Biological Function of Lactoferrin
Colostrum and Lactoferrin can respond to various physiological and environmental changes, therefore it is considered a key component of the innate defense system. Lactoferrin exhibits strong antibacterial activity against various bacteria, fungi, yeast, viruses, and parasites. It also has anti-inflammatory and anticancer activities, as well as multiple enzyme functions. Lactoferrin plays a crucial role in maintaining cellular iron levels in the body.
1. Antibacterial Activity
The biological function of lactoferrin, which was first discovered and widely studied, is its antibacterial ability. Lactoferrin has a broad-spectrum ability to resist Gram positive bacteria, Gram negative bacteria, and fungi, and can effectively inhibit the growth of Escherichia coli, Salmonella typhi, Streptococcus, Legionella pneumophila, and Staphylococcus aureus. In clinical practice, oral treatment with lactoferrin in patients reduces gastrointestinal bacterial infections, but does not affect the growth of lactobacilli and bifidobacteria.
It is generally believed that lactoferrin competitively deprives bacteria of the iron required for growth by chelating iron ions, thereby inhibiting bacterial growth. There are also studies indicating that lactoferrin can bind with lipid A, promoting the detachment of lipid A from the bacterial wall of Gram negative bacteria, leading to bacterial death. The N-terminus of lactoferrin contains a sequence encoding lactoferrin, which is a naturally active antimicrobial peptide.
2. Antiviral Activity
Colostrum and Lactoferrin can help the body resist various viral infections. Intestinal infections caused by rotavirus, enterovirus, and adenovirus can all be treated with lactoferrin. In the early stages of infection, lactoferrin can inhibit adenovirus replication, prevent virus adsorption on target cells, and prevent infection. When studying the norovirus that causes infectious diarrhea, it was found that lactoferrin can reduce the damage of cytotoxics, reduce the number of viral cells, prevent virus cell adhesion, inhibit virus replication, and increase the expression of antiviral cytokines, thereby killing the norovirus. Lactoferrin can inhibit the activity of HIV-1 reverse transcriptase and splicing enzyme, preventing HIV virus infection of cells. In addition, lactoferrin can also resist the invasion of viruses such as HSV-1, HCMV, and HCV into the body.
3. Antifungal Activity
Human lactoferrin, bovine lactoferrin, and lactoferrin derived peptides all have in vitro activity against human pathogenic fungi, especially Candida albicans and several other types of Candida. Lactoferrin can kill Candida albicans and Clostridium cruzi by altering the permeability of cell surfaces, just like antibacterial agents. Lactoferrin can alter the cytoplasmic and mitochondrial membrane permeability of Cryptococcus neoformans and Candida albicans. The antifungal mechanism of lactoferrin is achieved through interaction with the cell surface rather than iron deprivation.
4. Anticancer
In recent years, the anticancer effect of lactoferrin has been widely reported. Oral administration of bovine lactoferrin to rodents can inhibit the formation of tumors induced by chemical methods. Clinical trials have confirmed that lactoferrin can inhibit the occurrence and development of tumors. Colostrum Lactoferrin has the ability to regulate cytokine production in cancer. Lactoferrin induces cell apoptosis and inhibits tumor growth in vitro. It can also prevent the transition from G1 to S in the cell cycle of malignant cells.
In addition, treating mouse tumors with recombinant human lactoferrin can inhibit tumor growth, increase levels of anti-cancer cytokines (such as IL-18), and activate NK cells and CD8+T lymphocytes. Recently, clinical trials have shown that bovine lactoferrin can inhibit colorectal cancer, while human lactoferrin can reduce the risk of colon cancer.
For breast cancer, lactoferrin capsule can inhibit the growth of its tumor cells. Adding exogenous lactoferrin to the medium of breast cancer cell line (MDA-MB-231) will lead to cell cycle stagnation in G1/S transition period. In addition, lactoferrin induces growth arrest of Smad-2 in HeLa cells.
5. Immune Regulation and Anti-inflammatory Activity
Due to the widespread distribution of immune care lactoferrin in the exocrine fluid of the body, it can serve as the first natural immune barrier to participate in immune regulation. Lactoferrin is one of the important inflammatory response regulatory factors and an important component involved in regulating the immune system. It can protect the body from microbial infections, reduce the incidence of E. coli and infectious diarrhea, and improve the growth status of weaned piglets.
For newborns with underdeveloped immune systems, colostrum rich in lactoferrin can help activate and regulate the function of the immune system, while promoting the rapid establishment of the self immune system. Oral administration of bovine lactoferrin increases the number of cells in lymph nodes and spleen, enhances the activity of peritoneal macrophages and spleen NK cells, and enhances Th1 type T cells IL-12 and IFY- γ Wait for the production of cytokines.
Immune lactoferrin inhibits programmed cell death of immune cells by blocking the signaling pathway of cell apoptosis; It is also possible to regulate the maturation and differentiation of T lymphocytes, as well as the balance of Th1/Th2 cytokines, through interaction with antigen-presenting cells.
6. Enzymatic Activity
Lactoferrin can act as an enzyme in certain catalytic reactions. There are significant similarities in certain motifs between lactoferrin and ribonuclease A. Lactoferrin has DNA binding characteristics and can play a role in transcriptional activation of specific DNA sequences or serve as a signaling mediator.
Among all milk proteins, lactoferrin has the highest amylase and ATPase activity, however, they are not the only enzymatic activity. The various activities exhibited by lactoferrin are attributed to changes in its protein properties. Lactoferrin has multiple isotypes, different degrees of glycosylation, different tertiary structures, and degree of oligomerization.
Application
The extensive biological functions of lactoferrin determine its application in fields such as food, cosmetics, animal production, and medicine. It can be used as an antioxidant, immune promoter, iron supplement, drug carrier, etc; Among them, it is particularly widely used in infant formula milk powder.
1. Food Industry
As of 2021, the market is rich and diverse in products containing lactoferrin, including yogurt, skim milk, health foods, and fermented dairy products. In the late 20th century, Japanese dairy companies began producing and selling infant formula containing lactoferrin. Adding good health lactoferrin to infant formula has many benefits, including promoting iron absorption and improving gut microbiota.
These products containing lactoferrin have been proven to be very beneficial for health in clinical and animal trials. The addition of lactoferrin to fermented dairy products, infant and toddler food, soy protein products, and meat products is popular in countries and regions such as Japan and South Korea to supplement lactoferrin, enhance the body's immunity, and prevent diseases such as viral colds and intestinal infections.
2. Cosmetic
Lactoferrin is a natural substance in the human body that has a wide range of antibacterial, anti-inflammatory, melanin inhibiting, and collagen promoting effects. Therefore, it can be used as an effective ingredient in the development and utilization of cosmetic preparations. In the development of whitening cosmetics, the raw materials have a certain degree of stability during the processing, while lactoferrin has extremely high stability and can be used as raw materials for processing into whitening agents.
Research has shown that using lactoferrin to identify the whitening function in animal skin models can reduce the formation of melanin, and the ability to inhibit melanin is directly proportional to the content of lactoferrin. This indicates that lactoferrin can be absorbed by the skin, thus playing a whitening role. Lactoferrin can promote collagen synthesis in osteoblasts in the human body, compensate for the loss of collagen caused by age and environmental factors, and have a whitening effect on the human skin.
3. Animal Production
Adding lactoferrin to the feed of sows can obtain a large amount of endogenous lactoferrin, which can reduce the probability of iron deficiency anemia in piglets, improve their immunity, and promote their growth. Adding lactoferrin to the diet of piglets can improve their gut microbiota, prevent intestinal diarrhea, and enhance their ability to absorb nutrients.
Adding lactoferrin to feed can prevent it from being oxidized and decomposed, while enhancing the nutritional content of the feed. Bulk lactoferrin also has the function of maintaining its physiological function well during high-temperature feed processing, so it can be used as a green feed additive for animal feeding.
4. Disease
Lactoferrin not only regulates iron metabolism in the body, but also plays an important role in anti-inflammatory and antioxidant activities. Lactoferrin receptors exist on the surface of cell membranes, with a molecular weight of around 105 kDa. Common target cells include mucosal epithelial cells, liver cells, monocytes, macrophages, lymphocytes, and bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa.
Lactoferrin binds to bacterial cell surface receptors and can activate intracellular signaling pathways or enter the nucleus through endocytosis, participating in immune and antibacterial functions in the body. Research has confirmed that lactoferrin receptors are highly expressed in neurons and endothelial cells of capillaries in Parkinson's disease patients, and their binding inhibits the spread of prion proteins; The role of lactoferrin suggests its potential application value in the prevention and treatment of neurodegenerative diseases.
