by hydrolysis with a metalloendopeptidase of this study could be explored as a bioactive agent for potential application in functional products.

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References

  1. Adler-Nissen J (1984) Control of the proteolytic reaction and of the level of bitterness in protein hydrolysis processes. J Chem Technol Biotechnol 34(3):215–222

  2. Alenzi EO, Kelley GA (2017) The association of hyperglycemia and diabetes mellitus and the risk of chemotherapy-induced neutropenia among cancer patients: a systematic review with meta-analysis. J Diabetes Complicat 31:267–272

  3. Awuor OL, Edward KM, Betty M, Jackim MF (2017) Optimization of alcalase hydrolysis conditions for production of Dagaa (Rastrineobola argentea) protein hydrolysate with antioxidative properties. Ind Chem.https://doi.org/10.4172/2469-9764.1000122

  4. Belitz HD, Grosch W (1999) Food chemistry, 2nd ed. Springer, New York

  5. Benkerroum N (2010) Antimicrobial peptides generated from milk proteins: a survey and prospects for application in the food industry. Int Dairy J 63:320–338

  6. Carreira RL, Ornellas CBD, Morais HA, Da-Motta S, Silvestre MPC (2003) Effect of precipitation by trichloroacetic acid (TCA) and ultrafiltration profile on the peptide hydrolysates of casein. Cienc Agrotec 27:414–421

  7. Chinedum E, Sanni S, Theressa N, Ebere A (2018) Effect of domestic cooking on the starch digestibility, predicted glycemic indices, polyphenol contents and alpha amylase inhibitory properties of beans (Phaseolis vulgaris) and breadfruit (Treculia africana). Int J Biol Macromol 106:200–206

  8. Choi J, Sabikhi L, Hassan A, Anand S (2011) Bioactive peptides in dairy products. Int J Dairy Technol 65(1):1–12

  9. Clare DA, Swaisgood HE (2000) Bioactive milk peptides: a prospectus. J Dairy Sci 83:1187–1195

  10. Coscueta ER, Amorim MM, Voss GB, Nerli BB, Picó GA, Pintado ME (2016) Bioactive properties of peptides obtained from Argentinian defatted soy flour protein by Corolase PP hydrolysis. Food Chem 198:36–44

  11. De Oliveira MR, Silva TJ, Barros E, Guimarães VM, Baracat-Pereira MC, Eller MR, Dos Reis Coimbra JS, de Oliveira EB (2018) Anti-hypertensive peptides derived from caseins: mechanism of physiological action, production bioprocesses, and challenges for food applications. Appl Biochem Biotechnol 185(4):884–908

  12. De Simone C, Picariello G, Mamone G, Stiuso P, Dicitore A, Vanacore D, Chianese L, Addeo F, Ferranti P (2009) Characterisation and cytomodulatory properties of peptides from Mozzarella di Bufala Campana cheese whey. J Pept Sci 15:251–258

  13. Dong H, Li M, Zhu F, Liu F, Huang J (2012) Inhibitory potential of trilobatin from Lithocarpus polystachyus Rehd against a glucosidase and a-amylase linked to type 2 diabetes. Food Chem 130:261–266

  14. Dziuba M, Darewicz M (2007) Food proteins as precursors of bioactive peptides: classification into families. Food Sci Technol Int 13:393–404

  15. Fan J, He J, Zhuang Y, Sun L (2012) Purification and identification of antioxidant peptides from enzymatic hydrolysates of Tilapia (Oreochromis niloticus) frame protein. Molecules 17(11):12836–12850

  16. Gobbetti M, Minervini F, Rizzello CG (2004) Angiotensin I-converting enzyme-inhibitory and antimicrobial bioactive peptides. Int J Dairy Technol 57:172–188

  17. Hartmann R, Meisel H (2007) Food-derived peptides with biological activity: from research to food applications. Curr Opin Biotechnol 18:163–169

  18. Hatta E, Matsumoto K, Honda Y (2015) Bacillolysin, papain, and subtilisin improve the quality of gluten-free rice bread. J Cereal Sci 61:41–47

  19. Ibrahim MA, Bester MJ, Neitz AW, Gaspar ARM (2018) Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates. Biomed Pharmacother 107:234–242

  20. Jan F, Kumar S, Jha R (2016) Effect of boiling on the antidiabetic property of enzyme treated sheep milk casein. Vet World 9(10):1152–1156

  21. Karami Z, Akbari-adergani B (2019) Bioactive food derived peptides: a review on correlation between structure of bioactive peptides and their functional properties. J Food Sci Technol 56:535. https://doi.org/10.1007/s13197-018-3549-4

  22. Kim SK, Wijesekara I (2010) Development and biological activities of marine-derived bioactive peptides: a review. J Funct Foods 2(1):1–9

  23. Kumar D, Chatli MK, Singh R, Mehta N, Kumar P (2016) Enzymatic hydrolysis of camel milk casein and its antioxidant properties. Dairy Sci Technol 96(3):391–404

  24. Lacroix IME, Li-Chan ECY (2012) Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int Dairy J 25(2):97–102

  25. Loizzo MR, Marrelli M, Pugliese A, Conforti F, Nadjafi F, Menichini F, Tundis R (2016) Crocus cancellatus subsp. damascenus stigmas: chemical profile, and inhibition of α-amylase, α-glucosidase and lipase, key enzymes related to type 2 diabetes and obesity. J Enzyme Inhib Med Chem 31:212–218

  26. Mackie IM (1982) Fish protein hydrolysates. Process Biochem 17:26–28

  27. Madureira AR, Tavares T, Gomes AM, Pintado ME, Malcata FX (2010) Invited review: physiological properties of bioactive peptides obtained fromwhey proteins. J Dairy Sci 93:437–455

  28. McCarthy R, Mills S, Ross RP, Fitzgerald GF, Stanton C (2014) Bioactive peptides from casein and whey proteins. Milk Dairy Prod Funct Foods.https://doi.org/10.1002/9781118635056.ch2

  29. Mi ES, Awad S (2016) In vivo anti-diabetic and biological activities of milk protein and milk protein hydrolyaste. Adv Dairy Res.https://doi.org/10.4172/2329-888x.1000154

  30. Miao J, Liao W, Pan Z, Wang Q, Duan S, Xiao S, Yang Z, Cao Y (2019) Isolation and identification of iron-chelating peptides from casein hydrolysates. Food Funct.https://doi.org/10.1039/c8fo02414f

  31. Mudgil P, Kamal H, Yuen GC, Maqsood S (2018) Characterization and identification of novel antidiabetic and anti-obesity peptides from camel milk protein hydrolysates. Food Chem 259:46–54

  32. Normah I, Jamilah N, Saariand B, Yaakob Che man (2005) Optimization of hydrolysis conditions for the production of threadfin bream (Nemipterus japonicus) hydrolysate by alcalase. J Muscle Foods 16:87–102

  33. Omeara GM, Munro PA (1984) Effects of reaction variables on the hydrolysis of lean beef tissue by alcalase. Meat Sci 11:227–238

  34. Pacheco-Aguilar R, Mazorra-Manzano MA, Ramírez-Suárez JC (2008) Functional properties of fish protein hydrolysates from Pacific whiting (Merluccius productus) muscle produced by a commercial protease. Food Chem 109(4):782–789

  35. Pihlanto A (2001) Bioactive peptides derived from bovine whey proteins: opioid and ace-inhibitory peptides. Trends Food Sci Technol 11:347–356

  36. Quaglia GB, Orban E (1987) Enzymatic solubilisation of proteins of sardine (Sardina pilchardus) by commercial proteases. J Sci Food Agric 38:263–269

  37. Rajendran P, Nandakumar N, Rengarajan T, Palaniswami R, Gnanadhas EN, Lakshminarasaiah U. Gopas J, Nishigaki I (2014) Antioxidants and human diseases. Clin Chim Acta 436:332–347

  38. Ren Y, Liang K, Jin Y, Zhang M, Chen Y, Wu H, Lai F (2016) Identification and characterization of two novel a-glucosidase inhibitory oligopeptides from hemp (Cannabis sativa L.) seed protein. J Fun Foods 26:439–450

  39. Ren X, Zheng S, Han T, Chen Y, Liu W, Hou PC, Hu Y (2017) Hyperglycemia and outcomes of medical intensive care unit patients with and without a history of diabetes mellitus in a Chinese population. Intensive Care Med 43:144–145

  40. Sánchez A, Vázquez A (2017) Bioactive peptides: a review. Food Qual Saf 1(1):29–46

  41. Shahidi F, Han XQ, Synowiecki J (1995) Production and characteristics of protein hydrolysates from capelin (Mallotus villosus). Food Chem 53:285–293

  42. Shu G, Zhang B, Zhang Q, Wan H, Li H (2016) Effect of temperature, pH, enzyme to substrate ratio, substrate concentration and time on the antioxidative activity of hydrolysates from goat milk casein by alcalase. Acta Univ Cibiniensis E 20(2):29–38

  43. Shu G, Huang J, Bao C, Meng J, Chen H, Cao J (2018) Effect of different proteases on the degree of hydrolysis and angiotensin I-converting enzyme-inhibitory activity in goat and cow milk. Biomolecules 8(4):101. https://doi.org/10.3390/biom8040101

  44. Teschemacher H, Koch G, Brantl V (1997) Milk protein-derived opioid receptor ligands. Biopolymers 43:99–117

  45. Tidona F, Criscione A, Guastella AM, Zuccaro A, Bordonaro S, Marletta D (2009) Bioactive peptides in dairy products. Ital J Anim Sci 8(3):315–340

  46. Tomatsu M, Shimakage A, Shinbo M, Yamada S, Takahashi S (2013) Novel angiotensin I-converting enzyme inhibitory peptides derived from soya milk. Food Chem 136(2):612–616

  47. Tu M, Liu H, Zhang R, Chen H, Fan F, Shi P, Xu X, Lu W, Du M (2018) Bioactive hydrolysates from casein: generation, identification, and in silico toxicity and allergenicity prediction of peptides. J Sci Food Agric 98(9):3416–3426

  48. Vilcacundo R, Martínez-Villaluenga C, Hernández-Ledesma B (2017) Release of dipeptidyl peptidase IV, α-amylase and α-glucosidase inhibitory peptides from quinoa (Chenopodium quinoa Willd.) during in vitro simulated gastrointestinal digestion. J Fun Foods 35:531–539

  49. Wang J, Su Y, Jia F, Jin H (2013) Characterization of casein hydrolysates derived from enzymatic hydrolysis. Chem Cent J 7(1):62. https://doi.org/10.1186/1752-153x-7-62

  50. Wang J, Du K, Fang L, Liu C, Min W, Liu J (2018) Evaluation of the antidiabetic activity of hydrolyzed peptides derived from Juglans mandshurica Maxim. fruits in insulin-resistant HepG2 cells and type 2 diabetic mice. J Food Biochem 42(3):e12518. https://doi.org/10.1111/jfbc.12518

  51. World Health Organization (2016) Diabetes fact sheet. http://www.who.int/mediacentre/factsheets/fs312/en. Accessed 25 May 2016

  52. Xu Q, Hong H, Wu J, Yan X (2019) Bioavailability of bioactive peptides derived from food proteins across the intestinal epithelial membrane: a review. Trends Food Sci Technol 86:399–411

  53. Yu J, Wang L, Walzem RL, Miller EG, Pike LM, Patil BS (2005) Antioxidant activity of citrus limonoids, flavonoids, and coumarins. J Agric Food Chem 53(6):2009–2014

  54. Zhang H-J, Han J-M, Liu D-C (2007) Study on double low rapeseed protein isolated and its antioxidant properties by alcalase hydrolysis. Grain Oil Process 12:77–80

  55. Zou Z, Xi W, Hu Y, Nie C, Zhou Z (2016) Antioxidant activity of citrus fruits. Food Chem 196:885–896

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Acknowledgements

This work was financially supported by The National Key Research and Development Program of China (2018YFC1604302), National Natural Science Foundation of China (No. 31871823), and 2019 Basic Research Program-Food Specifity (PXM2019_014213_000007).

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Correspondence to Zhennai Yang.

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Megrous, S., Al-Dalali, S., Zhao, X. et al. Evaluation of Antidiabetic Activities of Casein Hydrolysates by a Bacillus Metalloendopeptidase. Int J Pept Res Ther (2020). https://doi.org/10.1007/s10989-020-10045-3

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Keywords

  • Metalloendopeptidase
  • Casein hydrolysate
  • Antidiabetic
  • Antioxidant