Analysis of the Mechanism and Changes in Law of DPP-IV Inhibition Activity of Casein Digestion in Vitro

Abstract

Abstract: In recent years, milk proteins have become an important potential source of DPP-IV inhibitory peptides. In this paper, bovine casein was subjected to the in vitro gastrointestinal digestion, and the digestive properties and DPP-IV inhibitory activities of casein hydrolysates during digestion were determined. Furthermore, peptides with typical structure features of DPP-IV inhibitory peptides were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) in order to elucidate the mechanism underlying the change of DPP-IV inhibitory activities of casein hydrolysate during digestion. As a result, the degree of hydrolysis and digestibility increased with the prolongation of digestion time, resulting in the release of small molecular peptides. The DPP-IV inhibition effects also increased during the digestion process, and reached the highest value of 58.04% at 4 h, which was about 2-fold higher than that at 2 h (23.22%). The degree of hydrolysis and protein digestibility had a certain effect on the release of DPP-IV inhibitory peptides. Furthermore, peptides with typical structure features of DPP-IV inhibitory peptides (i.e., Xaa-Pro/Ala- and Trp-Xaa-) were analyzed by LC-MS/MS to explore the mechanism underlying the change of DPP-IV inhibitory activities of casein digests during digestion. The pepsin digestion generated 25 target peptides, and the molecular weight was mainly >5 kD, while the pancreatin digestion produced a total of 48 target peptides with molecular weight <1 kD. Combined with heat map results, the number and content of peptides in casein digests after pepsin-pancreatin digestion were increased by compared with that after pepsin digestion, which was consistent with the trend of DPP-IV inhibitory activities. It indicated that the DPP-IV inhibitory activities of casein digests during in vitro digestion were closely related to the release of Xaa-Pro/Ala- and Trp-Xaa- peptides.

Key words: Liquid chromatographic tandem mass spectrometry (LC–MS/MS), Bovine casein, Peptides, Dipeptidyl peptidase IV inhibitory peptides, Simulated gastrointestinal digestion

CLC Number:

TS201.1

Jing-Jing Qian Mou-Ming Mou-MingZHAO. Analysis of the Mechanism and Changes in Law of DPP-IV Inhibition Activity of Casein Digestion in Vitro[J]. FOOD SCIENCE, 0, (): 0-0.

References

[1]Zimmet P, Alberti K G, Magliano D J, et al.Diabetes mellitus statistics on prevalence and mortality: facts and fallacies[J].Nature Reviews Endocrinology, 2016, 12(10):616-622 [2]Drummond E, Flynn S, Whelan H, et al.Casein hydrolysate with glycemic control properties: evidence from cells,animal models,and humans[J].Journal of Agricultural and Food Chemistry, 2018, 66(17):4352-4363 [3]Nongonierma A B, Hennemann M, Paolella S, et al.Generation of wheat gluten hydrolysates with dipeptidyl peptidase IV (DPP-IV) inhibitory properties[J].Food & Function, 2017, 8(6):2249-2257 [4]Song J J, Wang Q, Du M, et al.Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates[J].Journal of Dairy Science, 2017, 100(9):6885-6894 [5]Hsieh C, Wang T, Hung C, et al.In silico,in vitro and in vivo analyses of dipeptidyl peptidase IV inhibitory activity and the antidiabetic effect of sodium caseinate hydrolysate[J].Food & function, 2016, 7(2):1122-1128 [6]Nongonierma, Alice B, and Richard J.FitzGerald. Investigation of the potential of hemp, pea, rice and soy protein hydrolysates as a source of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Digestion: Research and Current Opinion 6.1-3 (2015): 19-29.[J].Food Digestion: Research and Current Opinion, 2015, 6(1-3):19-29 [7]Hatanaka T, Kawakami K, Uraji M.Inhibitory effect of collagen-derived tripeptides on dipeptidyl peptidase-IV activity[J].Journal of enzyme inhibition and medicinal chemistry, 2014, 29(6):823-828 [8]Liu R, Cheng J, Wu H.Discovery of food-derived dipeptidyl peptidase IV inhibitory peptides: a review[J].International Journal of Molecular Sciences, 2019, 20(3):463-463 [9]Nongonierma A B, FitzGerald R J.Structure activity relationship modelling of milk protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity[J]. Peptides, 2016, 79:1-7.[J].peptides, 2016, (79):1-7 [10]Nongonierma A B, FitzGerald R J.Learnings from quantitative structure-activity relationship (QSAR) studies with respect to food protein-derived bioactive peptides: a review[J].RSC Advances, 2016, 6(79):75400-75413 [11]Nongonierma A B, FitzGerald R J.Inhibition of dipeptidyl peptidase IV (DPP-IV) by proline containing casein-derived peptides[J].Journal of Functional Foods, 2013, 5(4):1909-1917 [12]Nongonierma A B, FitzGerald R J.Inhibition of dipeptidyl peptidase IV (DPP-IV) by tryptophan containing dipeptides[J].Food & function, 2013, 4(12):1843-1849 [13]Teschemacher H, Koch G, Brantl V.Milk protein-derived opioid receptor ligands[J].BIOPOLYMERS, 1997, 43(2):99-117 [14]Meisel H.Biochemical Properties of peptides encrypted in bovine milk proteins[J].Current Medicinal Chemistry, 2005, 12(16):1905-1919 [15]Yayeh T, Leem Y, Kim K, et al.Administration of alphas1 -casein hydrolysate increases sleep and modulates GABAA receptor subunit expression[J].Biomolecules & Therapeutics, 2018, 26(3):268-273 [16]Tagliazucchi D, Shamsia S, Helal A, et al.Angiotensin-converting enzyme inhibitory peptides from goats' milk released by in vitro gastro-intestinal digestion[J]. International Dairy Journal, 2017, 71:6-16.[J].International Dairy Journal, 2017, (71):6-16 [17]Hidayat K, Du X, Shi B M.Milk in the prevention and management of type 2 diabetes mellitus: the potential role of milk proteins[J]. Diabetes/Metabolism Research and Reviews, 2019:e3187.[J].Diabetes/Metabolism Research and Reviews, 2019, :3187- [18]张颖.牛、羊乳酪蛋白源DPP-IV抑制肽的制备、鉴定及抑制机理研究[D]. 中国农业大学, 2016. [19]Zhang Y, Chen R, Zuo F, et al.Comparison of dipeptidyl peptidase IV-inhibitory activity of peptides from bovine and caprine milk casein by in silico and in vitro analyses[J]. International Dairy Journal, 2016, 53:37-44.[J].International Dairy Journa, 2016, (53):37-44 [20]Tagliazucchi D, Martini S, Shamsia S, et al.Biological activities and peptidomic profile of in vitro-digested cow, camel, goat and sheep milk[J]. International Dairy Journal, 2018, 81:19-27.[J].International Dairy Journal, 2018, (81):19-27 [21]You L, Zhao M, Regenstein J M, et al.Changes in the antioxidant activity of loach ( Misgurnus anguillicaudatus) protein hydrolysates during a simulated gastrointestinal digestion[J].Food Chemistry, 2010, 120(3):810-816 [22]Nielsen P M, Petersen D, Dambmann C.Improved method for determining food protein degree of hydrolysis[J].Journal of Food Science, 2001, 66(5):642-646 [23]Silveira S T, Martínez-Maqueda D, Recio I, et al.Dipeptidyl peptidase-IV inhibitory peptides generated by tryptic hydrolysis of a whey protein concentrate rich in β-lactoglobulin[J].Food Chemistry, 2013, 141(2):1072-1077 [24]Zheng L, Ren J, Su G, et al.Comparison of in vitro digestion characteristics and antioxidant activity of hot- and cold-pressed peanut meals[J].Food Chemistry, 2013, 141(4):4246-4252 [25]Goodman B E.Insights into digestion and absorption of major nutrients in humans[J].Advances in Physiology Education, 2010, 34(2):44-53 [26]Ma Y, Xiong Y L.Antioxidant and bile acid binding activity of buckwheat protein in vitro digests[J].Journal of Agricultural and Food Chemistry, 2009, 57(10):4372-4380 [27]Pratley R E, Salsali A.Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes[J].Current Medical Research and Opinion, 2007, 23(4):919-931 [28]Lacroix I M E, Li-Chan E C Y.Isolation and characterization of peptides with dipeptidyl peptidase-IV inhibitory activity from pepsin-treated bovine whey proteins[J]. Peptides, 2014, 54:39-48.[J].peptides, 2014, (54):39-48 [29]Le Maux S, Nongonierma A B, Murray B, et al.Identification of short peptide sequences in the nanofiltration permeate of a bioactive whey protein hydrolysate[J]. Food Research International, 2015, 77:534-539.[J].Food Research International, 2015, 77:534-539 [30]Agudelo R A, Gauthier S F, Pouliot Y, et al.Kinetics of peptide fraction release duringin vitro digestion of casein[J].Journal of the Science of Food and Agriculture, 2004, 84(4):325-332 [31]Nongonierma A B, FitzGerald R J.An in silico model to predict the potential of dietary proteins as sources of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides[J]. Food Chemistry, 2014, 165:489-498.[J].Food Chemistry, 2014, (165):489-498 [32]Iwona S, Dorota N.The use of UniProtKBBIOPEP for the analysis of oat globulin physicochemical parameters and bioactivity[J].Czech Journal of Food Sciences, 2018, 36(No. 2):119-125 [33]王镜岩.生物化学[Z]. 北京: 高等教育出版社, 2002. [34]Zhang Y, Chen R, Chen X, et al.Dipeptidyl peptidase-IV inhibitory peptides derived from silver carp (Hypophthalmichthys molitrix Val) proteins[J].Journal of Agricultural and Food Chemistry, 2016, 64(4):831-839 [35]Maruyama S, Ohmori T, Nakagami T.Prolylendopeptidase inhibitory activity of a glial fibrillary acidic protein fragment and other proline-rich peptides[J].Bioscience, Biotechnology, and Biochemistry, 1996, 60(2):358-359