Anti-cancer |
Glioblastoma |
bLF blocked the migration of human glioblastoma cell lines by reversing epithelial-to-mesenchymal transition-like processes and inhibiting the IL-6/STAT3 axis. |
(Cutone et al., 2020aCutone, A., Colella, B., Pagliaro, A., Rosa, L., Lepanto, M. S., Bonaccorsi di Patti, M. C., Valenti, P., Di Bartolomeo, S., & Musci, G. (2020a). Native and iron-saturated bovine lactoferrin differently hinder migration in a model of human glioblastoma by reverting epithelial-to-mesenchymal transition-like process and inhibiting interleukin-6/STAT3 axis. Cellular Signalling, 65, 109461. http://dx.doi.org/10.1016/j.cellsig.2019.109461. PMid:31678680. http://dx.doi.org/10.1016/j.cellsig.2019...
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Lung Adenocarcinoma |
A novel human recombinant LF inhibited lung adenocarcinoma cell growth and migration with no cytotoxic effect on normal human epithelial cells. |
(Olszewska et al., 2021Olszewska, P., Pazdrak, B., & Kruzel, M. L. (2021). A novel human recombinant lactoferrin inhibits lung adenocarcinoma cell growth and migration with no cytotoxic effect on normal human epithelial cells. Archivum Immunologiae et Therapiae Experimentalis, 69(1), 33. http://dx.doi.org/10.1007/s00005-021-00637-2. PMid:34748082. http://dx.doi.org/10.1007/s00005-021-006...
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Breast Cancer |
Lactoferricin B triggered mitochondrial membrane depolarization and elevated cytoplasmic calcium levels in MCF-7 cells. |
(Guerra et al., 2019Guerra, J. R., Cárdenas, A. B., Ochoa-Zarzosa, A., Meza, J. L., Umaña Pérez, A., Fierro-Medina, R., Rivera Monroy, Z. J., & García Castañeda, J. E. (2019). The tetrameric peptide LfcinB (20-25) 4 derived from bovine lactoferricin induces apoptosis in the MCF-7 breast cancer cell line. RSC Advances, 9(36), 20497-20504. http://dx.doi.org/10.1039/C9RA04145A. PMid:35515557. http://dx.doi.org/10.1039/C9RA04145A...
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Prostate Adenocarcinoma Cell |
bLF inhibited proliferation, induced apoptosis, intracellular acidification and disrupted lysosomal acidification only in highly metastatic cancer cell lines, whereas BJ-5ta cells were insensitive to bLF. |
(Guedes et al., 2018Guedes, J. P., Pereira, C. S., Rodrigues, L. R., & Côrte-Real, M. (2018). Bovine milk lactoferrin selectively kills highly metastatic prostate cancer PC-3 and osteosarcoma MG-63 cells in vitro. Frontiers in Oncology, 8, 200. http://dx.doi.org/10.3389/fonc.2018.00200. PMid:29915723. http://dx.doi.org/10.3389/fonc.2018.0020...
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Colon Cancer |
bLF played a role in the protective mucus barrier that covers the intestinal epithelium. |
(Tanaka et al., 2021Tanaka, H., Gunasekaran, S., Saleh, D. M., Alexander, W. T., Alexander, D. B., Ohara, H., & Tsuda, H. (2021). Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer. Biochemistry and Cell Biology, 99(1), 159-165. http://dx.doi.org/10.1139/bcb-2020-0087. PMid:32905707. http://dx.doi.org/10.1139/bcb-2020-0087...
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Anti-viral |
COVID-19 |
The binding of bLF to heparan sulfate proteoglycans blocked the attachment of the virus to the host cell, while HSPG mimetic heparin to antagonize the anti-viral activity of bLF. |
(Hu et al., 2021Hu, Y., Meng, X., Zhang, F., Xiang, Y., & Wang, J. (2021). The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor. Emerging Microbes & Infections, 10(1), 317-330. http://dx.doi.org/10.1080/22221751.2021.1888660. PMid:33560940. http://dx.doi.org/10.1080/22221751.2021....
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SARS-CoV-2 |
bLF interacts with pepsin during digestion and releases LF B17-41 with moderate anti-SARS-CoV-2 viral activity |
(Wotring et al., 2022Wotring, J. W., Fursmidt, R., Ward, L., & Sexton, J. Z. (2022). Evaluating the in vitro efficacy of bovine lactoferrin products against SARS-CoV-2 variants of concern. Journal of Dairy Science, 105(4), 2791-2802. http://dx.doi.org/10.3168/jds.2021-21247. PMid:35221061. http://dx.doi.org/10.3168/jds.2021-21247...
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Anti-inflammatory |
Acute Kidney Injury |
Camel milk LF protected the kidney from 5-fluorouracil-induced inflammation and oxidative damage, while scavenging ROS, inhibiting MAPKs and NF-κB and activating the PI3K/Akt/eNOS pathway. |
(Arab et al., 2018Arab, H. H., Salama, S. A., & Maghrabi, I. A. (2018). Camel milk ameliorates 5-fluorouracil-induced renal injury in rats: targeting MAPKs, NF-κB and PI3K/Akt/eNOS pathways. Cellular Physiology and Biochemistry, 46(4), 1628-1642. http://dx.doi.org/10.1159/000489210. PMid:29694984. http://dx.doi.org/10.1159/000489210...
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Enteritis |
In mouse model, by regulating the expression of PPAR-γ, PFKFB3 and NF-κB genes and proteins, apo-LF suppressed colonic mucosal inflammation and repaired mucosal damage. |
(Fan et al., 2022Fan, L. L., Yao, Q. Q., Wu, H. W., Wen, F., Wang, J. Q., Li, H. Y., & Zheng, N. (2022). Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice. Journal of Dairy Science, 105(6), 4791-4803. http://dx.doi.org/10.3168/jds.2021-21428. PMid:35379462. http://dx.doi.org/10.3168/jds.2021-21428...
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Arthritis and Air Pouch Edema |
After internalization of LF into monocytes, LF in camel milk inhibited the activation of NF-κB, thereby inhibiting the production of pro-inflammatory cytokines. |
(Arab et al., 2017Arab, H. H., Salama, S. A., Abdelghany, T. M., Omar, H. A., Arafa, E.-S. A., Alrobaian, M. M., & Maghrabi, I. A. (2017). Camel milk attenuates rheumatoid arthritis via inhibition of mitogen activated protein kinase pathway. Cellular Physiology and Biochemistry, 43(2), 540-552. http://dx.doi.org/10.1159/000480527. PMid:28930753. http://dx.doi.org/10.1159/000480527...
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Anti-bacterial |
Burkholderia |
A construct combining two antimicrobial structural domains of bLF lactoferrampin265-284 and lactoferricin17-30 resulted in disruption of the bacterial plasma membrane and subsequent leakage of intracellular nucleotides leading to cell death. |
(Kanthawong et al., 2014Kanthawong, S., Puknun, A., Bolscher, J. G., Nazmi, K., van Marle, J., de Soet, J. J., Veerman, E. C., Wongratanacheewin, S., & Taweechaisupapong, S. (2014). Membrane-active mechanism of LFchimera against Burkholderia pseudomallei and Burkholderia thailandensis. Biometals, 27(5), 949-956. http://dx.doi.org/10.1007/s10534-014-9760-5. PMid:24961697. http://dx.doi.org/10.1007/s10534-014-976...
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Vibrio Cholerae |
bLF interacts directly with the negatively charged components of the microbial membrane, inducing changes in their permeability by dispersing them. |
(Acosta-Smith et al., 2018Acosta-Smith, E., Viveros-Jimenez, K., Canizalez-Roman, A., Reyes-Lopez, M., Bolscher, J. G., Nazmi, K., Flores-Villaseñor, H., Alapizco-Castro, G., de la Garza, M., Martínez-Garcia, J. J., Velazquez-Roman, J., & Leon-Sicairos, N. (2018). Bovine lactoferrin and lactoferrin-derived peptides inhibit the growth of Vibrio cholerae and other Vibrio species. Frontiers in Microbiology, 8, 2633. http://dx.doi.org/10.3389/fmicb.2017.02633. PMid:29375503. http://dx.doi.org/10.3389/fmicb.2017.026...
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Neisseria Meningitidis |
The C-lobe of hLF interacts with the bilobed outer membrane of Gram-negative bacteria at two different sites of lipoprotein, where binding of hLF prevents iron uptake or disrupts the protective membrane-bound lipoprotein against the cationic antimicrobial peptide. |
(Ostan et al., 2017Ostan, N. K., Yu, R.-H., Ng, D., Lai, C. C.-L., Pogoutse, A. K., Sarpe, V., Hepburn, M., Sheff, J., Raval, S., Schriemer, D. C., Moraes, T. F., & Schryvers, A. B. (2017). Lactoferrin binding protein B-a bi-functional bacterial receptor protein. PLoS Pathogens, 13(3), e1006244. http://dx.doi.org/10.1371/journal.ppat.1006244. PMid:28257520. http://dx.doi.org/10.1371/journal.ppat.1...
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Aflatoxin M1 |
LF resulted in a reduction in afm1-induced intestinal permeability, increased expression of claudin-3, ocludin and ZO-1 proteins, and repair of the damaged intestinal barrier. |
(Gao et al., 2021Gao, Y.-N., Li, S.-L., Yang, X., Wang, J.-Q., & Zheng, N. (2021). The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity. International Journal of Molecular Sciences, 23(1), 289. http://dx.doi.org/10.3390/ijms23010289. PMid:35008712. http://dx.doi.org/10.3390/ijms23010289...
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Cronobacter and Pseudomonas spp. |
bLF inhibited the growth of sepsis-causing microorganisms in recombinant IMF and bacteria. |
(Sawale et al., 2022Sawale, M., Ozadali, F., Valentine, C. J., Benyathiar, P., Drolia, R., & Mishra, D. K. (2022). Impact of bovine lactoferrin fortification on pathogenic organisms to attenuate the risk of infection for infants. Food Control, 139, 109078. http://dx.doi.org/10.1016/j.foodcont.2022.109078. http://dx.doi.org/10.1016/j.foodcont.202...
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Salmonella enterica and E. coli O157:H7 |
The growth of E. coli O157:H7 was significantly reduced at LF concentrations greater than 14.05 mg/mL and the growth of S. enterica was reduced at LF concentrations equal to or greater than 112.5 mg/mL. |
(Biernbaum et al., 2021Biernbaum, E. N., Gnezda, A., Akbar, S., Franklin, R., Venturelli, P. A., & McKillip, J. L. (2021). Lactoferrin as an antimicrobial against Salmonella enterica and Escherichia coli O157: H7 in raw milk. JDS Communications, 2(3), 92-97. http://dx.doi.org/10.3168/jdsc.2020-0030. PMid:36339505. http://dx.doi.org/10.3168/jdsc.2020-0030...
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Anti-parasitic |
Amoebiasis |
bLF-derived peptides were effective in resolving murine intestinal amoebiasis in vitro. |
(Díaz-Godínez et al., 2019Díaz-Godínez, C., González-Galindo, X., Meza-Menchaca, T., Bobes, R. J., de la Garza, M., León-Sicairos, N., Laclette, J. P., & Carrero, J. C. (2019). Synthetic bovine lactoferrin peptide Lfampin kills Entamoeba histolytica trophozoites by necrosis and resolves amoebic intracecal infection in mice. Bioscience Reports, 39(1), BSR20180850. http://dx.doi.org/10.1042/BSR20180850. PMid:30429239. http://dx.doi.org/10.1042/BSR20180850...
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Osteogenesis |
Osteogenic Factor |
By activating Smad2/3 and p38 MAPK, bLF enhanced osteoblast differentiation from MSCs, resulting in increased transcriptional activity of Runx2. bLF treatment enhanced osteoblast differentiation and mineralized nodule formation, as well as the repair of bone defects in vitro. |
(Inubushi et al., 2020Inubushi, T., Kosai, A., Yanagisawa, S., Chanbora, C., Miyauchi, M., Yamasaki, S., Sugiyama, E., Ishikado, A., Makino, T., & Takata, T. (2020). Bovine lactoferrin enhances osteogenesis through Smad2/3 and p38 MAPK activation. Journal of Oral Biosciences, 62(2), 147-154. http://dx.doi.org/10.1016/j.job.2020.05.001. PMid:32464258. http://dx.doi.org/10.1016/j.job.2020.05....
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Enzyme activity |
DNA Binding |
LF has a sequence similar to ribonuclease A and has DNA-binding properties that allow it to act in the transcriptional activation of specific DNA sequences and also as a mediator of signal transduction. |
(Brandl et al., 2010Brandl, N., Zemann, A., Kaupe, I., Marlovits, S., Huettinger, P., Goldenberg, H., & Huettinger, M. (2010). Signal transduction and metabolism in chondrocytes is modulated by lactoferrin. Osteoarthritis and Cartilage, 18(1), 117-125. http://dx.doi.org/10.1016/j.joca.2009.08.012. PMid:19747587. http://dx.doi.org/10.1016/j.joca.2009.08...
; García-Montoya et al., 2012García-Montoya, I. A., Cendón, T. S., Arévalo-Gallegos, S., & Rascón-Cruz, Q. (2012). Lactoferrin a multiple bioactive protein: an overview. Biochimica et Biophysica Acta, 1820(3), 226-236. http://dx.doi.org/10.1016/j.bbagen.2011.06.018. PMID: 21726601. http://dx.doi.org/10.1016/j.bbagen.2011....
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Nerve Function Regulation |
Neural Development and Cognition |
LF improved neurodevelopment, cognition, and memory in piglets through upregulation of brain-derived neurotrophic factor signaling pathways. |
(Chen et al., 2015Chen, Y., Zheng, Z., Zhu, X., Shi, Y., Tian, D., Zhao, F., Liu, N., Hüppi, P. S., Troy, F. A. 2nd., & Wang, B. (2015). Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation. Molecular Neurobiology, 52(1), 256-269. http://dx.doi.org/10.1007/s12035-014-8856-9. PMid:25146846. http://dx.doi.org/10.1007/s12035-014-885...
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