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Lactoferrin's Cross-Industry Applications

Time:2023-09-13 Hits:358

Lactoferrin (LF) is a naturally occurring, harmless iron-binding glycoprotein with diverse biological activities. It is produced by mammary gland epithelial cells and neutrophils in mammals and is widely distributed in tissues with secretory functions and their secretions.


Lactoferrin has a relative molecular weight of about 76,000 to 81,000 Daltons, making it one of the most potent iron-binding proteins in its family. It consists of approximately 700 amino acid residues. Lactoferrin exists in three forms: apo-LF, holo-LF, and hemi-LF. It exhibits good stability at a denaturation temperature of 73.1°C and is particularly stable under acidic conditions.


Introduction to Lactoferrin:

Lactoferrin is a major component of whey protein in breast milk, constituting 10-15% of total milk protein.
Lactoferrin is a naturally occurring glycoprotein with immunomodulatory functions.
The concentration of lactoferrin in breast milk is 20 times higher than in cow's milk, with levels of 6-8g/L in colostrum and 2-4g/L in mature milk.
Cow colostrum contains about 1g/L of lactoferrin, while mature cow's milk contains 0.1-0.2g/L.
The content of lactoferrin in formula milk powder is ≤1.0g/kg (China Food Nutritional Fortifier Standard).


Antibacterial and Antiviral Applications:

Lactoferrin possesses broad-spectrum antibacterial and antiviral properties with diverse and multilayered mechanisms of action. In terms of antibacterial effects, lactoferrin inhibits bacterial growth by sequestering iron and directly kills bacteria through its cationic antimicrobial domain. It also activates immune cells to release antimicrobial substances. Concerning antiviral effects, lactoferrin binds to host cells and viral particles, inhibiting a variety of viruses including SARS-CoV-2. This is likely achieved by modulating factors such as inflammation, iron balance, and oxidative stress that affect various aspects of viral infection. Thus, lactoferrin plays a potentially significant role in immune defense and disease treatment, offering new possibilities in tackling
antibacterial and antiviral challenges.


"Functional properties of Lactoferrin and the application of Lactoferrin in domestic and overseas regions" states that lactoferrin demonstrates broad-spectrum antibacterial activity both in vitro and in vivo, effectively preventing microbial infections. For bacteria, lactoferrin operates through three distinct mechanisms: firstly, it exhibits bacteriostatic effects by depriving bacteria of essential iron elements due to its strong iron-binding capacity. Secondly, lactoferrin possesses bactericidal activity via its N-terminal cationic domain, which has unique iron-binding properties that directly kill bacteria. This domain increases bacterial cell membrane permeability, causing lipopolysaccharides to leak from the outer membrane of Gram-negative bacteria. Additionally, lactoferrin can be released through the activation of neutrophils, regulating systemic immune responses and exerting antimicrobial effects. Highly-affinitive lactoferrin receptors have been discovered in various cells, including lymphocytes, monocytes, macrophages, and platelets.


"An overview on in vitro and in vivo antiviral activity of lactoferrin: its efficacy against SARS-CoV-2 infection" proposes that lactoferrin exhibits antiviral activity against various viruses, including SARS-CoV-2. Lactoferrin exerts its effects by binding to host cells and viral particle surface components, involving interactions with host cell heparan sulfate proteoglycans (HSPGs) and viral spike glycoproteins. Studies indicate that lactoferrin demonstrates inhibitory effects on viruses both in vitro and in vivo, including against SARS-CoV-2. Lactoferrin can modulate factors such as viral entry, inflammation, iron balance, oxidative stress, and coagulation. Thus, lactoferrin supplementation may play a positive role in COVID-19 treatment, not only as a standalone therapy for asymptomatic patients but also as an adjunct to standard treatment for symptomatic patients.


"The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria" highlights lactoferrin as a nutritionally significant iron-binding substance found in mammalian milk. It possesses crucial immunological attributes, acting as both an antimicrobial and antiviral agent. Lactoferrin can bind to receptors used by coronaviruses, such as heparan sulfate proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), thus preventing viral entry into cells. Especially during the current COVID-19 pandemic, lactoferrin holds potential preventive and therapeutic value, particularly in forms with enhanced bioavailability like enteric-coated formulations.


Antioxidant and Anticancer Applications:

Lactoferrin and its derivatives have garnered extensive scientific attention as versatile bioactive substances. They showcase exceptional biological properties in areas such as antioxidation, antitumor activity, and immune system regulation, making them considered as both antioxidants and anticancer agents. Concurrently, exogenous treatment with lactoferrin and its derivatives demonstrates potential anticancer effects by effectively suppressing tumor growth and increasing tumor suppression sensitivity. These studies provide robust support for the application of lactoferrin in the field of anticancer research, and significant progress has been made in exploring their mechanisms of action.


"Advances in Research on the Antitumor Effects and Mechanisms of Lactoferrin and Its Derivatives" asserts that lactoferrin exhibits a range of biological functions widely recognized in the scientific community. Notably, it participates in iron storage and transportation while also performing roles such as antimicrobial, antioxidant, anticancer activity, and immune system modulation. Lactoferrin and its derivatives as exogenous treatments effectively inhibit tumor growth and reduce tumor susceptibility. The anticancer effects of lactoferrin are primarily achieved through pathways such as cell membrane disruption, apoptosis induction, cell cycle arrest, and cellular immune responses.


"Investigation and comparison of the anti-tumor activities of lactoferrin, α-lactalbumin, and β-lactoglobulin in A549, HT29, HepG2, and MDA231-LM2 tumor models" focuses on A549, HT29, HepG2, and MDA231-LM2 human tumor cell models, comparing the anticancer effects of lactoferrin, α-lactalbumin, and β-lactoglobulin. The study measures their impact on cell proliferation, migration, and apoptosis in vitro, as well as their effects in murine models carrying tumors. Results reveal that these three proteins to varying degrees inhibit tumor cell survival and migration, achieving anticancer effects by inducing apoptosis. In vivo experiments further confirm the significant impact of lactoferrin and α-lactalbumin on specific tumor model tumor masses. The study also validates the roles of these proteins in modulating apoptosis-related proteins.


"Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action" focuses on the anticancer properties of lactoferrin. Despite advances in cancer treatment, conventional therapies often come with side effects and long-term consequences, lacking selectivity against cancer cells. Natural health products are gaining attention as adjunctive anticancer therapies due to their richness, high bioavailability, safety, low cost, and host immune compatibility. The review emphasizes lactoferrin as an immune defense molecule, which, when orally administered, efficiently converts into L-fucose and exhibits strong selectivity against cancer cells. Lactoferrin regulates various molecular targets related to tumor proliferation, survival, and migration, showcasing a wide range of effects. Notably, while promoting normal cell proliferation and migration, lactoferrin exhibits inhibitory effects on cancer cells and is well-tolerated. By enhancing immune responses, lactoferrin prevents tumor development and inhibits tumor growth. Recent research even suggests that lactoferrin can traverse the blood-brain barrier, indicating its potential in treating brain tumors. This underscores its extensive potential in cancer prevention and treatment, particularly in combination therapies. Lactoferrin's multifaceted actions make it a promising candidate for addressing the challenges of cancer treatment and fostering improved patient outcomes.


"Evaluation of the Anti-Inflammatory and Anti-Oxidative Effects of Therapeutic Human Lactoferrin Fragments" emphasizes the urgency of addressing chronic inflammation, especially in inflammatory diseases such as inflammatory bowel disease. While lactoferrin has been used to treat mild gastrointestinal and skin inflammation, its digested fragments often exhibit enhanced therapeutic properties. The study assessed the anti-inflammatory effects of recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colon fibroblasts and colorectal cancer cells. It revealed that rtHLF4 had a 10-fold higher efficacy in preventing inflammation compared to intact lactoferrin. Through studies on reactive oxygen species (ROS) production, angiogenic activity, and cell proliferation, the research demonstrated the anti-inflammatory and anti-oxidative properties of lactoferrin fragments and the intact protein, enriching the earlier research on their anticancer attributes.


"New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose" discusses the protective effects of lactoferrin following sublethal doses of gamma irradiation in mice. Experimental results showed that lactoferrin significantly increased the survival rate and lifespan of irradiated mice, positively impacting weight loss and organ tissue structure. This study highlights the early therapeutic potential of lactoferrin following radiation exposure.


"Lactoferrin Deficiency Promotes Melanoma Metastasis through Modulation of the Tumor Microenvironment" investigates the impact of lactoferrin deficiency on melanoma cell metastasis. The research discovered that lactoferrin deficiency led to the accumulation of myeloid-derived suppressor cells (MDSCs) in the lung microenvironment, thereby promoting melanoma cell lung metastasis. The study further revealed that lactoferrin, by modulating the TLR9 signaling pathway, influenced the tumor microenvironment to protect the immune system from the effects of cancer metastasis.


"Effect of Lactoferrin on Paraoxonase Activity, Some Acute Phase Proteins and Oxidant/Antioxidant System" focuses on the antioxidant effects of lactoferrin (LF) in the context of liver damage induced by parathion (DZN). The study divided rats into five groups: control, lactoferrin, DZN, DZN + LF, and LF + DZN, to evaluate the impacts of different treatment regimens. By measuring biochemical markers such as nitric oxide (NO), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in liver tissues, along with histopathological examination, the study demonstrated that LF reduced NO and MDA levels, increased GSH-Px activity, and improved liver histopathology under DZN-induced liver damage. These findings indicate that lactoferrin possesses antioxidant properties that can mitigate DZN-induced liver damage.


"Immune Regulation and Gut Microbiota Modulation Applications":The role of lactoferrin in immune regulation and gut microbiota modulation is gaining recognition. Immune regulation and balanced gut microbiota are crucial for maintaining overall health, and lactoferrin's unique effects in these areas are increasingly being unveiled through scientific research.


"Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages" underscores the key role of lactoferrin in the immune defense system. It serves various biological functions beyond its role as an iron storage and transport molecule, including being released during inflammatory conditions and being closely linked to immune modulation. This study, utilizing bovine lactoferrin in M1 macrophages, explored its impact on the expression of major proteins related to iron balance and inflammatory balance. The results indicated that bovine lactoferrin significantly reduced the production of pro-inflammatory cytokines IL-6 and IL-1β by cells and effectively prevented intracellular iron overload. This suggests that lactoferrin can maintain iron balance within cells and holds significance in countering inflammatory states.


"A Critical Review of the Roles of Host Lactoferrin in Immunity" highlights the crucial role of lactoferrin in innate immunity. Lactoferrin is a vital component of innate immunity and acts as a nonspecific defense mechanism that rapidly responds to infections. It can recognize microbial molecules, interact with host cells, and regulate the migration, maturation, and function of immune cells. This article underscores lactoferrin's immunoregulatory properties, which vary based on physiological conditions and may involve competition or collaboration with immune cell receptors. Through a critical analysis of literature data, it reveals the practical application of lactoferrin in immune regulation.


"Bovine lactoferrin and its effects on innate immune cells in a complex milk matrix" elucidates the impact of lactoferrin on innate immune cells and investigates its influence within a complex milk environment. The study reveals that lactoferrin not only affects the biological responses of innate immune cells in both in vitro and in vivo experiments but also modulates cellular immune responses within a milk matrix. This research uncovers lactoferrin's role in immune cells within a complex environment, providing important insights for further understanding its regulatory role in the immune system.


"Human Lactoferrin attracts monocytes and activates monocyte‐derived Dendritic Cells to become mature antigen‐presenting cells" highlights the role of human lactoferrin in the immune system. Recombinant human lactoferrin was found to attract monocytes and induce cell maturation in blood or dendritic cell cultures, evidenced by upregulated specific cell surface markers, pro-inflammatory cytokine production, and enhanced lymphocyte proliferation. In mice, lactoferrin was observed to induce leukocyte aggregation and activation. These results suggest that lactoferrin may play a crucial role in immune cell activation and chemotaxis, potentially influencing both innate and adaptive immune responses.


"Effects of lactoferrin on intestinal flora of metabolic disorder mice" explores how lactoferrin regulates intestinal microbiota to address metabolic disorders. The study found that lactoferrin treatment significantly reduced visceral fat proportion, blood glucose, and lipid levels in high-fat diet mice. Furthermore, lactoferrin treatment altered the composition of gut microbiota, reducing the Firmicutes/Bacteroidetes ratio, increasing beneficial bacteria abundance, and decreasing harmful bacteria. This research indicates that lactoferrin improves metabolic disorder by modulating gut microbiota.


"Influence of milk-derived lactoferrin on intestinal microbial flora in mice" investigates the impact of milk-derived lactoferrin on the gut microbial flora of mice. The results show that an appropriate amount of lactoferrin promotes the growth of beneficial bacteria such as lactobacilli and bifidobacteria while inhibiting the growth of harmful bacteria. The study suggests that milk-derived lactoferrin may have an impact on regulating the gut microbial flora in mice.


Combination Drug Applications:

Lactoferrin plays a crucial role in nanotechnology and combination drug therapies. Future research will further delve into the mechanisms of lactoferrin in areas such as drug delivery and disease treatment, providing valuable guidance for the development of novel drug delivery systems and treatment strategies.


"Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets" addresses how transgenic milk containing recombinant human lactoferrin influences piglet intestinal microbiota. The experiment revealed that piglets fed with transgenic milk containing pure recombinant human lactoferrin exhibited better growth than those fed regular whole milk. Microbiota analysis indicated increased diversity and abundance of beneficial bacteria and reduced abundance of harmful bacteria in the pure recombinant human lactoferrin group. This suggests that recombinant human lactoferrin aids in modulating piglet intestinal microbiota.


"Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment" explores the application of lactoferrin in breast cancer treatment. Researchers applied a combination of drugs within a nano-protein-polysaccharide hybrid system, achieving sequential drug release. The nano-hybrid system significantly enhanced the anticancer effects of the drugs, demonstrating lactoferrin's role in improving intracellular drug absorption.


"Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery" introduces nanostructured lipid carriers (NLCs) as a novel carrier for optimized ocular drug delivery, with lactoferrin loaded into the carriers. These NLCs exhibited high drug loading capacity and controlled release properties for ocular drug delivery. Additionally, NLCs displayed good biocompatibility and adhesion, providing strong support for further clinical applications.


"Different Pathways Mediate Amphotericin-Lactoferrin Drug Synergy in Cryptococcus and Saccharomyces" reveals the differential mechanisms underlying the synergy between lactoferrin and the antifungal drug amphotericin in different fungi. Transcriptome analysis shows that the synergistic mechanisms of lactoferrin and amphotericin vary based on species specificity, possibly due to differences in peptide structures produced by lactoferrin, variations in intracellular targets, and effects on intracellular protein and lipid biosynthesis.


"Effect of Synergistic Action of Bovine Lactoferrin with Antibiotics on Drug Resistant Bacterial Pathogens" investigates the synergistic effect of lactoferrin and antibiotics against multidrug-resistant (MDR) bacterial pathogens. The study background emphasizes the global public health threat posed by MDR bacterial infections, coupled with a reduction in the development of new antibiotics. Research findings demonstrate that the synergistic action of lactoferrin with antibiotics is repeatable and significant, with lactoferrin alone playing a crucial role in inhibiting biofilm formation. These results provide valuable antibacterial potential data for the combined use of lactoferrin and antibiotics against drug-resistant pathogens.


"Drug Repurposing of Lactoferrin Combination in a Nanodrug Delivery System to Combat Severe Acute Respiratory Syndrome Coronavirus-2 Infection" investigates the role of lactoferrin against SARS-CoV-2. Lactoferrin is not only used as a therapeutic agent but is also applied within a nanodrug carrier system. The study uses nitazoxanide as an example to explore the effects of lactoferrin combination. The research reveals that the activity of lactoferrin is enhanced when combined with nitazoxanide, demonstrating potential nanocarrier characteristics. Additionally, spiropyrazoline compounds exhibit antiviral activity.


Applications in Food and Feed Additives:

Research on lactoferrin in the field of food and feed additives is of significant importance, as it has been recognized by the U.S. Food and Drug Administration (FDA) as a safe food additive. Lactoferrin exhibits multiple protective activities, including anti-anemia, anti-inflammatory, antimicrobial, immune-modulating, antioxidant, and anticancer effects, making it an ideal nutritional supplement. Additionally, introducing lactoferrin into genetically modified rice and using it as a feed additive for animal nutrition can enhance antibacterial capabilities and immune characteristics, not only benefiting animal health but also providing a new approach for developing novel feed additives.


"Lactoferrin from Bovine Milk: A Protective Companion for Life" highlights lactoferrin as a multifunctional glycoprotein with a crucial role in host defense. Lactoferrin has been recognized by the FDA as a safe food additive. Upon oral administration, lactoferrin exhibits various important protective activities, including anti-anemia, anti-inflammatory, antimicrobial, immune-modulating, antioxidant, and anticancer effects. This review emphasizes lactoferrin as an ideal nutritional supplement and outlines its numerous benefits upon oral consumption, providing insights into its potential applications in prevention and treatment.


"Porcine lactoferrin expression in transgenic rice and its effects as a feed additive on early weaned piglets" describes the expression of porcine lactoferrin (LF) in transgenic rice and its use as a feed additive for early-weaned piglets. Research results show that expressing porcine lactoferrin in rice through genetic modification can serve as a functional additive to enhance antibacterial capabilities and immune characteristics in early-weaned piglets, without significantly affecting growth performance.


"Interaction Mechanism between Lactoferrin and Other Proteins in Bovine Milk" investigates the interaction mechanism between lactoferrin and other proteins in bovine milk. The study finds that lactoferrin interacts positively with negatively charged proteins in bovine milk, such as casein, osteopontin, β-lactoglobulin, immunoglobulin, and bovine serum albumin. These interactions can influence the biological functions and purification properties of these proteins. The review elucidates the interaction mechanism between lactoferrin and other bovine milk proteins, providing theoretical reference for the development of industrial extraction methods for lactoferrin.


Cosmetic Industry Applications:

"Use of lactoferrin in cosmetic preparations acting against free radicals" highlights the utilization of purified lactoferrin in cosmetic products as an anti-free radical agent. These formulations can be employed to combat skin aging and alleviate free radical damage caused by inflammation or erythema. Lactoferrin, a multifunctional glycoprotein with potent anti-free radical properties, is well-suited for incorporation into cosmetic formulations. These preparations offer promising solutions for addressing skin issues arising from oxidative stress and inflammation. This invention underscores the ability of lactoferrin to serve as an anti-free radical agent and emphasizes its potential application in cosmetic products aimed at maintaining skin health and vitality.


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Lactoferrin from Bovine Milk

Catalog Number

CAS

Grade

Package Size

DXJ0101A-50mg

146897-68-9

≥95%

50mg

DXJ0101A-100mg

146897-68-9

≥95%

100mg

Used as a standard in protein quantification; serves as a negative control in enzyme activity assays.


Lactoferrin from Human Milk

Attribute

Plant-Derived Recombinant Human Milk Lactoferrin

Human Milk Lactoferrin

Specifications

1g 10g 100g

5g 25g 100g

CAS Number

936541-36-5

936541-36-5

Purity

≥95%, SDS-PAGE

≥85% (SDS-PAGE)

Source

Rice Seeds

Human Breast Milk

Appearance

Pink Crystalline Powder

White to Light Red (Powder)

pH Value

5.2-7.2

7.4

Molecular Weight

80kDa

82.4 kDa

Solubility


1 mg/mL, clear to slightly hazy (0.01 M phosphate buffer, 0.0027 M potassium chloride and 0.137 M sodium chloride, pH 7.4, 25 °C)

Intended Use

For research, laboratory, and production purposes only. Bioreagent grade, suitable for cell culture.

Storage Conditions for Human Milk Lactoferrin (Store at 2-8°C)