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Lactoferrin As a Nutraceutical Protein from Milk, an Overview

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Lactoferrin As a Nutraceutical Protein from Milk, an Overview International Dairy Journal 89 (2019) 37e41 Contents lists available at ScienceDirect International Dairy Journal journal homepage: www.elsevier.com/locate/idairyj Review Lactoferrin as a nutraceutical protein from milk, an overview Blanca F. Iglesias-Figueroa, Edward A. Espinoza-Sanchez, Tania S. Siqueiros-Cendon, * Quintín Rascon-Cruz Laboratorio de Biotecnología I, Facultad de Ciencias Químicas, Universidad Autonoma de Chihuahua, Circuito Universitarios s/n Nuevo Campus Universitario, C. P. 31125, Chihuahua, Mexico article info abstract Article history: Lactoferrin, a non-haeme iron-binding glycoprotein, known as the red fraction of milk, has been recently Received 11 May 2018 called a nutraceutical protein. Lactoferrin protein participates in some immunological processes and has Received in revised form an antimicrobial response against a broad spectrum of pathogens: it is also proposed to play a role in 12 September 2018 mechanisms of both neurodevelopment and neuropathy, and recently, the impact of lactoferrin against Accepted 14 September 2018 the metabolic syndrome was suggested. Other properties like anticancer, antioxidant and enzymatic Available online 11 October 2018 activity have been reported. Because of this, the potential use of lactoferrin as a nutraceutical in the food industry makes it especially attractive to study and characterise. This review focuses on the description of lactoferrin as an important nutraceutical in science and food industry. © 2018 Elsevier Ltd. All rights reserved. Contents 1. Introduction . ................................................. 37 2. Lactoferrin characteristics . ................................................. 38 3. The role of lactoferrin in the immune system . .................................... 38 4. Antimicrobial activity of lactoferrin . ............................................ 39 5. Lactoferrin in neurodevelopment and neuronal diseases . .................................... 39 6. Lactoferrin implication in metabolic disorders . .................................... 39 7. Other physiological implications of lactoferrin . .................................... 39 8. Future considerations . ................................................. 39 9. Concluding remarks . ................................................. 39 Acknowledgements . ........................40 References................................................................. ................................ ........................40 1. Introduction polyunsaturated fatty acids, minerals, antioxidants, dietary fibre and proteins, glycopeptides and amino acids (Andlauer & Fürst, The term “nutraceutical” dates almost 30 years ago. Stephen 2002; Espín, García-Conesa, & Tomas-Barber an, 2007; Kalra, 2003). DeFelice (Foundation for Innovation in Medicine, New York, US), Dietary components may play beneficial roles above nutrition, coined this word to include all the food and/or their chemical driving to the development of the functional food concept and components, that provide a health benefit to the consumer. nutraceuticals (Cencic & Chingwaru, 2010). The proteins present in Nutraceuticals are currently classified within the nutritional sup- food, as well as being an important primary nutrition component, plements containing active ingredients in concentrations greater are a source of bioactive peptides with functions that can promote than those found naturally in foods. Examples include: health and prevent disease (de Mejia & Dia, 2010). Currently, the consumption of food with nutraceutical properties has increased in the world. Foods like milk, chia seeds (Salvia hispanica L.), soybean * Corresponding author. Tel.: þ521 614 23606000. (Glycine max), canary seeds (Phalaris canariensis L), among others, E-mail addresses: [email protected], [email protected] (Q. Rascon-Cruz). have been described by their high nutraceutical content; however, https://doi.org/10.1016/j.idairyj.2018.09.004 0958-6946/© 2018 Elsevier Ltd. All rights reserved. 38 B.F. Iglesias-Figueroa et al. / International Dairy Journal 89 (2019) 37e41 the availability of these last two is limited to regions of the world 3. The role of lactoferrin in the immune system due to climatic conditions necessary for its production (Pandey et al., 2016; Sandoval-Oliveros & Paredes-Lopez, 2012; Valverde, Since the discovery (Sorensen & Sorensen, 1940), and subse- Orona-Tamayo, Nieto-Rendon, & Paredes-Lopez, 2017; Wada & quent characterisation of lactoferrin (Groves, 1960), many proper- Lonnerdal,€ 2014). ties of this protein have been documented. The role that this Milk is one of the most consumed foods in the world; it is an molecule plays during the immune response has been extensively excellent source of nutritional content and contains all the nutri- studied and is one of the main features that have made it extremely ents needed for the healthy development of infants (Lonnerdal,€ attractive to both the pharmaceutical industry and research. 2013). There are several reasons causes why breastfeeding is not Lactoferrin is strongly involved in immunological processes an option for mothers at times, so the use of infant formulas is response to pathogens, as well as inflammatory disorders, common practice for the development of the newborn (Figueroa- including allergy, arthritis, and cancer (Legrand et al., 2008). In Lozano, Valk-Weeber, van Leeuwen, Dijkhuizen, & de Vos, 2018). response to an inflammatory and/or neurodegenerative process, In this respect, Lactoferrin (Lf), identified in milk in 1939 (Sorensen secretion levels of Lf increase significantly (Zucca et al., 2017); Lf & Sorensen, 1940), has a wide spectrum of functions and currently can mediate the actions of the innate and adaptive immune re- is recognised as a nutraceutical protein. Currently, multiple activ- sponses (Siqueiros-Cendon et al., 2014). Although the molecular ities, such as immunomodulator (Siqueiros-Cendon et al., 2014), mechanisms of immunomodulatory action have not been fully antimicrobial (Legrand & Mazurier, 2010), antioxidant (Kruzel et al., understood, it is known that Lf can regulate the production of in- 2013), anticancer (Tsuda et al., 2010) have been ascribed to lacto- flammatory mediators both up and downwards (Giansanti, Panella, ferrin, and recently its roll in metabolic disorders as obesity, dia- Leboffe, & Antonini, 2016). betes and cardiovascular diseases has been described (Mayeur, Several authors have suggested that a fundamental part of the Spahis, Pouliot, & Levy, 2016). In the present review, we will immunomodulatory mechanism of action of Lf is related with the describe the most important properties of Lf and its potential use as glycosylation of the molecule. The degree of Lf glycosylation could nutraceutical and also perspectives on infant nutrition. affect its ability to modulate the immune response (Choi et al., 2008; Zimecki, Artym, Kocie˛ba, Duk, & Kruzel, 2014); in this 2. Lactoferrin characteristics context, three potential glycosylation sites have been reported in human lactoferrin (hLf) (Asn138, Asn479, and Asn624; Spik et al., Lactoferrin is a ubiquitous glycoprotein of mammals. It has a 1994) and five potential sites in bovine lactoferrin (bLf) (Asn233, molecular mass of approximately 80 kDa, and its structure is formed Asn281, Asn368, Asn476 and Asn545; Wei, Nishimura, & Yoshida, by two symmetrical lobes (N-lobe and C-lobe) connected with a a- 2000). These sites are mostly exposed on the external surface of helix. The simple polypeptide chain includes approximately 700 the molecule and are involved in recognition of certain cell re- amino acids, according to the species; however, there is a high ho- ceptors of the immune system (Latorre, Puddu, Valenti, & Gessani, mology among species. Lf presents high affinity for iron; each lobe 2010). In vivo and in vitro studies have shown that expression levels þ þ þ can bind one ferric ion; moreover, it can bind Cu 2,Zn 2 and Mn 2 of inflammatory cytokines like IL-4 and IL-10, pro-inflammatory ions (Adlerova, Bartoskova, & Faldyna, 2008; García-Montoya, cytokines like TNF-a, IL-1, IL-6 and IL-12, as well as chemokines as Cendon, Arevalo-Gallegos, & Rascon-Cruz, 2012). The highest IL-8, are altered in the presence of lactoferrin, which affects the levels of lactoferrin production are attributed to milk and colostrum natural processes of growth, differentiation, and activation of im- À À (1 g L 1 and 7 g L 1, respectively); the latter has a significant impact mune cells (Legrand, 2016). An interesting feature of the immu- in the proportion of essential components in the immune system of nomodulatory effect of Lf, is the fact that is not only limited to the infants (Moreno-Exposito et al., 2018). Moreover, lactoferrin is alteration in the expression levels of cells: its ability to chelate iron secreted by several body fluids as seminal and vaginal fluids, tears ions, enables lactoferrin to act as a natural antioxidant (Sharma, and saliva; it is present in neutrophils at a concentration of Chakraborty, & Gupta, 2015); also, Lf prevents peroxidation À approximately 0.4 mg L 1 in human plasma under normal condi- caused by free radicals (Yuksel, Yigit, Cinar, Atmaca, & Onaran, tions, increasing up to 5000-fold in the infection process (Embleton, 2015). Table 1 summarises the most significant effects of Lf as an Berrington, McGuire, Stewart, & Cummings, 2013). immunomodulator that have been reported in recent years. Table 1 Cell-based studies demonstrating immune responses mediated by lactoferrin. Source Effect Model Reference
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