You are on page 1of 9

Small Ruminant Research 101 (2011) 196–204

Contents lists available at SciVerse ScienceDirect

Small Ruminant Research
journal homepage: www.elsevier.com/locate/smallrumres

Review

Bioactive components of ovine and caprine cheese whey夽
Blanca Hernández-Ledesma, Mercedes Ramos, José Ángel Gómez-Ruiz ∗
Institute of Food Science Research (CIAL, CSIC-UAM), Nicolás Cabrera 9, Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Cheese whey, also known as sweet whey, is a by-product of cheese-making that con-
Available online 22 October 2011 tains many valuable constituents. Among them, whey proteins stand out for their high
nutritional value in terms of biological value and composition in essential amino acids. In
Keywords: recent years, the increasing demand for caprine and ovine cheeses has produced impor-
Cheese whey
tant amounts of whey from these species, boosting research on the biological activities
Sheep and goat whey proteins
of its constituent proteins. Different bioactivities have been associated to these proteins,
Bioactivity
Bioactive peptides
among them antihypertensive, antimicrobial, opioid, antioxidant and immunomodulant
Health activity being the most studied. Although biological activities are present in the intact
proteins, in many cases whey proteins act as precursors of bioactive peptides that are
released from the hydrolysis of these proteins with different enzymes. This review presents
an overview of the different biological activities described for caprine and ovine cheese
whey proteins as well as for other whey components such as lactose, oligosaccharides or
minerals.
© 2011 Elsevier B.V. All rights reserved.

1. Introduction their reducing properties of chronic diseases risk (Correia
and Cruz, 2006).
Goat and sheep milk have traditionally been a vital The average protein content in sheep milk (5.8%, w/w)
part of the cultural heritage and national economy of is higher than in goat (4.6%, w/w) or cow milk (3.3%, w/w).
Mediterranean countries, particularly France, Italy, Spain Whey is the soluble fraction of milk, rich in proteins, min-
and Greece. Rearing goats and sheep is gaining importance erals and lactose that are separated from casein during the
worldwide, and the production of derived dairy prod- manufacture of cheese or casein. Rennet-driven coagula-
ucts has experienced an important increase, making them tion releases the sweet whey or cheese whey, while that
of particular economic value in these countries (Pandya obtained from the mineral or lactic acid coagulated casein is
and Ghodke, 2007; Raynal-Ljutovaca et al., 2008). Excel- called acid whey. Whey from ovine and caprine species has
lent cheeses are made with goat and sheep milk. Some a unique protein composition that depends on factors, such
of the best known are Roquefort, Peccorino Romano, Feta, as the type of whey (acid or sweet), the time of the year,
Manchego, Bryndza and the French goat milk cheeses. Spe- the type of feed, the stage of lactation and the quality of
cific texture and taste of sheep and goat milk, as well processing. Distribution of individual proteins in sheep and
as their nutritional and functional properties, have made goat milk whey and its comparison with cow milk is shown
them a valuable and healthier alternative to cow milk. Even, in Table 1. The major whey proteins are ␤-lactoglobulin
many authors have called them “functional foods” because (␤-Lg) and ␣-lactalbumin (␣-La). Immunoglobulins (Igs),
of their modulating activity of physiological functions and serum albumin and proteose-peptones are present in
smaller concentrations. Another soluble protein found in
small amounts is lactoferrin (LF) and, in the case of cheese
夽 This paper is part of the special issue entitled Products from Small whey, caseino-macropeptide (CMP) is also present. Other
Ruminants, Guest Edited by A. Govaris and G. Moatsou. components including lactose, oligosaccharides or miner-
∗ Corresponding author. Tel.: +34 91 5622900; fax: +34 91 5644853.
als are also important in the whey.
E-mail address: joseangel.gomez.ruiz@csic.es (J.Á. Gómez-Ruiz).

0921-4488/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.smallrumres.2011.09.040

. Fox et al. sive immunity with IgG (Sutton and Alston-Mills. More. sport meals.0–9.3 explain the high consumption of this kind of products is Lactoferrin 0. One of the reasons to Serum albumin 0. body weight by providing satiety signals that affect both in last decades.26–0. could also act as source of numerous bioactive peptides.0 1. Compared to bovine proteins. 2009). Table 1 such as lactose. antioxidant. Hahn et al. Milk whey whey proteins. Since primary structures of these proteins ipate in the digestion of milk lipids during the neonatal show a great homology with those observed for bovine pro.. some of them shared with peptides derived proteins exhibit a range of biological activities that influ. marized in Table 2. 1983.5 1.3 kDa. ˇ-Lactoglobulin tance to disease. exert specific biological activities.3–0.2–1.0 ␤-Lactoglobulin 3.55–0.. from its hydrolysis. sheep and goat milk included in this review. intestinal uptake of retinol. 2000).2–4.05–0. oligosaccharides and minerals will be also Concentration of the main whey proteins in cow. Hernández-Ledesma et al. Moreover. . In addition.2 0. soluble and globular protein. ovine and caprine ␤-Lg are shown in Table 1. suggested the role of this protein as a resistant carrier 2008). such as antihypertensive. 2010). Other physiological activities of the individual products and its role upon human health.. containing 162 2008.10 0.7–5.0 2.. whey has been viewed as a by-product of tional food component to contribute to the regulation of dairy industry with little value for the consumers. ␤- mineral binding (Yalcin. Reported activities for ␤-Lg are sum- process during food production (e. bioactivity of other components of cheese whey. sheep. or bovine. are described in this review.6 0.1 protein cookies and in tablet form. Lg is a small. (Storry et al.2–2. capable to ␤-Lg is the major whey protein found in cow. and resis. termed bioactive peptides.8 powdered beverages.7–7. nutrition bars. The homology of ␤-Lg tertiary structure matic hydrolysis. 2006. whey proteins seem to have potential as a func- Traditionally. whey protein-derived bioactive peptides with the plasma retinol-binding protein as well as its high are mainly produced by the second step using different stability to proteolytic action of digestive enzymes has enzymes or by chemical synthesis (Morris and Fitzgerald. triglycerides. 2007). opioid. amino acids in a single peptide chain with a molecular tive peptides that can be released by either technological weight of 18. sheep and goat origin. high- ␣-Lactalbumin 1.8–10. Other possible functions have been described and caprine whey proteins and derived-peptides.6 0. 2. immunomodulant. metabolic responses to absorbed nutrients. period. and long-chain it is predictable that ovine and caprine whey proteins fatty acids in pre-ruminant calves (Kushibiki et al.4 3. only few reports have of retinol (a provitamin A).12 that whey protein has been reported to support net muscle mass gains with resistance exercise (Phillips et al.. 2006). Unlike casein-derived bioac. Moreover. Whey proteins Bovine Ovine Caprine Whey proteins can be consumed as ready-to-drink and Total whey proteins 5. 1). In addition. Typical concentrations of antimicrobial. Madureira et al. cheese) or by enzy. there is a growing interest focused on the short-term and long-term food intake regulation (Luhovyy nutritional properties of whey proteins and whey-derived et al. such as its role in developing pas- over. and it has been speculated that this protein may play This review will be focused on the most recent research a role in the absorption and subsequent metabolism of advances pertaining to the biological properties of ovine fatty acids. growth and development of specific organs. fatty acid binding focused on peptides released from ovine and caprine milk sites characterized on ␤-Lg allow this protein to partic- whey proteins.6–1. 2001). 1998. it has been shown that ␤-Lg enhances teins (see primary structure of ␤-Lg as an example.1.g. However. B.6 0..0 8. ence digestion. Fig. hydrolysis of these proteins can release fragments. Marked letters indicate differences between sequences. Hernández-Ledesma et al.. / Small Ruminant Research 101 (2011) 196–204 197 Fig. goat and other ruminants’ milk.8–2. Primary structure of ␤-Lg from cow. for this whey protein. Concentration (g/L) 2. 1.

Idota et al.. serum albumin’s inhibitory activity of breast cancer cells proliferation through modulation of autocrine growth reg- ulatory factors (Table 2). transports and supplies the tions of ␣-La in bovine.. HAMLET has broad antitumor activity in vitro. 2010).2.. Likewise. (1995a) Caseinomacropeptide Anti-cariogenic activity Oh et al. with its bovine counterpart. Laursen et al. its antioxidant activity has been reported ␤-Lg is widely recognized and has made this protein an to be effective on protecting lipids against phenolic induced ingredient of choice in the formulation of modern foods oxidation (Smith et al. (2001) Immunomodulatory activity Togawa et al. functional protein that binds. with values of approxi- ␣-La (Table 2). LF exerts its antimicrobial activity by two cells by a process resembling programmed cell death. 2006). (2002) Treatment of chronic stress-induced diseases Ganjam et al. (1995) ␣-Lactalbumin Lactose synthesis Markus et al. 2001). Concentra. (2010) Antiviral activity Van der Strate et al. Table 2). (1997) Anti-carcinogenic activity Hallgren et al. and its ther. (1992) Anti-carcinogenic activity Laursen et al. glioblastoma rat xenograft model. ␤-Lg is a rich source of Cys. 2002). et al. (1990) revealed and beverages (Chatterton et al.... 2010). (1995.125 mg/mL. Olakanimi et al. 1992). mately 0.. (2010) Growth and development Balan et al. an anticarcinogenic tripeptide produced by the Because of its size and structure. (1992) Transfer of passive immunity Sutton and Alston-Mills (2006) Immunomodulatory activity Wong et al. Hernández-Ledesma et al. (2000). The best known is the anti-tumoral activ. Protein Biological function Reference ␤-Lactoglobulin Carrier of retinol.. The high nutritional and functional value of 2002). (2004) Wong et al. (1998) Anti-carcinogenic activity Mcintosh et al. Moreover. (2007). different mechanisms. Mercier et al. (1998) demonstrated that this whey protein 2. (1992. The iron binding properties seem to Table 1. (2002) Anti-thrombotic activity Qian et al. (2002) Immunoglobulins Immunomodulatory activity Balan et al. (1984). in patients with skin LF also displays antiviral activity against both DNA. synthesis. Moreover. Both sheep and goat ␣-La possesses high homology vary between LF from different species (Sreedhara et al. 2008). (1994) Anti-thrombotic activity Manso et al. ity observed for the complex between human ␣-La and Traditionally it has been recognized to possess antimicro- oleic acid called HAMLET (human alpha-lactalbumin made bial and antifungal properties (Orsi. (2005) Immunomodulatory activity Wakabayashi et al. ovine and goat milk are included in organism with iron. Kawasaki et al. 2. / Small Ruminant Research 101 (2011) 196–204 Table 2 Biological functions of whey proteins. 1993) Immunomodulatory activity Otani and Monnai (1995).198 B.4. Some in vivo stud- lysosomal membrane permeabilization. also known as lactotransferrin. This complex is able to kill tumor 2002. (2008) Serum albumin Synthesis of lipids Choi et al. a complex of bovine ␣-La and oleic blocking cellular receptors or by direct binding to the virus acid (BAMLET) killed tumor cells via a mechanism involving particles (Van der Strate et al. .and papillomas and in patients with bladder cancer (Hallgren RNA-viruses preventing their entry in the host cell either by et al. an Serum albumin is a 582 amino acids-protein that essential amino acid that appears to stimulate glutathione appears in milk after its passive leakage from blood. 1995). Serum albumin stimulates normal murine spleen cells proliferation and Igs production. 1996) Prebiotic activity Azuma et al. is a globular multi- because of its requirements in lactose synthesis. 2004.. 2010). and it is physiologically important LF. serum albumin binds free liver for protection against intestinal tumors (Mcintosh fatty acids. (2002) Anti-proliferative activity Xu et al. Lactoferrin 14 kDa that consists of a single polypeptide chain with eight cysteine residues. ˛-Lactalbumin ␣-La is a small and globular protein of approximately 2. (2002) Antioxidant activity Smith et al. participating in synthesis of lipids (Choi et al. Otani et al. showing potent ies have shown that LF exerts a protective effect against cytotoxic activity against eight different cancer cell lines colitis in rats via modulation of the immune system and (Rammer et al. Recent research has revealed that bovine LF induced apeutic effect has been confirmed in vivo in a human apoptosis of human stomach cancer cells (Xu et al. lethal to tumor cells). The levels of this protein in sheep and goat milk are Some important bioactivities have been reported for slightly higher than in cow milk..1 mg/mL and 0. respectively (Table 1).. correction of cytokine imbalance (Togawa et al. (2009) Lactoperoxidase Antimicrobial activity de Wit and van Hooydonk (1996) Antiviral activity Shin et al.3. (1990) Lactoferrin Antimicrobial activity Orsi (2004) Antifungal activity Olakanimi et al. fatty acids and triglycerides Pérez et al.

Recently. 1998). cytokine production. Caseinomacropeptide C-terminal region f(113–135) of lactophorin. 2004). in recent years. and it is released by chymosin (or pepsin) cleav. 2004). immunomodulatory properties. until its own immune system is developed. intestinal as ␣-lactorphin. (1996) synthesized ing protection against diseases in the ruminant neonate three peptides from ␣-La with sequences YG. the cardiovascular effects of the tetrapeptide YGLF. Its unique amino acid composition makes it adequate for special 3. 1996). 1995a). In a study carried inmunomodulating and prebiotic activity (Mikkelsen et al... Igs constitute a complex group of globular pro.. (2006) used cheese microflora to pro- demonstrated that lactoperoxidase acts regulating expres.. ovine and caprine milk in the most active fraction (Table 3). Table 2). a ␤-Lg hydrolyzate was prepared 2006).. / Small Ruminant Research 101 (2011) 196–204 199 Finally. The biological properties of the CMP whey protein-derived peptides. 2002). which makes it a useful ingredient in During last years. B. and two potent ACE-inhibitory peptides were identified. was later tested in SHR and in normoten- and plasma Ig concentrations in growing rats (Balan et al. LLF and LQKW (Hernández-Ledesma et al. co-culture of Candida parapsilosis and Lactobacillus para- soluble fraction of milk whey. Antihypertensive peptides branched-chain amino acids (valine and isoleucine) and low in methionine. ferritin. such as phagocytosis.. 2005. duce several hydrolyzates of acid caprine whey with sion of genes involved in metabolism. This peptide. lysozyme. has been obtained after protein hydrolysis of caprine ␣-La activated lymphocyte proliferation through inhibition of (Bordenave. which provides protec.6. involvement of opioid receptors in its depressor action Lactoperoxidase is an important part of the natural (Nurminen et al. combined with lactoferrin in a cell culture. CMP is rich in 3. Chobert teins. YGLF and LF. The highest activity was obtained and cell cycle of epithelial intestinal cells (Wakabayashi after whey fermentation by the microflora from 18-months et al. Lactophorin is a minor casei.. 2000). 2004). 2006). associated with peptides derived from bovine milk. it has and their ACE-inhibitory activity was studied. This lial function. has been reported to display growth inhibitory CMP is composed by the 64 C-terminal amino acids of activity against both Gram-positive and Gram-negative ␬-casein. Angiotensin converting have received much attention in recent years (see review enzyme (ACE)-inhibitory properties have received spe- Thoma-Worringer et al. CMP also exerts tides (Recio et al. also been reported to have suppressive effects on mitogen. proteose-peptone. 2005). It has been demonstrated to have thrombin-induced platelet aggregation (Qian et al. The 2. apoptosis.. mucosa against pathogenic microorganisms. prolactin and folate-binding protein (Park et al. 2000). improving vascular relaxation in adult SHR enzyme. Despite none been demonstrated that oral administration of ovine serum of these peptides showed very strong inhibitory activity.. How- cesses (Manso and López-Fandiño. this ovine Ig fraction improving growth performance. Fractionation by RP-HPLC and amino acid analysis phosphoglycoprotein corresponding to component-3 of allowed the identification of the ␣-La fragment f(104–108) proteose-peptone found in bovine.. IFN-␥ production (Mercier et al. purified ovine LF and its pepsin hydrolyzate inhibit (Lister et al. ripened Comté cheese that was further characterized as a Proteose-peptone is defined as a heat-stable and acid.. ing heart rate in SHR and WKY with evidences for an 2009). Bioactive peptides derived from whey proteins diets. Shin et al. ␣-Lactorphin. 2007).. has in vitro (Sipola et al. Hernández-Ledesma et al. preventing the binding of different pathogens to cells on ACE-inhibitory and/or antihypertensive peptides are or the adhesion of bacteria implicated in cariogenic pro. Mullally et al. being effective on IgM pro- duction of hybridoma cells (Sugahara et al. and of yoghurts made protein).. been reported (Hernández-Ledesma et al. A recent study ever.. sheep and goat milk whey proteins has demonstrated the CMP’s protecting effect against acidic have become an important source of ACE-inhibitory pep- erosion of teeth (Setarehnejad et al. organ dose-dependently lowered blood pressure without affect- weight and gut morphology in growing rats (Balan et al. These authors 2007). sive Wistar Kyoto rats (WKY). Recent studies have Didelot et al. antihypertensive mechanism of this tetra-peptide showed tion against invading microorganisms and virus (de Wit that its beneficial effect was directed towards endothe- and van Hooydonk. the antihypertensive effect of these two peptides in spontaneously hypertensive rats (SHR) has Ovine and caprine milk whey contain minor pro. Table 3). also provid. immunity.. from ovine milk using different starters. called lac- tophoricin. CMP is able to interact with cial attention due their potential beneficial effects in toxins. bacteria (Campagna et al. On the other hand.. calmodulin (calcium binding ovine ␤-Lg hydrolysed with trypsin.1. 2010). (2005) investigated the ACE-inhibitory activity of lactoperoxidase. including Igs. out in our laboratory. have focused their studies on bioactivities associated with Salam et al. 2009. known lymphocyte proliferation. A more recent study . ACE-inhibitory activity. food scientists and technologists diets for patients suffering from hepatic diseases (Abd El. a peptide also 2010). Other proteins 2002). age of ␬-casein during cheese manufacturing. 2007). 2. the treatment of hypertension.. for instance in phenylketonuria patients’ diets since no phenylalanine is present. identified in this hydrolyzate several peptides responsible teins produced by B-lymphocytes that protects the gut for this activity (Table 3). Most published reports tion. viruses and bacteria due to its carbohydrate frac. et al. Subsequently. Further studies to shed light on the host defence system in mammals.. using thermolysin. transferrin. 1996. These authors had previously reported the effect of produced by enzymatic hydrolysis with pepsin and trypsin. Additionally.. Ig modulates aspects of immunity.5. ␣-lactorphin.

found that undigested bovine. / Small Ruminant Research 101 (2011) 196–204 Table 3 Sequence of bioactive peptides derived from ovine and caprine milk whey proteins. (1995b) CMP f(106–111)a . A contracting effect of this peptide demonstrated (Prioult et al..200 B. f(92–105). 2010). Antimicrobial and immunomodulatory peptides the activity observed in the ovine LF hydrolysate could be caused by other LF fragments (Recio and Visser.4 ␮M) thermolysin et al. 2003). Lg with pepsin and trypsin. b Goat milk proteins. b MAIPPKK ACE-inhibitory Tryptic hydrolysis Manso and López-Fandiño (2003) Lactoferrin f(14–42)b PEWSKCYQW Antibacterial Hydrolysis with pepsin Recio and Visser (2000) QRRMRKLGAP SITCVRRTSA ␣-La (104–108)b WLAHK ACE-inhibitory Cheese microflora Didelot et al. 2004). corresponding to fragment f(102–105) and lated from ␤-Lg enzymatic hydrolyzates has also been called ␤-lactorphin. Likewise. b MAIPPK ACE-inhibitory Tryptic hydrolysis Manso and López-Fandiño (2003) CMP f(106–112)a . These peptides positive and Gram-negative bacteria (Wakabayashi et al. ACE-inhibitory pep. or trypsin and chymotrypsin The immunomodulating potential of peptide fractions iso. but their digestion under sim. lactoferricin (LFcin). but it increased considerably after digestion under human LF f(1–47). identified. (1995b) CMP f(163–171)a TAQVTSTEV Antithrombotic Tryptic hydrolysis Qian et al. identified in the caprine LF hydrolysate (Table 3). 2000). the antimicrobial and immunostimulatory activities of ␤-Lg hydrolysed with different gastrointesti- nal proteinases have been examined by Biziulevicius et al. Peptide fragment Sequence Biological activity Produced by References ␤-Lg f(58–61)a LQKW ACE-inhibitory Hydrolysis with Hernández-Ledesma (3. f(84–91).2. and a homologous the potent antihypertensive tri-peptide IPP (IC50 value of peptide to LFcin. Only a peptic hydrolyzate of ovine ACE-inhibitory activity. and hence. 1992).3. have been purified and identified tides MAIPPK and MAIPPKK. and f(142–148) have been reported ␤-Lactorphin also improved the impaired vascular func- to stimulate murine splenocytes proliferation through the tion in mesenteric rings of adults SHR (Sipola et al. 2001). Recently. called respectively bovine and human simulated gastrointestinal conditions. although no peptides were identi. ␤-Lg has been found to be precursor of several opioid f(25–40). yielded YLLF. 1991). corresponding to fragment f(14–42). (2004) to inhibit the growth of Escherichia coli HB101. corresponding to ␬-CN (Bellamy et al. Hydrolysis of caprine and ovine LF by pepsin ulated gastrointestinal conditions allowed the release of resulted in antibacterial hydrolyzates.. Manso dose dependent manner. modulation of cytokine secretion (Jacquot et al. (1995b) CMP f(165–171)a QVTSTEV Antithrombotic Tryptic hydrolysis Qian et al.. (2005) CMP f(112–116)a KDQDK Antithrombotic Tryptic hydrolysis Qian et al. (2002. (2006) ␣-La (104–108)b YGLF ACE-inhibitory Hydrolysis with pepsin Bordenave (2000) (733 ␮M)c Antihypertensived a Ovine milk proteins. 2009). ulated guinea pig ileum in vitro (Antila et al. 2001). Proteolytic digestion of bovine ␤-Lg by trypsin allowed the release of four peptide fragments [f(15–20). (2005) ␤-Lg f(1–8)a IIVTQTMK ACE-inhibitory Tryptic hydrolysis Chobert et al. (2002. These peptides showed a potent f(106–111) and f(106–112) respectively. on smooth muscle has been determined in coaxially stim- responding to ␤-Lg fragments f(15–20). were identified antimicrobial activity against a wide range of Gram- from CMPs via proteolysis with trypsin. showed moderate activity. caprine and ovine CMP exhibited moderate ACE-inhibitory The antibacterial domains of bovine LF f(17–41) and activity. f(55–60). f(92–100)] with bactericidal activity peptides (Pihlanto-Leppälä.. fied (Hamme et al. peptides cor. Opioid peptides (2006). 3. Bacil- ACE-inhibitory peptides have also been identified in lus subtilis Cip5262 and Staphylococcus aureus 9973 in a hydrolyzates derived from ovine and caprine CMP.. also used microorganisms isolated from raw milk cheeses antibacterial and/or immunostimulating peptides from to produce several hydrolyzates of acid caprine whey with ovine and caprine ␤-Lg... but responsible peptides were not and López-Fandiño (2003). The region corresponding to the LFcin within the sequence of ovine LF was hydrolysed by the action of pepsin.. was 5 ␮M). a few data are reported about the release of lial function and also enhanced endothelium-independent . Hernández-Ledesma et al. c Studies carried out in the bovine peptide. f(78–83). f(139–148). 2007) Antihypertensive ␤-Lg f(103–105)a LLF ACE-inhibitory Hydrolysis with Hernández-Ledesma (82. Digestion of bovine ␤- against Gram-positive bacteria (Pellegrini et al. 3. This beneficial action was directed towards endothe- However.5 ␮M) thermolysin et al. ␣-La and ␤-Lg has been demonstrated by El-Zahar et al. 2007) Antihypertensive ␤-Lg f(142–148)a ALPMHIR ACE-inhibitory Tryptic hydrolysis Chobert et al. 2002).

B...4. the whey. Cu. Mg and Cl. et al. (1991). Ca. K. was slightly higher and Cl are almost entirely soluble and fully available in the (2. f(9–14).9% total minerals or ash. By fat-soluble vitamins are incorporated to the curd during using Caco-2 cell screening. / Small Ruminant Research 101 (2011) 196–204 201 relaxation. the ovine and caprine counterparts are gaining importance tides responsible of this activity were not identified. K. have resulted in the presence of multitude of whey prod- tent of 4. The most abundant elements are Ca. respec. reverse osmosis or ion exchange among others. The amount chymotrypsin digest of ␤-Lg by Yoshikawa et al. including ultrafiltration. compared to 0. and caprine CMPs and their hydrolyzates with trypsin and now the whey is seen as a potential source of bioactive were found to be inhibitors of human platelet aggregation components that can be used in the formulation of multiple (Manso et al. Fe. 2006. etc. with the sequence WYSLAMAASDI. 2009). Furthermore. these authors identified four cheese-making while water-soluble vitamins go mainly to kinds of novel peptide sequences which inhibited choles. 2007). due to the worldwide increase in the production of dairy products based on the milk of these animals. In this work. Sheep peptides with radical scavenging and lipid peroxida. claim their properties to growth or maintenance muscle cium. anti-stress and memory-enhancing 250–300 mg/mL. A posterior study of these authors provided the first Vitamins are physiological. i. milk (Park et al. proteins are especially important in terms of biological activity. whey powders. and Cu are higher in sheep than in cow proteases. For instance. P. has around 0. whey protein concentrates. However. and metabol- evidence that ␤-Lg tryptic hydrolyzate had hypocholes.. Lactose is the major carbohydrate in milk with a con. P. a general name for N-acetylneuraminic acid 2007).9 g/100 mL in sheep ucts in the market. and is richer than cow milk for most of the vitamins (Park VYVEELKPTPEGDLEILLQK. magnesium and phosphorous. Many of these oligosaccharides contain activities (Yamauchi et al. sialic acid. These peptides are also present has a significant drawback in folic acid and vitamin B12 in caprine and ovine ␤-Lg. it has been found that this peptide also (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). In the literature is described than sheep milk terol absorption in vitro. and Mn are the trace elements. goat milk f(41–60) of bovine ␤-Lg. cow milk. GLDIQK. TAQVTSTEV f(163–171) and QVTSTEV sheep cheese whey as source and precursor of bioactive f(165–171) that completely inhibited thrombin-induced compounds. which corresponded. among other effects. 2002).3. Mg. 2007). 1992). K. bovine. having high oxygen radical scavenging activity. Mg. Hernández-Ledesma et al. 20–30 mg/mL while in caprine milk is in the range of cholesterol-lowering.2. the infant’s brain among other positive effects (Park. Most of the terolemic activity in rats (Nagaoka et al. Goat most appropriate enzyme to produce ␤-Lg hydrolyzates milk contains about 134 mg of Ca and 121 mg of P/100 g. of oligosaccharides in ovine milk is in the range of It has a variety of actions including antinociceptive. The levels idant activity of hydrolyzates of ␤-Lg by commercial of Ca. ␤-Lactotensin (HIRL) is a peptide isolated from a possess prebiotic and anti-infective properties. Sialic suppresses food intake in mice after its oral administration acid present in milk seems to promote the development of (Hou et al... Although less explored than bovine whey. and less ical scavenging activity of one of the identified peptides. However. and the utilization mass. Among the dif- 4. The rad. On the other hand. from ovine CMP showed the strongest effect. goat and sheep milk have higher tively. IIAEK. Whey proteins have been reported to exhibit a greater hypocholesterolemic effect in comparison with casein or 4. (2005) investigated the antiox. Lactose and oligosaccharides processing technology. 2007). 2009). Final considerations Qian et al. P. 2001).e. are partly retained in the curd during cheese-making. microfil- tration. b. 3. there- (2. Overall.7% in tion inhibitory activities is receiving a special attention... Ohinata et al. and P are associated in different proportions by the synthetic antioxidant butylhydroxyanisole (BHA) to the colloidal suspension of casein micelles and. Minerals peptides Many major and trace minerals play an important role in In last few years. (1995b) hydrolysed ovine CMP with trypsin and identified three peptides with the sequences This review shows the remarkable potential of goat and KDQDK f(112–116). and amount of vitamin A than cow milk. where aspartic acid (D) is replaced by asparagine (N) in the caprine and ovine sequences. but the pep.4. Other biological activities of whey protein-derived 4. and Hernández-Ledesma et al. 4. the hydrolyzate obtained functional foods. Many of these products.62 ␮mol Trolox equiv. 1991. Vitamins soybean proteins in rats (Nagaoka et al. Recently. These authors found that Corolase PP was the milk. the searching for whey-derived the physiology and metabolism of the human body. ALPMH. Na. goat milk has more Ca. Other bioactive components in cheese whey ferent components of cheese whey. f(142–146). pro- nutrient because favours the intestinal absorption of cal. Na. Zn.1.43 ␮mol Trolox equiv. Zn. Fe.. biochemical. as happens with of vitamin C. to fragments f(71–75).1 g/100 mL in goat milk and 4. Mg. the opposite appears to be the case of K and Na. The traditional view of cheese whey as a by- human platelet aggregation. ical bioactive compounds occurring in milk. 2009). fore. This disaccharide is a valuable reduced lactose whey./␮mol peptide) than that shown whey. The advances in 4.. ovine product of dairy industry with little value has disappeared. except for the longest sequence compared to cow milk (Park. milk oligosaccharides other claimed activities for whey proteins including their . Na and S contents than cow milk (Park et al. 2003a./␮mol BHA).

73. J... El-Zahar. Mattila.. and gut morphology in growing rats. O. Mer.... J.2010. C. S. Ohinata. B. Preparation Biol. Com. ElShibiny.A. J. P.J. 215–229.M. A. Preparation of angiotensin-I-converting acceptance from EFSA. Biziulevicius. Prepa- References ration of antioxidant enzymatic hydrolyzates from ␣-lactalbumin and ␤-lactoglobulin. Shinmoto. AGL2008-01713. followed by the CGRP system in mice. Amigo.M.. Bordenave-Jurechereau.. S. Agric. focused on well-designed clinical trials to confirm the 976–983. 2004.. H. Metro. 805–812. K.. Qin. Miguel.. M. Mäntsälä. organ weights.. Université de la Rochelle. Ho.. Apoptosis and tumor cell death in response to HAMLET Acknowledgments (human alpha-lactalbumin made lethal to tumor cells). ACOSC–Associacão dos Criadores de Ovinos e Caprinos do Sertão do pared to whey proteins more research on bioavailability. Hernández-Ledesma. Int.. R. AGL2007-65035. L. 53. Recently. 606. Amino Acids 35. M.. 2000. Identification of peptides by HPLC–MS/MS. B. Hernández-Ledesma et al. Gaillard. 2000. S... M.... Biotechnol. Curry. Abd El-Salam. Characteristics and Food Chem.. 2007. K. A. stances. Bioactivity existing ones were inappropriately done (European Food of ␤-lactoglobulin and ␣-lactalbumin—technological implications for Safety Authority...M. S. Biosci. Amigo. B. J... 20.K. D. K. van Hooydonk. L. Med. 2325–2339. Sannier. L.. 19–44. 6.. Bartolomé. 2008. human studies document. K.. Marshall. Nutr.-L.H... Safety Authority (EFSA) delivered a scientific opinion on Campagna.H.P.2903/j. 2010.. Correia. McSweeney. 50. different health claims related to whey protein under Reg. Biotechnol. P. / Small Ruminant Research 101 (2011) 196–204 effect on satiation and satiety. Choiset. 217–240.. Rutherfurd. M... S. 257–265. M. Sitohy. Fruitier-Arnaudin. J. Recio. Mossberg. on murine splenocytes... V. Conflict of interest statement European Food Safety Authority. Takase. K.-G.. 1984. Cogan. Chobert. M. 2008... 1720–1722. whey”. 2009. M. 1997. B.A. I. 1702–1710. 57. bovine beta-lactoglobulin suppresses food intake via the CRF system Balan. Orally Identification of active peptides from ␤-Lg hydrolysed with ther- administered ovine serum immunoglobulins influence growth perfor. Mitsuoka. T. 2006. Agric.P. Kawakami. from in-vitro proteolysis of bovine whey proteins. M.. Appl. 2010. Y. F. Biol. Dairy J. ality. H.. Didelot.S. Moughan.W... ␤-Lactoglobulin as Azuma. Dairy Res. Dairy Res. M... Singh. Hernández-Ledesma. Hamilton.. S. and Lactobacillus rhamnosus: contribution to proteolysis and ACE inhibitory activity. J. Dalgalarrondo. EFSA J.. Int.. G.. Int.. Chromatogr. S. Milchwissenschaft 59. However.. Drouin. MacDonald.H... T. the recent interest has mainly Choiset. S. Hou. Buchheim. Hallgren. Aspen Pub- cedes Ramos and José Ángel Gómez-Ruiz) has a financial or lishers. 131–138.. Hahn. Antiproliferative effects of yoghurt fractions obtained by membrane tled “Bioactive components of ovine and caprine cheese dialysis on cultured mammalian intestinal cells. Isoda. Schaupp. 155 pp. Tomita. Balan. Med. J. 2005. Pihlanto.... 1214–1215. B. Yoshikawa. 74. Effect of simulated gastrointestinal digestion on the anti- Leppälä.. Biochem.. Lait 85. Antimicrobial activity of ovine whey protein and their peptic hydrolysates. 327–341. L. Moughan. 1924/2006. Wullt. R. Structure. I. Proliferative effects tide derived from the N-terminal region of bovine lactoferrin. L. functions and applica- tive peptides.. M. Didelot. 80. actions of very long-chain saturated fatty acids with serum albumin. 152–157. I. A.M. P..K. 653–656. Consolider Ingenio A 795. 472–479. El-Zahar. Adv. 1998. Antila. W. Crude goat whey fermentation by Kluyveromyces marxianus B. S.F. Chemistry of milk constituents. J. Svan- borg. Kislukhina. I. B. A. 2004. 16. stand out some activities like antihypertensive.. 1992. ties of the intact proteins. Biosci.. D. Food-protein enzymatic hydrolysates possess both antimicrobial and T. that could inappropriately influence or bias the paper enti. a potent bactericidal pep. K. 2010. lactoferrin of influenza virus hemmaglutination. 1229–1240. Yamauchi. Apart from the biological activi. Dairy J. I. 8 (10). the European Food teur à ultrafiltration: génération et caractérisation de peptides issus de lı̌hydrolyse pepsique. 2005. 16. These studies should be especially enzyme inhibitory hydrolysates from unsupplemented caprine whey fermentation by various cheese microflora. J.. 336–339. Int. J. P. Girardet. M.N. Opioid peptides derived hypertensive properties of ␤-lactoglobulin peptides.1818 (28 pp.H. Kawase. 1818. beta-Lactotensin derived from 139. P. 1994. Leite de cabra e derivados.. Y.. Rosenfeld. Fleury. A. Bulletin. Kazlauskaite..H.. F. Haertle.efsa. Bordenave-Juchereau.V.. Immunomodulatory effects of ovine serum immunoglobulin in Idota. A. 43. W. Idota. personal relationship with other people or organizations Ganjam. Bifidobacterium growth the growing rat. Nakajima. N. R. Among Choi.F. 2159–2162. Aits. A. 58. P... Peptides 30. Metro. 46.... toxicity and animal studies have been carried out for bioac. opioid. Y.202 B.. Nakajima. R. M..T. Thornton. Sitohy.-L.L. Han. S.. In: Fundamentals of Cheese Science. Boutin. Kawasaki. T. 2009..M. 2006. P.. Recio. of synthetic peptides from beta-lactoglobulin and alpha-lactalbumin Bacteriol.. Järvinen. 87. Lipid Res. Jacquot. Bifidus growth promoting source of bioactive peptides.. Antibacterial activity of lactophoricin. T. Tanimoto.. C. 1. R. Y. S. K. Dairy Sci. P. 1996. based on the absence of human studies or because the Chatterton. 2010 FUN-C-Food CSD2007-00063 and P2009/AGR-1469. Bordenave. Bittman. Microbiol.. Y. de Wit. T. 1993.. Schulz. potential health effects of these products. P.). matic hydrolysis and/or fermentation processes.. Mathot. Fox. Amigo. 2002. Paakari.. and of milk yoghurts obtained by using different starters. Dairy J. I. K.. Hellman. mance. R. Ramos. Inhibition by k-casein glycomacropeptide and immunostimulatory activities: a cause and effect theory of bifunction. L. FEMS Immunol.. Dairy Sci.. Hamme.. Brest. Int. Han.... F. F. Recio.C.J. P. 2006. protein-based products and those containing whey bioac.. Bovine whey frac- This work has received financial support from projects tionation based on cation-exchange chromatography. Haertle.. Amigo. 2010). antioxidant... Cruz.S. Dosako. such as enzy... H. A.M. Thèse. M. tive peptides are required in order to gain the official Piot. Hernández-Ledesma. A. 2006. doi:10.. Wakabayashi. J... J. J. Aleixandre.. 1621–1626... 2002. Exp. Roupas. Guinee.. J. 1996.F. Gauthier. P.. Dairy J.S. Piot.. Cabugi. promoting activity effect of N-acetylneuraminic acid containing sub- Bellamy. Angiotensin I-converting-enzyme (ACE)- focused on bioactive peptides encrypted within the whey inhibitory activity of tryptic peptides of ovine beta-lactoglobulin proteins that are released by different means..T.. Neth. of ovine and caprine ␤-Lg hydrolysates with ACE-inhibitory activity. Brodkorb. Gustafsson. O.. Animal 4... Jungbauer. H. potential uses of the casein macropeptide. J.. antimicrobial and hypocholesterolemic. Sannier. Health claims were rejected derived from the sequence of Bovine Milk Component-3 of proteose peptone. I. J. Hydrolyse de lálpha-lactalbumine caprine en reac- ing these benefits are limited. H. T. J. 277–287. additional studies in both whey tions of lactoperoxidase in natural antimicrobial systems. 76. activity of a glycomacropeptide derived from human k-casein.. H. J. Inter- the plethora of bioactivities described for these peptides. W. Antibacterial spectrum of lactoferricin B. Dairy J. J..M... 48.. Smithers. a synthetic 23-residues peptide ulation (EC) No. 514–521. molysin. Rutherfurd-Markwick. Singh.E... Dairy J. pp. Chem. 12. Milk Dairy J.C. thanks CSIC for her post-doctoral research contract. Dávalos.S... Laukkanen.. E. J.. Gaithersburg. 2228–2232..J. Int. I. None of the authors (Blanca Hernández-Ledesma... 2009. 1000–1010. MD.M. G. V. 588–593. Zukaite. Chobert. V. Biochem. processing.-M..A. . J. 141–152. 244–249. 227–244. 1991. K. Hernández-Ledesma.

M.L. Kuzuya. and caprine kappa. López-Fandiño. 1484–1485. enhances memory consolidation in mice. 50. R. Smithers. Wiley- 2111–2115. Bioactive peptides derived from bovine whey cheese whey: physicochemical. Biotechnol. In: Park. 259–260..A. A.. Kurokawa. H.E.. and glycosylation of component PP3 Park. A... Bioactive com- Dairy proteins protect against dimethylhydrazine-induced intestinal ponents in sheep milk.E.. Isolation Mikkelsen. 1535–1543.. Ltd. Ena.. phosphorylation..M. S.K. A.. H..S. Wiley-Blackwell. 1470–1474. K. ovine and caprine lactoferrins: a comparative study.. receptor expression on mouse CD4+ T cells by bovine k- ing of Cholera toxin to its receptor.S. Whey proteins in the Park. In: Park. Dairy Sci. Kanekanian. Diagn. 2009... 2007. Nutr. Am. program in cancer cells. lactoferrin and lactoperoxidase on influenza virus infection in mice. Y. 83–104. M. acid sequence.. Kirkegaard. L. Ramos.. De la Fuente. Biophys. 88–113. 66. Invited review: physiological properties of bioactive peptides and characterization of four bactericidal domains in the bovine ␤- obtained from whey proteins.. Z. N.. K. Biochim.. 2004... 2004. G.. tor antagonist-like component produced from mouse spleen cells Shinoda. J.. Ghodke. Tossavainen.. 20.. A..W.B..... Kawasaki. Int. Teraguchi.E.. G.. B. A. I. Dairy Sci. Calvo.W. 2007. 2005. / Small Ruminant Research 101 (2011) 196–204 203 Kawasaki.. Kappa-casein macropeptides from Pihlanto-Leppälä.R. 2007. Acta 1244. Luhovyy. pp. 717–723. 1983. 1992. M. Nutr. K... Rheem. 56. 2003. 597–605. perspectives. Bioactive components in goat milk. A. J. P.. 349–357.J. Res. characteristics of goat and sheep milk.. K.M. Moore. Food Rev.. J.. S.. Food Prot. nutritional. Dairy Sci. Inoue. Biochim. Juárez.M. 11. Migliore-Samour. Y. Tadashi. Biochem. R. 1686–1692.and soy- enzyme—inhibitory activity of bovine. The primary structure of caprine PP3: amino cheeses and yoghurt. Sánchez.). Korpela. 329–355. Kaul. Y. Mullally. Biometals 17. 93. 20. S. L. M. ␣-Lactorphin and ␤-lactorphin Oh. Identification of novel hypocholestero. Publication. Anticancer cytes by bovine k-caseinoglycopeptides having different carbohydrate Res. Biotechnol. Nutr. Pintado.J. J.. 56. T... Paccard. M.. an inhibitor of platelet- Immunogenicity of kappa-casein and glycomacropeptide. Lab..W. Regester. G. Halliwell. with angiotensin-I-converting enzyme inhibitory activity. 809–816. 281. 285–384. M. Fliss.. Biophys. Ohinata. Life Sci. Biochem.. R.. and caprine kappa. Tanimoto. A.. 2001.. Inhibition of mitogen-induced proliferative responses of lympho- tor on growth of the human breast cancer cell line. B.. Lister. C. Finckenberg. J. S. ovine... 2010. protein accretion in young and elderly persons... Prakash.D.L... K. D. 1990.. Chem. 131–140.H. 579–586.. M. 516–522..M. Wiley-Blackwell/John Wiley & Sons. T. 68. Monnai. Fiat... Life Sci.. Huth. 59. Platelet Pérez. Horimoto.F. P. J.. 2010. Stokes. H. ical features for possible uses. 2006. C. Britigan.. Prioult.. Vegarud. 1992–1996. Szyniarowski. A. Int. V. J. Daugaard... MCF-7. A. Agric.P. Coll. (Eds.E.. Alijo. Vapaatalo. Kanamaru.J. Lagriffoul. S. O. P. Dairy Res. Jollès. Kemp.K. Oria. Y. Pihlanto-Leppälä. Otani. F.. Nurminen. 2002. Beta-lactotensin.. Petersen.-L. role for this protein in ruminant milk. J... Food Prot..M. Tanimoto. I. pH and thermal stabilities of Peptides 28. Biosci. Effect of beta-lactoglobulin on plasma retinol and by bovine k-caseinoglycopeptide. Kim. O. laemic peptides derived from bovine milk ␤-lactoglobulin. Idota. J..E. USA. R. B. Akhavan. Fliss.. P. Manso. from the proteose-peptone fraction of caprine milk. Worobo. Yoshikawa.S. G. Induction of an interleukin-1 recep- Kushibiki. 2009. K. 79. M. Acta 1526. H. Olakanimi. M. Korhonen. T. Kuwata. L.E. G.. Piilola... Juárez. 2010. Chilliard. Acta 1243. M. M. 64. Nagaoka. Guillet. Dosako. Res. P. Am. Yamauchi.. The antimicrobial activity of lactoferrin: current status and from different breeds and species of ruminants. Isoda. C.H. R.. Anderson.. G.. J. Rammer. Kurisaki... 1998. A. Yamauchi. J. T. Biochim... tective effect of caseinomacropeptide against dental erosion using Comparative-studies on the serum-cholesterol lowering action hydroxyapatite as a model system. its production by the response surface methodology.E...M. K. 189–196. J. M. 1166–1168. M. Futamura. Aranda. I. 437–455. and characterization of sheep lactoferrin. Miwa. E. Int.. 483–489. of whey-protein and soybean-protein in rats. J. Sheep kappa-casein peptides inhibit platelet-aggregation. R... and fatty acid composition in calves. Hunziker.D. The pro- Nagaoka. 2008. Kuwata.. P. proteins: opioid and ace-inhibitory peptides. Effects of whey-protein and bovine. Y. A. Whey Processing.. Frokiaer. of beta-lactoglobulin on the activity of pregastric lipase a possible casein macropeptides and their tryptic hydrolysates.. 1992.. Rasmussen. Kanamaru.. E. Shiraki. ality and Health Benefits. P. 57–72. J. 1996. T. J. T.. Small Rumin. Kuzuya. 2000. U. Biochem. Res.. Otani. in stress-vulnerable subjects. 704S–712S. 2076–2084. J. Serum-albumin as a modula. de Haan. R. Dairy Res. T. Escudero. Storry. 11. Y. Clin. Meisel. R. N. T. Biophys. Ahiko.. Yamauchi. S. Vapaatalo.. Whey proteins and peptides in human Qian.R.Y.F.. M. Blackwell/John Wiley & Sons.W. S. Abedi. Stimulation of interleukin-10 pro- lactalbumin increases the ratio of plasma tryptophan to the sum of the duction by acidic beta-lactoglobulin-derived peptides hydrolyzed other large neutral amino acids and improves cognitive performance with Lactobacillus paracasei NCC2461 peptidases. B.B. 9.. Immunol. Lykkesfeldt. Function. 54. Wakabayashi. A. 343–354.. 1017–1019. B. 11–17. Sipola. 1995. K.H. Food Chem. 2001. 824–830. biological. 28.. Y. Sonoda.I... Møller.. Med. 2008. R. H. Bioactive Components cancers in rats. L. Visser. Kawakami.. M. M.E. 30.. Structural characteristic... Malcata. J... J. pp. E. A. Rasmussen. Shingu. Recio. 1995.. 1992. 2002.. Res. Grandison.. whey proteins and their enzymatic digests.. Owen. Langsrud. M. Tavares. Acta 1123. Dairy Res. T. Nutr. Kaarto. 2001.).. Pellegrini..X. 2000. Lelue. Effect aggregation inhibitory activity of bovine. 66. 1159–1170. Mcintosh.. 2002.. Y.. Fiat. D. apo and holo forms of caprine and bovine lactoferrins.E. responding to alpha-lactalbumin and beta-lactoglobulin sequences A. 81.W. P.J.. 1245–1253. 175–183. 343–351. Int. a neurotensin agonist peptide derived from Sreedhara. 1996. R. Barkholt. Gauthier.K. ovine.. Biochim. Y. Schoentgen. Jäättelä. Setarehnejad.. Tatham. Royle. Y. chains.. 813–818.. Cancer Ther. Shin... IA. J. Small Rumin. Gomes. Johnsen. 10. T. Mercier. Chem. G... Biosci. Am. Otani.... 89.. Dairy J. caseinoglycopeptide. Ltd.. Manso. Povlsen. A. Biotech. Kim.. 25–32. Høyer-Hansen.. 14. Coll. A. (Ed. Pihlanto-Leppälä. V.M. 60. Watanabe. 195–198. ␣-Lactorphin low. Whey protein rich in ␣. M. A. 215–229. Lewis. Biochem.A. Ramos. K. BAMLET activates a lysosomal cell death Hoppe-Seyler 377... H. Nylandsted. H.. 1051–1056. T.. 65. Biophys. 1992. H. K. Biometals 23. H. Olivier. R. Millard. Y.. Biol. Synthetic peptides cor.. 55. Y. Monnai. Larsen.. 68.. Thomas.. Smith.. M. Laursen. 1995b. 2007.. Effects of orally administered bovine Nurminen. Suppression of interleukin-2 Inhibition by lactoferrin and k-casein glycomacropeptide of bind. Hernández-Ledesma et al. R. Wada. Immunol. Madureira. Biochem. Small Rumin. Chemical composition and coagulating properties of renneted milks Orsi. López-Fandiño. P.. Qian. A. Aruoma. I. Biosci. J. S. Briand.. In: Onwulata. M. P. Rasmussen. M. J. 2004. 652–656.. G... (Ed.A. S.Y. rin and lactoferrin by myeloid cells.. B. Dettling. Commun. S. 1991.. P. L. Multivalent metal-induced iron acquisition from transfer.. Clin. López-Fandiño. M... C.A. Groth-Pedersen. H. lactoglobulin. H. 151–155. I. Monnai. 75.. Isolation 2010. P. Y.). Z. Ford. FitzGerald. 10.. Pandya. M. Manso. Toxicol.H. S. Haenlein.. G. M.. Biochem. S. Biotechnol. M. Mol. Flengsrud.M.. Y. Rytter. and technolog.. A.. A. Biophys. Olsen. S.. Angiotensin I converting Phillips. 1995. Y.. Hodate. toxin-binding activity of k-casein macropeptide and optimization of 71..D. 125. J. pp. 411–417. Bioactive Components in Milk and Dairy Products. Biol. 2001... M.R. 193–206. T. Physico-chemical regulation of food intake and satiety.-L...J.... H. Jollès. Composition of goat and sheep milk products: an update. 26. K. Dairy J.. ers blood pressure measured by radiotelemetry in normotensive and Sipola. 62. the prooxidant actions of phenolic dietary-components. L.. triglyceride concentrations.. Raynal-Ljutovaca. . L.. Ueda. Fitzgerald.T. A. 68.. bovine beta-lactoglobulin. Technol. Migliore-Samour. Protection by albumin against nol.. 2004.W. C. A.J. M. health. G. M. 24–32.. D. 43–81. Morris.. based protein in support of muscle protein synthesis and muscle casein macropeptides and their tryptic hydrolysates.. K. Kanamaru.D. Awano. H... 169. Tamura. 2009. K. Tang... Microbiol. Kojima. Dairy casein on the plasma and liver lipids in rats. 1995a.. Detection of cholera improve arterial function in spontaneously hypertensive rats. spontaneously hypertensive rats. I. O. The role of milk. Antibacterial and binding characteristics of Nagaoka. Trends Food Sci. 2002. Pecquet. Recio. Markus.I. P. Biosci.. 266–271. Goat and sheep milk products other than Sørensen.W... Korpela. J. Y.. Immunomodulating effects of Publication. 2000. Biotechnol. 347–356... Biosci. D.. in Milk and Dairy Products. F. aggregation and comparison with human lactoferrin..

. Dairy Sci. 2003b. 601–608. of stomach cancer cell SGC-7901 and regulation of Akt signaling way Thoma-Worringer. H. Harmsen. Orally administered lactoperoxidase increases Effect of ␤-lactotensin on acute stress and fear memory. A Discov. 93. small intestine of mice: a DNA microarray study. Takase. M.R. 2005..K.. Molema. ␤-Lactotensin and neu- A. Nagase. H.. R. 187–195. Yamauchi.. Akiyama. Mol. Q.... Saito. Sato.. 1277–1287. 1825–1832. Xu. B.. Dey. 1998.. M. Wakabayashi. Immu- lymphocytes. M. Shin. Emerging therapeutic potential of whey proteins and 1324–1333.. as a neurotensin agonist. Alston-Mills.. R.. Biochim. M. M. B. Biophys. 225–239. R. D. Wakabayashi. and technological features of caseinomacropeptide. J. Health effects induced by bovine lactoferrin. 52. Des. Cell. L. H. 2006.. 2006.. Onda. T.. S.. 16. M.. H.. 2003a... 9. Yoshikawa. J. Li. Jiang. M.. Tani.. Zhou. H. R. Antiviral activities of lactoferrin. Apoptosis Rec... Evol. M.. R. Physiol. Lactoferrin reduces rotensin rapidly reduce serum cholesterol via NT2 receptor. R. 283. Abe.F. 288.. Matsumoto. from bovine ␤-lactoglobulin. K. Pharm. 2010. Y. Dairy J. peptides. Yamauchi. nol..I.. Antiviral Res. T. Y.. Usui... Middleton. Inamori. bovine milk protein fractions. H. a bioactive peptide derived Van der Strate.. Hara. 81. Sorensen. 2006. Wada. Miyauchi. M. Zhang.... Acta 1725. 2006. K. M. Tanaka. Curr... Horii. Biosci. Shinohara. Sekihara. 67. Gastrointest.. T. I.. Biochem. 71. E. Characterization of ␤-lactotensin... 2002. Takase.. Togawa. Japan Kokai Tokkyo Biochem.. component 3 fragment on human hybridomas and peripheral blood Wong. López-Fandiño. Liver Physiol. H. J. H.. Anat. Pharm. F. Lactoferricin derived from K. K. 2344–2350. Biol. Yamauchi. Curr.. 1955–1961. H. Yoshikawa.C. 2003. Yoshikawa. N. Montgomery. L. nostimulation of murine spleen cells by materials associated with Sutton. T... 220197 (Sep. Koho. Chiba. 12.. 2007.. Nakajima. M. K. Meijer.. F. H. 2274–2282. Hernández-Ledesma et al.... Biotechnol. Naito. Ohinata. Beljaars. Nakamoto. G. K. / Small Ruminant Research 101 (2011) 196–204 Sugahara. Yamauchi. 233–240. 940–943. 1991. Peptides 27. expression of the FK506 binding protein 5 gene in epithelial cells of the 3176–3182. C. Yoshikawa.. Tani. Biotech- 2001.X. Takenaka. M. . Wada. Biosci. Yalcin.. K. Dairy Sci. Des... Sasaki. Tomita... D. Umezawa. M. X.B. Yunden. of cytokine imbalance. 27). K. K. J. J.204 B.N.. Yamada. Int. K. Immunostimulation effects of proteose-peptone milk protein lactoferrin. Beta-lactoglobulin as a potential mod. Liu. Am.. Carr... 1637–1643. J. ulator of intestinal activity and morphology in neonatal piglets.. A. Peptides colitis in rats via modulation of the immune system and correction 24. N.S.W..F.