Characteristics and therapeutic properties of lactoferrin protein

Abstract

Lactoferrin, a multi-functional glycoprotein, is found in body fluids and exocrine glands. It serves as an essential iron-binding protein and has various beneficial properties. It plays a key role in iron regulation, immune modulation, lipid metabolism, gut health, and bone health. It shows potent antimicrobial, anti-inflammatory, and anti-carcinogenic properties. Its therapeutic potential extends to various conditions, including aging-related and chronic diseases, gastrointestinal health, neurodegenerative diseases, and cancer. It also shows promise for treating anemia and promoting healthy aging. Understanding its complex interactions with pathogens highlights its role as a modulator of immune responses. This review article emphasizes its multifaceted functions and its potential as a valuable therapeutic agent for human health.

Keywords: Lactoferrin, glycoprotein, health, anti-inflammatory, anti-aging.

 

Introduction

Lactoferrin, also known as lactotransferrin, is a major iron-binding protein in milk. It was first discovered in bovine milk in 1939 and later isolated from human milk in 1960 by Johannson [1]. It comprises 703 amino acids with a molecular weight of approximately 80 kDa [2]. It is found in various body fluids such as serum, tears, semen, and milk. In human milk, lactoferrin plays a significant role as a major whey protein, making up around 10-30% of the total whey protein content. Human colostrum, the initial milk produced after childbirth, is particularly abundant in lactoferrin, with an average concentration of about 5 to 6 mg/ml. However, as breastfeeding time increases, the concentration of lactoferrin in milk decreases to around 1 mg/ml [3]. In addition, lactoferrin is also produced by the hematopoietic tissue of the bone marrow and is present in neutrophil granules. In humans and animals, Lactoferrin is mainly found in the products of exocrine glands located at the gateways of the digestive, respiratory, and reproductive systems [4, 5]. Lactoferrin is a multi-functional iron-binding glycoprotein that can modulate immunity and inflammation and enhance iron absorption. Lactoferrin has been reported as an effective therapy in the treatment of anemia in both pediatrics and adults [5]. Lactoferrin is a multifunctional protein that deserves to be called a “miracle molecule”, exhibiting several other beneficial properties such as anti-pathogenic, anti-cancer, anti-inflammatory, immunomodulatory, and DNA modulatory activities [6].

Given the growing interest in lactoferrin and its numerous beneficial properties, it is pertinent to explore its potential applications in addressing current health challenges. With increasing demand for proteins that offer health benefits, lactoferrin's therapeutic potential becomes even more relevant. Therefore, a review article on lactoferrin's diverse functions, its role in different human diseases, and its potential impact on the health scenario can provide valuable insights for researchers and healthcare professionals. The article could also highlight the current protein demand and how lactoferrin could serve as a promising candidate to address health-related concerns. A perspective on the background of the study will further contextualize the importance of exploring lactoferrin's applications, making it a valuable addition to the existing literature on biotechnological advancements.

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Characteristics and Properties

Lactoferrin is a whey protein found in the milk of most mammals except for dogs and rats. Its concentration varies depending on the lactation phase, with colostrum having up to seven times more lactoferrin than mature milk. Interestingly, lactoferrin is not just limited to milk; the human body's cells can also produce it. This essential protein is present in various organs and cells, including the kidneys, lungs, gallbladder, pancreas, intestine, liver, and more. It is also found in body fluids like saliva, tears, sperm, and urine, as well as in immune system cells. Lactoferrin appears wherever the body needs quick and effective protection against external threats [7, 8].

Lactoferrin is a multifaceted glycoprotein with numerous vital functions in the human body. Its distinctive structure, which consists of two globular lobes connected by an alpha-helix, enables various post-translational modifications, which affect its biological activity. As a member of the transferrin family, lactoferrin's remarkable iron-binding ability helps maintain iron homeostasis, safeguarding against iron overload and supporting the immune response by limiting pathogen access to iron. In addition to regulating iron, lactoferrin helps with lipid metabolism, improves gut health by encouraging the growth of good bacteria, and helps keep bones healthy by promoting osteogenesis and stopping processes that break down bones. Furthermore, its antioxidant properties counteract oxidative stress, protecting cells from damage [6].

 

Therapeutic properties

Several therapeutic properties of lactoferrin protein are reported in the literature as shown in Figure 1.

Figure 1. Therapeutic properties of lactoferrin protein

Anti-aging

Aging is a natural process influenced by time, genetics, and environmental factors, leading to increased susceptibility to diseases. Lactoferrin has pleiotropic anti-aging effects, acting as an antioxidant, anti-inflammatory, and anticancer agent. Lactoferrin regulates gene expression, cell growth, and inflammation while protecting cells and organs, extending lifespan [9]. It plays a role in neuroprotection, helps with tissue repair and homeostasis, and shows promise in age-related disease treatment and diagnosis. Lactoferrin aids in Alzheimer's and Parkinson's disease, obesity control, and glucose metabolism in diabetes patients and it also benefits cardiovascular health. By promoting overall well-being, lactoferrin holds the potential to be a valuable component in the pursuit of healthy aging [6].

Implications in Chronic Diseases

Chronic diseases like cardiovascular disease, diabetes, and osteoporosis are major global health concerns. Lactoferrin has shown promising effects in combating these diseases. In diabetes, camel milk-derived lactoferrin interacts with the insulin receptor, aiding in blood sugar regulation. Lactoferrin also contains peptides with antihypertensive properties, helping maintain healthy blood pressure levels for cardiovascular health [10]. Moreover, it plays a role in bone growth and healing, promoting the proliferation of bone-building cells while inhibiting bone breakdown. Additionally, lactoferrin aids in wound healing, especially in diabetic conditions, by promoting bacterial eradication and supporting tissue repair. Overall, Lactoferrin shows great potential in managing chronic diseases and improving overall health [4, 2, 17].

Gastrointestinal health

Lactoferrin plays a significant role in maintaining intestinal health by inhibiting harmful bacteria while promoting beneficial ones like Lactobacillus acidophilus and Bifidobacterium bifidum. This helps balance intestinal flora. It is also used as a biomarker for inflammatory bowel disease. Patients with conditions like ulcerative colitis or Crohn's disease have higher levels of lactoferrin in their stool and serum. In clinical trials, lactoferrin has shown promise in suppressing colorectal polyps by enhancing immune responsiveness [4]. Additionally, lactoferrin supports the development of healthy gut microbiota in newborns, reducing the risk of late-onset sepsis in preterm infants. However, some studies suggest that lactoferrin might not reduce the risk of LOS in very preterm infants. Lactoferrin also aids in maintaining and repairing intestinal mucosal tissues, preventing intestinal infections like rotavirus [11]. In general, lactoferrin demonstrates various beneficial effects on intestinal health and immune function.

Neurodegenerative

Patients with neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis often experience imbalanced iron levels and oxidative stress. The blood-brain barrier makes it challenging for many drugs to enter the brain, but lactoferrin can cross it rapidly via receptor-mediated transcytosis and accumulate in brain capillary cells. Lactoferrin receptors are present in glioma cells, brain microvessels, and neurons. By binding to specific lipoprotein receptors, it helps regulate neuronal differentiation, promoting the expression of neuron-specific enolase (NSE) and encouraging neuronal cell differentiation. Studies have shown higher lactoferrin levels in the saliva and tears of Parkinson's patients, but lower levels in Alzheimer's patients compared to non-disease controls. Researchers have used lactoferrin to target drug delivery to the brain, resulting in improved memory and increased acetylcholine levels in mice. These findings highlight the potential of lactoferrin as a promising candidate for neurodegenerative disease treatment [4, 12, 13].

Cancer

Lactoferrin has shown significant potential in damaging various cancer cells. It can lead to cell cycle arrest, damage the cytoskeleton, induce apoptosis (cell death), and reduce cell migration. For example, in oral squamous cell carcinoma (OSCC) cells, lactoferrin selectively inhibits cell proliferation and induces apoptosis through specific pathways. The combination of lactoferrin and linolenic acid can activate apoptotic pathways to inhibit colorectal tumor growth and suppress xenograft esophageal tumors in mice by inhibiting specific signaling pathways. These findings suggest that lactoferrin holds promise as a potential therapeutic agent against cancer cells [4].

Anti-microbial

Lactoferrin is well-known for its diverse antimicrobial properties, including its ability to inhibit bacteria, viruses, and fungi, as well as its anti-inflammatory and anti-carcinogenic effects. One crucial aspect of lactoferrin's antimicrobial function is its ability to limit iron availability to microbes, which is essential for their growth. However, bacteria have developed strategies to sequester iron from lactoferrin and other host proteins. Some pathogens, like Neisseria, have evolved systems to directly hijack iron from lactoferrin and transferrin, using specific surface receptors. Despite being exploited by bacteria, lactoferrin remains a significant element of the host defense system and plays a crucial role in modulating immune responses. In human milk, apolactoferrin competes with siderophilic bacteria for iron, disrupting their proliferation and providing protection against microbial pathogens. Understanding the complex interplay between lactoferrin and bacteria helps highlight its potential as a modulator of innate and adaptive immune responses [4, 13].

Anti-viral

Lactoferrin exhibits potent antiviral activity against a wide range of both naked and enveloped DNA and RNA viruses. It works by inhibiting viral entry into host cells. Lactoferrin can attach directly to viral particles or block their cellular receptors. This includes HSPGs (heparan sulfate proteoglycans), which are molecules on the cell membrane that viruses use to get inside the cell. Lactoferrin prevents viruses like Herpes simplex virus, human papillomavirus, human immunodeficiency virus (HIV), and retrovirus from entering host cells by binding to HSPGs, acting as a protective barrier against viral infection [13, 15, 16].

 

Conclusion

Lactoferrin is a versatile and multifunctional protein with diverse beneficial properties in the human body. Its iron-binding ability helps maintain iron homeostasis and supports the immune response by limiting pathogen access to iron. Beyond iron regulation, it plays essential roles in lipid metabolism, gut health, bone health, and protection against oxidative stress. It exhibits potent antimicrobial activity against bacteria, viruses, and fungi and demonstrates anti-inflammatory and anti-carcinogenic effects. Lactoferrin's therapeutic potential extends to various human diseases, including aging-related conditions, chronic diseases, gastrointestinal health, neurodegenerative diseases, and cancer. Understanding the interplay between lactoferrin and bacteria, as well as its antiviral capabilities, highlights its significance as a modulator of immune responses and a potential therapeutic candidate in disease management.

 

References

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 By: Sareeta Baig