Discovered by MONTREUIJ and JOHANSONB in 1960, lactoferrin (LF) is a multifunctional non-heme iron-binding glycoprotein first identified in breast milk, with its existence in various bodily fluids and cells later confirmed. It is abundant in mammalian milk, particularly in human milk (1.0-3.2mg/ml, 10 times that of cow's milk), with higher levels in colostrum (6-14mg/ml) and accounting for 20% of total protein in regular breast milk. Lactoferrin exhibits diverse biological activities, including broad-spectrum antibacterial, antiviral, and antiparasitic effects, regulation of iron balance, promotion of bone marrow cell production, enhancement of immune function, inhibition of tumor cell growth, anti-inflammation, catalysis, anti-allergy, and radiation protection. It can synergize with antibiotics and antifungal agents, and is recognized as a promising antibacterial/anticancer drug and additive for foods (e.g., sports and functional foods approved by the FDA) and cosmetics, being a key component of the innate immune system.
Lactoferrin (LF) is an important non-heme iron-binding glycoprotein in milk and a monomeric glycoprotein with bactericidal activity in neutrophil granules, discovered by scientists MONTREUIJ and JOHANSONB in 1960. Lactoferrin is a multifunctional protein that has broad-spectrum antibacterial, antiviral infection, regulation of iron balance in the body, promotion of bone marrow cell production, and regulation of the body's immune function.
Source
In 1939, Sorensen and others obtained a red protein when isolating whey protein. Polis and others also obtained partially purified red protein when isolating Lp. However, it was not until 1959 that Groves obtained a pure red substance using chromatography and confirmed that this red substance is an iron-binding glycoprotein, called lactoferrin.
Lactoferrin was discovered in breast milk in 1960 by scientists MONTREUIJ and JOHANSONB. Subsequently, scientists such as BAGGIN discovered this protein in the body fluids and various cells of some organisms and began extensive research. Studies have shown that lactoferrin (LF) is a natural protein in animal colostrum and a multifunctional protein. It has broad-spectrum antibacterial and antiviral infection effects, can regulate iron balance in the body, regulate the production of bone marrow cells, promote cell growth, regulate the body's immune function, enhance the body's disease resistance, inhibit the growth of human tumor cells, and can synergize with a variety of antibiotics and antifungal agents to more effectively treat diseases.
Distribution
Lactoferrin is widely distributed in mammalian milk and various other tissues and their secretions (including tears, semen, bile, synovial fluid and other internal and external secretions, and neutrophils). The concentration of lactoferrin in human milk is about 1.0-3.2 mg/ml, which is 10 times that in cow's milk (the content in cow's milk is 0.02-0.35 mg/ml) and accounts for 20% of the total protein in ordinary breast milk. During lactation, the lactoferrin content changes with the lactation time. For example, lactoferrin in human colostrum can reach 6-14 mg/ml, and drops to 1 mg/ml during the regular lactation period.
Lactoferrin is valued because it can take away the iron needed for bacterial growth to inhibit bacterial growth, or destroy bacterial cell membranes to kill bacteria. It can also enhance immunity and inhibit infections caused by viruses, such as rotavirus and enterovirus 71 in enteroviruses.
Efficacy
Lactoferrin and its protein degradation product - lactoferrin peptide have a wide range of biological activities, including broad-spectrum antibacterial effects, anti-inflammation, inhibition of tumor cell growth, and regulation of the body's immune response. They are considered a new type of antibacterial and anti-cancer drug and a food and cosmetic additive with great development potential. For example, the U.S. Food and Drug Administration has long allowed lactoferrin to be used as a food additive in sports and functional foods.
Lactoferrin is a component of the innate immune system. In addition to its main function of binding and transporting iron ions, lactoferrin also has the functions and properties of antibacterial, antiviral, antiparasitic, catalysis, anti-cancer, anti-allergy and radiation protection.
Related Studies
Lactoferrin's Regulatory Effects on Lipid Metabolism and Hepatic Steatosis in High-Fat Diet-Induced Obese Mice
According to a 2018 study entitled Lactoferrin attenuates high-fat diet-induced hepatic steatosis and lipid metabolic dysfunctions by suppressing hepatic lipogenesis and down-regulating inflammation in C57BL/6J mice, lactoferrin alleviates high-fat diet-induced hepatic steatosis and lipid metabolic disorders in C57BL/6J mice by inhibiting hepatic lipogenesis and down-regulating inflammatory responses.
Studies have shown that lactoferrin has a regulatory effect on lipid metabolism, but its regulatory mechanism remains unclear. This study explored the beneficial effects of lactoferrin in high-fat diet-induced obese C57BL/6J mice and its potential mechanism. Oral administration of lactoferrin (100 mg/g body weight) for 15 weeks significantly reduced body weight gain, visceral fat content, and serum levels of glucose, leptin, and lipids in high-fat diet-induced obese mice. Hepatic steatosis in obese mice was significantly improved. The expression of adipogenic and inflammation-related genes and proteins (SREBP-1c, FAS, MCP-1, leptin) in the liver and epididymal adipose tissue of obese mice was inhibited.
Studies have shown that lactoferrin positively regulates lipid metabolism in obese mice and improves hepatic lipid deposition. The mechanism of these effects may be attributed to the inhibition of adipogenesis in the liver and epididymal adipose tissue and the improvement of inflammation. This is a rarely reported finding in high-fat diet-induced obese mouse models without any energy restriction that lactoferrin alleviates hepatic steatosis by inhibiting adipogenesis.
Lactoferrin Alleviates Western Diet-Induced Cognitive Impairment via the Microbiota-Gut-Brain Axis
Lactoferrin (Lf) has been shown to improve cognitive function in several animal models. To clarify the underlying mechanism, male C57BL/6J mice were randomly divided into four groups: control group (CON), Western diet group (WD), lactoferrin group (Lf), and lactoferrin + antibiotic group (AB). The Lf group was given Lf via gavage, while the Lf + AB group received additional antibiotic solution via gavage. After 16 weeks of intervention, Lf improved cognitive function as indicated by behavioral tests. It also increased the length and curvature of postsynaptic densities and upregulated the expression of related proteins, suggesting improvements in hippocampal neurons and synapses. Immunofluorescence analysis showed that Lf inhibited the activation and proliferation of microglia.
Moreover, Lf reduced the levels of proinflammatory cytokines in serum and downregulated their protein expression in the hippocampal region. It also inhibited the activation of the NF-κB/NLRP3 inflammasome in the hippocampus. Meanwhile, Lf upregulated the expression of tight junction proteins and increased the abundance of Bacteroidetes at the phylum level and Roseburia at the genus level, which is beneficial to the intestinal barrier and cognitive function. Antibiotics eliminated the effect of long-term Lf intervention on cognitive impairment in the Lf + AB group, suggesting that the intestinal microbiota is involved in the action of Lf. Short-term Lf intervention (2 weeks) prevented WD-induced changes in the intestinal microbiota without causing behavioral alterations, supporting the timing of intestinal microbiota reaching the brain. Therefore, Lf intervention alleviates cognitive impairment by inhibiting microglial activation and neuroinflammation via the microbiota-gut-brain axis.
The study results demonstrate the beneficial effects of Lf intervention on WD-induced cognitive dysfunction in obese mice by reducing synaptic damage and inhibiting microglial activation. The underlying mechanism may involve reducing neuroinflammation by inhibiting the activation of the NF-κB/NLRP3 inflammasome and improving changes in intestinal microbial composition via the microbiota-gut-brain axis. More well-designed experiments are needed to clarify the complex interactions between the intestinal microbiota, inflammation, and cognitive function.