Milk-derived bioactive peptides and their health promoting effects: a potential role in atherosclerosis

British Journal of Clinical Pharmacology

Volumn 83, Issue 1, 2017, Pages 152-162

  Marcone, Simone ^a   Belton, Orina ^a   Fitzgerald, Desmond J ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

atherosclerosis; bioactive peptides; cardiovascular disease; immunomodulation; inflammation; milk proteins

Indexed keywords

ANTICOAGULANT AGENT; ANTIHYPERTENSIVE AGENT; ANTIINFLAMMATORY AGENT; ANTILIPEMIC AGENT; ANTIOXIDANT; IMMUNOMODULATING AGENT; LIPID; MILK PROTEIN; PEPTIDE;

ANTICOAGULATION; ANTIHYPERTENSIVE ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ATHEROGENESIS; ATHEROSCLEROSIS; BIOLOGICAL ACTIVITY; CARDIOVASCULAR DISEASE; CHRONIC DISEASE; DIET SUPPLEMENTATION; FUNCTIONAL FOOD; GLYCEMIC CONTROL; HEALTH PROMOTION; HUMAN; HYPERTENSION; IMMUNOMODULATION; INSULIN RELEASE; INSULIN RESISTANCE; LIPID BLOOD LEVEL; MEDLINE; MILK; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; RISK REDUCTION; SCOPUS; CHEMISTRY; DIETARY SUPPLEMENT; FERMENTATION; ISOLATION AND PURIFICATION;

ATHEROSCLEROSIS; DIETARY SUPPLEMENTS; FERMENTATION; HUMANS; MILK PROTEINS; PEPTIDES;

EID: 84977514840     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.13002     Document Type: Review

References (121)

1. Schanbacher FL, Talhouk RS, Murray FA. Biology and origin of bioactive peptides in milk. Livest Prod Sci 1997; 50: 105–23.
2. Wong DW, Camirand WM, Pavlath AE. Structures and functionalities of milk proteins. Crit Rev Food Sci Nutr 1996; 36: 807–44.
3. Korhonen H, Pihlanto A. Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum. Curr Pharm Des 2007; 13: 829–43.
4. Yamamoto N. Antihypertensive peptides derived from food proteins. Biopolymers 1997; 43: 129–34.
5. Lahov E, Regelson W. Antibacterial and immunostimulating casein-derived substances from milk: casecidin, isracidin peptides. Food Chem Toxicol 1996; 34: 131–45.
6. Meisel H. Biochemical properties of regulatory peptides derived from milk proteins. Biopolymers 1997; 43: 119–28.
7. Dziuba J, Minkiewicz P, Nalecz D, Iwaniak A. Database of biologically active peptide sequences. Nahrung 1999; 43: 190–5.
8. Gobbetti M, Stepaniak L, De Angelis M, Corsetti A, Di Cagno R. Latent bioactive peptides in milk proteins: proteolytic activation and significance in dairy processing. Crit Rev Food Sci Nutr 2002; 42: 223–39.
9. Meisel H. Multifunctional peptides encrypted in milk proteins. Biofactors 2004; 21: 55–61.
10. Malkoski M, Dashper SG, O'Brien-Simpson NM, Talbo GH, Macris M, Cross KJ, et al. Kappacin, a novel antibacterial peptide from bovine milk. Antimicrob Agents Chemother 2001; 45: 2309–15.
11. Jakala P, Pere E, Lehtinen R, Turpeinen A, Korpela R, Vapaatalo H. Cardiovascular activity of milk casein-derived tripeptides and plant sterols in spontaneously hypertensive rats. J Physiol Pharmacol 2009; 60: 11–20.
12. Sipola M, Finckenberg P, Santisteban J, Korpela R, Vapaatalo H, Nurminen ML. Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats. J Physiol Pharmacol 2001; 52: 745–54.
13. Hirota T, Ohki K, Kawagishi R, Kajimoto Y, Mizuno S, Nakamura Y, et al. Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: contribution of the inhibitory action of angiotensin-converting enzyme. Hypertension Res 2007; 30: 489–96.
14. Pearson T. Cardiovascular update: risk, guidelines, and recommendations. Workplace Health Saf 2015; 63: 376–80.
15. FitzGerald RJ, Murray BA, Walsh DJ. Hypotensive peptides from milk proteins. J Nutr 2004; 134: 980S–8S.
16. Vercruysse L, Van Camp J, Smagghe G. ACE inhibitory peptides derived from enzymatic hydrolysates of animal muscle protein: a review. J Agric Food Chem 2005; 53: 8106–15.
17. FitzGerald RJ, Meisel H. Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme. Br J Nutr 2000; 84 (Suppl 1): S33–7.
18. Nakamura Y, Yamamoto N, Sakai K, Takano T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J Dairy Sci 1995; 78: 1253–7.
19. Seppo L, Jauhiainen T, Poussa T, Korpela R. A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutr 2003; 77: 326–30.
20. Murakami M, Tonouchi H, Takahashi R, Kitazawa H, Kawai Y, Negishi H, et al. Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product. J Dairy Sci 2004; 87: 1967–74.
21. Boelsma E, Kloek J. Lactotripeptides and antihypertensive effects: a critical review. Br J Nutr 2009; 101: 776–86.
22. Boelsma E, Kloek J. IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial. Nutr J 2010; 9: 52.
23. Fujita H, Usui H, Kurahashi K, Yoshikawa M. Isolation and characterization of ovokinin, a bradykinin B1 agonist peptide derived from ovalbumin. Peptides 1995; 16: 785–90.
24. Matoba N, Usui H, Fujita H, Yoshikawa M. A novel anti-hypertensive peptide derived from ovalbumin induces nitric oxide-mediated vasorelaxation in an isolated SHR mesenteric artery. FEBS Lett 1999; 452: 181–4.
25. Erdmann K, Grosser N, Schipporeit K, Schroder H. The ACE inhibitory dipeptide Met-Tyr diminishes free radical formation in human endothelial cells via induction of heme oxygenase-1 and ferritin. J Nutr 2006; 136: 2148–52.
26. Nurminen ML, Sipola M, Kaarto H, Pihlanto-Leppala A, Piilola K, Korpela R, et al. Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats. Life Sci 2000; 66: 1535–43.
27. Fiat AM, Levy-Toledano S, Caen JP, Jolles P. Biologically active peptides of casein and lactotransferrin implicated in platelet function. J Dairy Res 1989; 56: 351–5.
28. Leonil J, Molle D. Liberation of tryptic fragments from caseinomacropeptide of bovine kappa-casein involved in platelet function. Kinetic study. Biochem J 1990; 271: 247–52.
29. Jolles P, Levy-Toledano S, Fiat AM, Soria C, Gillessen D, Thomaidis A, et al. Analogy between fibrinogen and casein. Effect of an undecapeptide isolated from kappa-casein on platelet function. Eur J Biochem 1986; 158: 379–82.
30. Manso MA, Escudero C, Alijo M, Lopez-Fandino R. Platelet aggregation inhibitory activity of bovine, ovine, and caprine kappa-casein macropeptides and their tryptic hydrolysates. J Food Prot 2002; 65: 1992–6.
31. Qian ZY, Jolles P, Migliore-Samour D, Schoentgen F, Fiat AM. Sheep kappa-casein peptides inhibit platelet aggregation. Biochim Biophys Acta 1995; 1244: 411–7.
32. Bal dit Sollier C, Drouet L, Pignaud G, Chevallier C, Caen J, Fiat AM, et al. Effect of kappa-casein split peptides on platelet aggregation and on thrombus formation in the guinea-pig. Thromb Res 1996; 81: 427–37.
33. Raha S, Dosquet C, Abgrall JF, Jolles P, Fiat AM, Caen JP. KRDS–a tetrapeptide derived from lactotransferrin–inhibits binding of monoclonal antibody against glycoprotein IIb-IIIa on ADP-stimulated platelets and megakaryocytes. Blood 1988; 72: 172–8.
34. Mazoyer E, Levy-Toledano S, Rendu F, Hermant L, Lu H, Fiat AM, et al. KRDS, a new peptide derived from human lactotransferrin, inhibits platelet aggregation and release reaction. Eur J Biochem 1990; 194: 43–9.
35. Drouet L, Bal dit Sollier C, Cisse M, Pignaud G, Mazoyer E, Fiat AM, et al. The antithrombotic effect of KRDS, a lactotransferrin peptide, compared with RGDS. Nouv Rev Fr Hematol 1990; 32: 59–62.
36. Angiolillo DJ. The evolution of antiplatelet therapy in the treatment of acute coronary syndromes: from aspirin to the present day. Drugs 2012; 72: 2087–116.
37. Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India 2004; 52: 794–804.
38. Brieger K, Schiavone S, Miller FJ Jr, Krause KH. Reactive oxygen species: from health to disease. Swiss Med Wkly 2012; 142: w13659.
39. Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J 1987; 1: 441–5.
40. de Lorgeril M, Salen P, Monjaud I, Delaye J. The 'diet heart' hypothesis in secondary prevention of coronary heart disease. Eur Heart J 1997; 18: 13–8.
41. Simopoulos AP. The Mediterranean diets: What is so special about the diet of Greece? The scientific evidence. J Nutr 2001; 131: 3065S–73S.
42. Suetsuna K, Ukeda H, Ochi H. Isolation and characterization of free radical scavenging activities peptides derived from casein. J Nutr Biochem 2000; 11: 128–31.
43. Hernandez-Ledesma B, Davalos A, Bartolome B, Amigo L. Preparation of antioxidant enzymatic hydrolysates from alpha-lactalbumin and beta-lactoglobulin. Identification of active peptides by HPLC-MS/MS. J Agric Food Chem 2005; 53: 588–93.
44. Chen HM, Muramoto K, Yamauchi F, Fujimoto K, Nokihara K. Antioxidative properties of histidine-containing peptides designed from peptide fragments found in the digests of a soybean protein. J Agric Food Chem 1998; 46: 49–53.
45. Jimenez-Ruiz EI, Calderon de la Barca AM, Sotelo-Mundo RR, Arteaga-Mackinney GE, Valenzuela-Melendez M, Pena-Ramos EA. Partial characterization of ultrafiltrated soy protein hydrolysates with antioxidant and free radical scavenging activities. J Food Sci 2013; 78: C1152–8.
46. Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, et al. Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA Task Force on Risk Reduction, American Heart Association. Circulation 1998; 97: 1876–87.
47. Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet 1986; 2: 933–6.
48. Jabir NR, Siddiqui AN, Firoz CK, Md Ashraf G, Zaidi SK, Khan MS, et al. Current updates on therapeutic advances in the management of cardiovascular diseases. Curr P harm Des 2016; 22: 566–71.
49. Hori G, Wang MF, Chan YC, Komatsu T, Wong Y, Chen TH, et al. Soy protein hydrolyzate with bound phospholipids reduces serum cholesterol levels in hypercholesterolemic adult male volunteers. Biosci Biotechnol Biochem 2001; 65: 72–8.
50. Nagaoka S, Futamura Y, Miwa K, Awano T, Yamauchi K, Kanamaru Y, et al. Identification of novel hypocholesterolemic peptides derived from bovine milk beta-lactoglobulin. Biochem Biophys Res Commun 2001; 281: 11–7.
51. Morikawa K, Kondo I, Kanamaru Y, Nagaoka S. A novel regulatory pathway for cholesterol degradation via lactostatin. Biochem Biophys Res Commun 2007; 352: 697–702.
52. Woodward M, Zhang X, Barzi F, Pan W, Ueshima H, Rodgers A, et al. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region. Diabetes Care 2003; 26: 360–6.
53. Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr 2004; 80: 1246–53.
54. Calbet JA, Holst JJ. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Nutr 2004; 43: 127–39.
55. Claessens M, Saris WH, van Baak MA. Glucagon and insulin responses after ingestion of different amounts of intact and hydrolysed proteins. Br J Nutr 2008; 100: 61–9.
56. Frid AH, Nilsson M, Holst JJ, Bjorck IM. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr 2005; 82: 69–75.
57. Ma J, Stevens JE, Cukier K, Maddox AF, Wishart JM, Jones KL, et al. Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes. Diabetes Care 2009; 32: 1600–2.
58. Belobrajdic DP, McIntosh GH, Owens JA. A high-whey-protein diet reduces body weight gain and alters insulin sensitivity relative to red meat in wistar rats. J Nutr 2004; 134: 1454–8.
59. Liu Z, Jeppesen PB, Gregersen S, Chen X, Hermansen K. Dose- and glucose-dependent effects of amino acids on insulin secretion from isolated mouse islets and clonal INS-1E beta-cells. Rev Diabet Stud 2008; 5: 232–44.
60. Phillips LK, Prins JB. Update on incretin hormones. Ann N Y Acad Sci 2011; 1243: E55–74.
61. Manders RJ, Praet SF, Meex RC, Koopman R, de Roos AL, Wagenmakers AJ, et al. Protein hydrolysate/leucine co-ingestion reduces the prevalence of hyperglycemia in type 2 diabetic patients. Diabetes Care 2006; 29: 2721–2.
62. Manders RJ, Praet SF, Vikstrom MH, Saris WH, van Loon LJ. Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients. Eur J Clin Nutr 2009; 63: 121–6.
63. Brader L, Holm L, Mortensen L, Thomsen C, Astrup A, Holst JJ, et al. Acute effects of casein on postprandial lipemia and incretin responses in type 2 diabetic subjects. Nutr Metab Cardiovasc Dis 2010; 20: 101–9.
64. Cohen AT, Imfeld S, Markham J, Granziera S. The use of aspirin for primary and secondary prevention in venous thromboembolism and other cardiovascular disorders. Thromb Res 2015; 135: 217–25.
65. Golia E, Limongelli G, Natale F, Fimiani F, Maddaloni V, Pariggiano I, et al. Inflammation and cardiovascular disease: from pathogenesis to therapeutic target. Curr Atheroscler Rep 2014; 16: 435.
66. Pellicano R. Gastrointestinal damage by non-steroidal anti-inflammatory drugs: updated clinical considerations. Minerva Gastroenterol Dietol 2014; 60: 255–61.
67. Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol 2014; 70: 1159–72.
68. Aihara K, Ishii H, Yoshida M. Casein-derived tripeptide, Val-Pro-Pro (VPP), modulates monocyte adhesion to vascular endothelium. J Atheroscler Thromb 2009; 16: 594–603.
69. Nielsen DS, Theil PK, Larsen LB, Purup S. Effect of milk hydrolysates on inflammation markers and drug-induced transcriptional alterations in cell-based models. J Anim Sci 2012; 90 (Suppl 4): 403–5.
70. Iskandar MM, Dauletbaev N, Kubow S, Mawji N, Lands LC. Whey protein hydrolysates decrease IL-8 secretion in lipopolysaccharide (LPS)-stimulated respiratory epithelial cells by affecting LPS binding to Toll-like receptor 4. Br J Nutr 2013; 110: 58–68.
71. Piccolomini AF, Iskandar MM, Lands LC, Kubow S. High hydrostatic pressure pre-treatment of whey proteins enhances whey protein hydrolysate inhibition of oxidative stress and IL-8 secretion in intestinal epithelial cells. Food Nutr Res 2012; 56.
72. Haversen L, Ohlsson BG, Hahn-Zoric M, Hanson LA, Mattsby-Baltzer I. Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kappa B. Cell Immunol 2002; 220: 83–95.
73. Puddu P, Latorre D, Carollo M, Catizone A, Ricci G, Valenti P, et al. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells. PLoS One 2011; 6: e22504.
74. Yan D, Kc R, Chen D, Xiao G, Im HJ. Bovine lactoferricin-induced anti-inflammation is, in part, via up-regulation of interleukin-11 by secondary activation of STAT3 in human articular cartilage. J Biol Chem 2013; 288: 31655–69.
75. Yan D, Chen D, Shen J, Xiao G, van Wijnen AJ, Im HJ. Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium. J Cell Physiol 2013; 228: 447–56.
76. Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol 2013; 45: 1730–47.
77. Nakamura T, Hirota T, Mizushima K, Ohki K, Naito Y, Yamamoto N, et al. Milk-derived peptides, Val-Pro-Pro and Ile-Pro-Pro, attenuate atherosclerosis development in apolipoprotein e-deficient mice: a preliminary study. J Med Food 2013; 16: 396–403.
78. Shimizu N, Dairiki K, Ogawa S, Kaneko T. Dietary whey protein hydrolysate suppresses development of atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice. Allergol Int 2006; 55: 185–9.
79. Hatori M, Ohki K, Hirano S, Yang XP, Kuboki H, Abe C. Effects of a casein hydrolysate prepared from Aspergillus oryzae protease on adjuvant arthritis in rats. Biosci Biotechnol Biochem 2008; 72: 1983–91.
80. Marcone S, Haughton K, Simpson PJ, Belton O, Fitzgerald DJ. Milk-derived bioactive peptides inhibit human endothelial-monocyte interactions via PPAR-gamma dependent regulation of NF-kappaB. J Inflamm 2015; 12: 1.
81. Wong CW, Seow HF, Liu AH, Husband AJ, Smithers GW, Watson DL. Modulation of immune responses by bovine beta-casein. Immunol Cell Biol 1996; 74: 323–9.
82. Barta O, Barta VD, Crisman MV, Akers RM. Inhibition of lymphocyte blastogenesis by whey. Am J Vet Res 1991; 52: 247–53.
83. Otani H, Monnai M, Kawasaki Y, Kawakami H, Tanimoto M. Inhibition of mitogen-induced proliferative responses of lymphocytes by bovine kappa-caseinoglycopeptides having different carbohydrate chains. J Dairy Res 1995; 62: 349–57.
84. Laffineur E, Genetet N, Leonil J. Immunomodulatory activity of beta-casein permeate medium fermented by lactic acid bacteria. J Dairy Sci 1996; 79: 2112–20.
85. Kayser H, Meisel H. Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Lett 1996; 383: 18–20.
86. Crouch SP, Slater KJ, Fletcher J. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 1992; 80: 235–40.
87. Paegelow I, Werner H. Immunomodulation by some oligopeptides. Methods Find Exp Clin Pharmacol 1986; 8: 91–5.
88. McFadden RG, Vickers KE. Bradykinin augments the in vitro migration of nonsensitized lymphocytes. Clin Invest Med 1989; 12: 247–53.
89. Anogeianaki A, Angelucci D, Cianchetti E, D'Alessandro M, Maccauro G, Saggini A, et al. Atherosclerosis: a classic inflammatory disease. Int J Immunopathol Pharmacol 2011; 24: 817–25.
90. Tousoulis D, Kampoli AM, Papageorgiou N, Androulakis E, Antoniades C, Toutouzas K, et al. Pathophysiology of atherosclerosis: the role of inflammation. Curr Pharm Des 2011; 17: 4089–110.
91. Mizuno Y, Jacob RF, Mason RP. Inflammation and the development of atherosclerosis. J Atheroscler Thromb 2011; 18: 351–8.
92. Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol 2011; 31: 969–79.
93. Kruth HS. Lipoprotein cholesterol and atherosclerosis. Curr Mol Med 2001; 1: 633–53.
94. Le Brocq M, Leslie SJ, Milliken P, Megson IL. Endothelial dysfunction: from molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal 2008; 10: 1631–74.
95. Kuschert GS, Coulin F, Power CA, Proudfoot AE, Hubbard RE, Hoogewerf AJ, et al. Glycosaminoglycans interact selectively with chemokines and modulate receptor binding and cellular responses. Biochemistry 1999; 38: 12959–68.
96. Rao RM, Yang L, Garcia-Cardena G, Luscinskas FW. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ Res 2007; 101: 234–47.
97. Sasaki M, Jordan P, Welbourne T, Minagar A, Joh T, Itoh M, et al. Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha. BMC Physiol 2005; 5: 3.
98. Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000; 49: 497–505.
99. Wilmer WA, Dixon C, Lu L, Hilbelink T, Rovin BH. A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma. Biochem Biophys Res Commun 2001; 281: 57–62.
100. Perez-Sala D, Cernuda-Morollon E, Canada FJ. Molecular basis for the direct inhibition of AP-1 DNA binding by 15-deoxy-delta 12,14-prostaglandin J2. J Biol Chem 2003; 278: 51251–60.
101. Malinowski J, Klempt M, Clawin-Radecker I, Lorenzen PC, Meisel H. Identification of a NFkappaB inhibitory peptide from tryptic beta-casein hydrolysate. Food Chem 2014; 165: 129–33.
102. Yi L, Chandrasekaran P, Venkatesan S. TLR signaling paralyzes monocyte chemotaxis through synergized effects of p38 MAPK and global Rap-1 activation. PLoS One 2012; 7: e30404.
103. Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 2003; 37: 1043–55.
104. Pihlanto A, Korhonen H. Bioactive peptides and proteins. Adv Food Nutr Res 2003; 47: 175–276.
105. Sanchez-Rivera L, Ares I, Miralles B, Gomez-Ruiz JA, Recio I, Martinez-Larranaga MR, et al. Bioavailability and kinetics of the antihypertensive casein-derived peptide HLPLP in rats. J Agric Food Chem 2014; 62: 11869–75.
106. Maeno M, Yamamoto N, Takano T. Identification of an antihypertensive peptide from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J Dairy Sci 1996; 79: 1316–21.
107. Yamamoto N, Akino A, Takano T. Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. J Dairy Sci 1994; 77: 917–22.
108. Pihlanto-Leppala A, Koskinen P, Piilola K, Tupasela T, Korhonen H. Angiotensin I-converting enzyme inhibitory properties of whey protein digests: concentration and characterization of active peptides. J Dairy Res 2000; 67: 53–64.
109. Mullally MM, Meisel H, FitzGerald RJ. Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine beta-lactoglobulin. FEBS Lett 1997; 402: 99–101.
110. FitzGerald RJ, Meisel H. Lactokinins: whey protein-derived ACE inhibitory peptides. Nahrung 1999; 43: 165–7.
111. Mullally MM, Meisel H, FitzGerald RJ. Synthetic peptides corresponding to alpha-lactalbumin and beta-lactoglobulin sequences with angiotensin-I-converting enzyme inhibitory activity. Biol Chem Hoppe Seyler 1996; 377: 259–60.
112. Smacchi E, Gobbetti M. Bioactive peptides in dairy products: synthesis and interaction with proteolytic enzymes. Food Microbiol 2000; 17: 129–41.
113. Mao X-Y, Ni J-R, Sun W-L, Hao P-P, Fan L. Value-added utilization of yak milk casein for the production of angiotensin-I-converting enzyme inhibitory peptides. Food Chem 2007; 103: 1282–7.
114. Haileselassie SS, Lee BH, Gibbs BF. Purification and identification of potentially bioactive peptides from enzyme-modified cheese. J Dairy Sci 1999; 82: 1612–7.
115. Chabance B, Jolles P, Izquierdo C, Mazoyer E, Francoual C, Drouet L, et al. Characterization of an antithrombotic peptide from kappa-casein in newborn plasma after milk ingestion. Br J Nutr 1995; 73: 583–90.
116. Qian ZY, Jolles P, Migliore-Samour D, Fiat AM. Isolation and characterization of sheep lactoferrin, an inhibitor of platelet aggregation and comparison with human lactoferrin. Biochim Biophys Acta 1995; 1243: 25–32.
117. Chabance B, Marteau P, Rambaud JC, Migliore-Samour D, Boynard M, Perrotin P, et al. Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie 1998; 80: 155–65.
118. Fiat AM, Migliore-Samour D, Jolles P, Drouet L, Bal dit Sollier C, Caen J. Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. J Dairy Sci 1993; 76: 301–10.
119. Contreras MM, Carrón R, Montero MJ, Ramos M, Recio I. Novel casein-derived peptides with antihypertensive activity. Int Dairy J 2009; 19: 566–73.
120. Nagaoka S, Kanamaru Y, Kuzuya Y, Kojima T, Kuwata T. Comparative studies on the serum cholesterol lowering action of whey protein and soybean protein in rats. Biosci Biotechnol Biochem 1992; 56: 1484–5.
121. Zhang X, Beynen AC. Lowering effect of dietary milk-whey protein v. casein on plasma and liver cholesterol concentrations in rats. Br J Nutr 1993; 70: 139–46.