Progress in Skin Care Efficacy of Lactoferrin

doi:10.21127/yaoyimr20210015

Abstract

Abstract: Lactoferrin is an iron-binding glycoprotein with a variety of biological activities, including anti-inflammatory, antibacterial, antitumor, antiviral, whitening, repairing skin damage caused by inflammation, immune regulation, and osteogenic activity. As a protein with great development potential, lactoferrin is widely used in the fields of food, medicine and cosmetics. The effect of lactoferrin on the skin is particularly prominent, and it has the potential to be used as a new raw material for skin care products. Researchers have reviewed biological activities of lactoferrin and its microbial mechanism of action. Therefore, this article focuses on the skin care efficacy of lactoferrin. This article reviews the latest research results of lactoferrin in skin care efficacy.

Key words: lactoferrin, skin care, efficacy, signaling pathway

Tong Xie, Wu Qiao, Tinghan Jia, and Ken Kaku. Progress in Skin Care Efficacy of Lactoferrin[J]. Medicine Research, 2022, 6(1-2): 210015-210015.

References

[1] Van Veen, H. A.; Geerts, M. E.; van Berkel, P. H.; Nuijens, J. H. The role of N-linked glycosylation in the protection of human and bovine lactoferrin against tryptic proteolysis. Eur. J. Biochem. 2004, 271, 678–684.
[2] Baggiolini, M.; De Duve, C.; Masson, P.; Heremans, J. Association of lactoferrin with specific granules in rabbit heterophil leukocytes. J. Exp. Med. 1970, 131, 559.
[3] Baker, E. N.; Baker, H. M. A structural framework for understanding the multifunctional character of lactoferrin. Biochimie 2009, 91, 3–10.
[4] Moore, S. A.; Anderson, B. F.; Groom, C. R.; Haridas, M.; Baker, E. N. Three-dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution. J. Mol. Biol. 1997, 274, 222–236.
[5] Masson, P.; Heremans, J.; Prignot, J.; Wauters, G. Immunohistochemical localization and bacteriostatic properties of an iron-binding protein from bronchial mucus. Thorax 1966, 21, 538.
[6] Mason, D.; Taylor, C. Distribution of transferrin, ferritin, and lactoferrin in human tissues. J. Clin. Pathol. 1978, 31, 316–327.
[7] Park, J. H.; Park, G. T.; Cho, I. H.; Sim, S. M.; Yang, J. M.; Lee, D. Y. An antimicrobial protein, lactoferrin exists in the sweat: proteomic analysis of sweat. Exp. Dermatol. 2011, 20, 369–371.
[8] Steijns, J. M.; Van Hooijdonk, A. Occurrence, structure, biochemical properties and technological characteristics of lactoferrin. Brit. J. Nutr. 2000, 84, 11–17.
[9] Yan, X.; He, H.; Meng, J.; Zhang, C.; Hong, M.; Tang, X. Preparation of lipid aspirin sustained-release pellets by solvent-free extrusion/spheronization and an investigation of their stability. Drug Dev. Ind. Pharm. 2012, 38, 1221–1229.
[10] Farnaud, S.; Evans, R. W. Lactoferrin—a multifunctional protein with antimicrobial properties. Mol. Immunol. 2003, 40, 395–405.
[11] Yang, N.; Strøm, M. B.; Mekonnen, S. M.; Svendsen, J. S.; Rekdal, Ø. The effects of shortening lactoferrin derived peptides against tumour cells, bacteria and normal human cells. J. Pept. Sci. 2004, 10, 37–46.
[12] Tsuda, H.; Kozu, T.; Iinuma, G.; Ohashi, Y.; Saito, Y.; Saito, D.; Akasu, T.; Alexander, D. B.; Futakuchi, M.; Fukamachi, K. Cancer prevention by bovine lactoferrin: from animal studies to human trial. Biometals 2010, 23, 399–409.
[13] Beljaars, L.; van der Strate, B. W.; Bakker, H. I.; Reker-Smit, C.; Wiegmans, F. C.; Harmsen, M. C.; Molema, G.; Meijer, D. K. Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo. Antivir. Res. 2004, 63, 197–208.
[14] Cornish, J.; Palmano, K.; Callon, K.; Watson, M.; Lin, J.; Valenti, P.; Naot, D.; Grey, A.; Reid, I. Lactoferrin and bone; structure–activity relationships. Biochem. Cell Biol. 2006, 84, 297–302.
[15] Duran, A.; Kahve, H. I. The use of lactoferrin in food industry. Acad. J. Sci. 2017, 7, 89–94.
[16] Elzoghby, A. O.; Abdelmoneem, M. A.; Hassanin, I. A.; Abd Elwakil, M. M.; Elnaggar, M. A.; Mokhtar, S.; Fang, J.-Y.; Elkhodairy, K. A. Lactoferrin, a multi-functional glycoprotein: active therapeutic, drug nanocarrier & targeting ligand. Biomaterials 2020, 120355.
[17] Wang, B.; Timilsena, Y. P.; Blanch, E.; Adhikari, B. Lactoferrin: Structure, function, denaturation and digestion. Crit. Rev. Food Sci. 2019, 59, 580–596.
[18] Wickett, R. R. Basics of skin structure. J. Cosmet. Sci. 2004, 55, 132–133.
[19] Sidhanee, A. Structure and function of the skin. Nursing 1983, 2, 239–242.
[20] Abdel‐Malek, Z.; Scott, M. C.; Suzuki, I.; Tada, A.; Im, S.; Lamoreux, L.; Ito, S.; Barsh, G.; Hearing, V. J. The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation. Pigm. Cell Res. 2000, 13, 156–162.
[21] Levy, C.; Khaled, M.; Fisher, D. E. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol. Med. 2006, 12, 406–414.
[22] Tamura, K.; Ohbayashi, N.; Ishibashi, K.; Fukuda, M. Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes. J. Biol. Chem. 2011, 286, 7507–7521.
[23] Ando, H.; Niki, Y.; Ito, M.; Akiyama, K.; Matsui, M. S.; Yarosh, D. B.; Ichihashi, M. Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J. Invest. Dermatol. 2012, 132, 1222–1229.
[24] Ebanks, J. P.; Koshoffer, A.; Wickett, R. R.; Schwemberger, S.; Babcock, G.; Hakozaki, T.; Boissy, R. E. Epidermal keratinocytes from light vs. dark skin exhibit differential degradation of melanosomes. J. Invest. Dermatol. 2011, 131, 1226–1233.
[25] Ishii, N.; Ryu, M.; Suzuki, Y. A. Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes. Biochem. Cell Biol. 2017, 95, 119–125.
[26] Kim, J.; Ko, Y.; Park, Y.-K.; Kim, N.-I.; Ha, W.-K.; Cho, Y. Dietary effect of lactoferrin-enriched fermented milk on skin surface lipid and clinical improvement of acne vulgaris. Nutrition 2010, 26, 902–909.
[27] Rezk, M.; Dawood, R.; Abo-Elnasr, M.; Al Halaby, A.; Marawan, H. Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial. J. Matern-Fetal Neo M. 2016, 29, 1387–1390.
[28] Legrand, D.; Elass, E.; Carpentier, M.; Mazurier, J. Lactoferrin: a modulator of immune and infl ammatory responses. Cell Mol Life Sci. 2005, 62, 2549–2559.
[29] Orsi, N. The antimicrobial activity of lactoferrin: current status and perspectives. Biometals 2004, 17, 189–196.
[30] Yamauchi, K.; Tomita, M.; Giehl, T.; Ellison 3rd, R. Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect. Immun. 1993, 61, 719–728.
[31] Spadaro, M.; Caorsi, C.; Ceruti, P.; Varadhachary, A.; Forni, G.; Pericle, F.; Giovarelli, M. Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells. FASEB J. 2008, 22, 2747–2757.
[32] Actor, J. K.; Hwang, S.-A.; Kruzel, M. L. Lactoferrin as a natural immune modulator. Curr. Pharm. Design 2009, 15, 1956–1973.
[33] Wang, G.; Li, X.; Wang, Z. APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res. 2009, 37, D933–D937.
[34] Ganz, T. Antimicrobial polypeptides. J. Leukocyte Biol. 2004, 75, 34–38.
[35] Bowdish, D.; Davidson, D.; Hancock, R. Immunomodulatory properties of defensins and cathelicidins. Curr. Top. Microbiol. Immunol. 2006, 27-66.
[36] Wiesner, J.; Vilcinskas, A. Antimicrobial peptides: the ancient arm of the human immune system. Virulence 2010, 1, 440–464.
[37] Levy, O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J. Leukocyte Biol. 2004, 76, 909–925.
[38] Diamond, G.; Beckloff, N.; Ryan, L. Host defense peptides in the oral cavity and the lung: similarities and differences. J. Dent. Res. 2008, 87, 915–927.
[39] Nevalainen, T. J.; Graham, G. G.; Scott, K. F. Antibacterial actions of secreted phospholipases A2. Review. Bba-Mol. Cell Biol. L 2008, 1781, 1–9.
[40] Gutsmann, T.; Seydel, U. Impact of the glycostructure of amphiphilic membrane components on the function of the outer membrane of Gram-negative bacteria as a matrix for incorporated channels and a target for antimicrobial peptides or proteins. Eur. J. Cell Biol. 2010, 89, 11–23.
[41] Ammons, M. C. B.; Ward, L. S.; James, G. A. Anti‐biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings. Int. Wound J. 2011, 8, 268–273.
[42] Conneely, O. M. Antiinflammatory activities of lactoferrin. J. Am. Coll. Nutr. 2001, 20, 389S–395S.
[43] Farid, A. S.; El Shemy, M. A.; Nafie, E.; Hegazy, A. M.; Abdelhiee, E. Y. Anti-inflammatory, anti-oxidant and hepatoprotective effects of lactoferrin in rats. Drug Chem. Toxicol. 2021, 44, 286–293.
[44] Takayama, Y.; Aoki, R. Roles of lactoferrin on skin wound healing. Biochem. Cell Biol. 2011, 90, 497–503.
[45] Engelmayer, J.; Blezinger, P.; Varadhachary, A. Talactoferrin stimulates wound healing with modulation of inflammation. J Surg. Res. 2008, 149, 278–286.
[46] Uchida, R.; Aoki, R.; Aoki-Yoshida, A.; Tajima, A.; Takayama, Y. Promoting effect of lactoferrin on barrier function and epithelial differentiation of human keratinocytes. Biochem. Cell Biol. 2017, 95, 64–68.
[47] Eckert, R. L.; Crish, J. F.; Efimova, T.; Dashti, S. R.; Deucher, A.; Bone, F.; Adhikary, G.; Huang, G.; Gopalakrishnan, R.; Balasubramanian, S. Regulation of involucrin gene expression. J. Invest. Dermatol. 2004, 123, 13–22.
[48] Goldstein, J. L.; DeBose-Boyd, R. A.; Brown, M. S. Protein sensors for membrane sterols. Cell 2006, 124, 35–46.
[49] Yokoyama, A.; Makishima, M.; Choi, M.; Cho, Y.; Nishida, S.; Hashimoto, Y.; Terui, T. Induction of SREBP-1c mRNA by differentiation and LXR ligand in human keratinocytes. J. Invest. Dermatol. 2009, 129, 1395–1401.
[50] Blais, A.; Fan, C.; Voisin, T.; Aattouri, N.; Dubarry, M.; Blachier, F.; Tomé, D. Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study. Biometals 2014, 27, 857–874.
[51] Lyons, T. E.; Miller, M. S.; Serena, T.; Sheehan, P.; Lavery, L.; Kirsner, R. S.; Armstrong, D. G.; Reese, A.; Yankee, E. W.; Veves, A. Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study. Am. J. Surg. 2007, 193, 49–54.
[52] Tang, L.; Wu, J.; Ma, Q.; Cui, T.; Andreopoulos, F.; Gil, J.; Valdes, J.; Davis, S.; Li, J. Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization. Brit. J. Dermatol. 2010, 163, 38–47.
[53] Hagiwara, T.; Shinoda, I.; Fukuwatari, Y.; Shimamura, S. Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line, IEC-18, in the presence of epidermal growth factor. Biosci. Biotech. Bioch. 1995, 59, 1875–1881.
[54] Tang, L.; Cui, T.; Wu, J. J.; Liu‐Mares, W.; Huang, N.; Li, J. A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival. Wound Repair Regen. 2010, 18, 123–131.
[55] Takayama, Y.; Mizumachi, K. Effects of lactoferrin on collagen gel contractile activity and myosin light chain phosphorylation in human fibroblasts. FEBS Lett. 2001, 508, 111–116.
[56] Takayama, Y.; Mizumachi, K.; Takezawa, T. The bovine lactoferrin region responsible for promoting the collagen gel contractile activity of human fibroblasts. Biochem. Bioph. Res. Co. 2002, 299, 813–817.
[57] Ashby, B.; Garrett, Q.; Willcox, M. Bovine lactoferrin structures promoting corneal epithelial wound healing in vitro. Invest Ophth. Vis. Sci. 2011, 52, 2719–2726.
[58] Takayama, Y.; Takahashi, H.; Mizumachi, K.; Takezawa, T. Low density lipoprotein receptor-related protein (LRP) is required for lactoferrin-enhanced collagen gel contractile activity of human fibroblasts. J. Biol. Chem. 2003, 278, 22112–22118.
[59] Saito, S.; Takayama, Y.; Mizumachi, K.; Suzuki, C. Lactoferrin promotes hyaluronan synthesis in human dermal fibroblasts. Biotechnol. Lett. 2011, 33, 33–39.
[60] Alexander, D. B.; Iigo, M.; Yamauchi, K.; Suzui, M.; Tsuda, H. Lactoferrin: an alternative view of its role in human biological fluids. Biochem. Cell Biol. 2012, 90, 279–306.
[61] Legrand, D.; Elass, E.; Carpentier, M.; Mazurier, J. Interactions of lactoferrin with cells involved in immune function. Biochem. Cell Biol. 2006, 84, 282–290.
[62] Suzuki, Y.; Lopez, V.; Lönnerdal, B. Mammalian lactoferrin receptors: structure and function. Cell Mol. Life Sci. 2005, 62, 2560–2575.
[63] May, P.; Herz, J.; Bock, H. Molecular mechanisms of lipoprotein receptor signalling. Cell Mol. Life Sci. 2005, 62, 2325–2338.
[64] Willnow, T. E.; Goldstein, J. L.; Orth, K.; Brown, M. S.; Herz, J. Low density lipoprotein receptor-related protein and gp330 bind similar ligands, including plasminogen activator-inhibitor complexes and lactoferrin, an inhibitor of chylomicron remnant clearance. J. Biol. Chem. 1992, 267, 26172–26180.
[65] Grey, A.; Banovic, T.; Zhu, Q.; Watson, M.; Callon, K.; Palmano, K.; Ross, J.; Naot, D.; Reid, I. R.; Cornish, J. The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Mol. Endocrinol. 2004, 18, 2268–2278.
[66] Ikoma-Seki, K.; Nakamura, K.; Morishita, S.; Ono, T.; Sugiyama, K.; Nishino, H.; Hirano, H.; Murakoshi, M. Role of LRP1 and ERK and cAMP signaling pathways in lactoferrin-induced lipolysis in mature rat adipocytes. PLoS One 2015, 10, e0141378.
[67] Suzuki, Y. A.; Shin, K.; Lönnerdal, B. Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry 2001, 40, 15771–15779.
[68] Jiang, R.; Lönnerdal, B. Apo-and holo-lactoferrin stimulate proliferation of mouse crypt cells but through different cellular signaling pathways. Int. J. Biochem. Cell B 2012, 44, 91–100.
[69] Grey, A.; Zhu, Q.; Watson, M.; Callon, K.; Cornish, J. Lactoferrin potently inhibits osteoblast apoptosis, via an LRP1-independent pathway. Mol. Cell Endocrinol. 2006, 251, 96–102.
[70] Ando, K.; Hasegawa, K.; Shindo, K. i.; Furusawa, T.; Fujino, T.; Kikugawa, K.; Nakano, H.; Takeuchi, O.; Akira, S.; Akiyama, T. Human lactoferrin activates NF-κB through the Toll‐like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling. FASEB J. 2010, 277, 2051–2066.
[71] Takayama, Y.; Aoki, R.; Uchida, R.; Tajima, A.; Aoki-Yoshida, A. Role of CXC chemokine receptor type 4 as a lactoferrin receptor. Biochem. Cell Biol. 2017, 95, 57–63.