Corresponding author: Hendris Wongso ( hendriswongso@batan.go.id ) Academic editor: Georgi Momekov
© 2021 Crhisterra Ellen Kusumaningrum, Eva Maria Widyasari, Maula Eka Sriyani, Hendris Wongso.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Kusumaningrum CE, Widyasari EM, Sriyani ME, Wongso H (2021) Pharmacological activities and potential use of bovine colostrum for peptide-based radiopharmaceuticals: A review. Pharmacia 68(2): 471-477. https://doi.org/10.3897/pharmacia.68.e65537
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Bovine colostrum (BC) is the initial milk produced by cows after giving birth. It has been used to treat human diseases, such as infections, inflammations, and cancers. Accumulating evidence suggests that bovine lactoferrin and bovine antibodies seem to be the most important bioactive constituents in BC. Thus, BC has also been reviewed for its potential to deliver short-term protection against coronavirus disease 2019 (COVID-19). In addition, it can potentially be explored as a precursor for peptide-based radiopharmaceuticals. To date, several bioactive peptides have been isolated from BC, including casocidin-1, casecidin 15 and 17, isracidin, caseicin A, B, and C. Like other peptides, bioactive peptides derived from BC could be used as a valuable precursor for radiopharmaceuticals either for diagnosis or therapy purposes. This review provides bovine colostrum’s biological activities and a perspective on the potential use of peptides from BC for developing radiopharmaceuticals in nuclear medicine.
Antibodies, biological activities, bovine colostrum, peptides, radiopharmaceuticals
Bovine colostrum (BC) is the milky fluid secreted by cows in the first few days after giving birth that has important potential to promote beneficial effects through the improvement of immunological functions. In dairy cows, bovine antibodies are actively transported from the mammary epithelial cells to the mammary gland by receptor-mediated mechanisms, and are present in high concentration in colostrum (
As crucial as for calves, BC is also one of the valuable components with rich health benefits for humans and has been used as a dietary supplement (
The biological effect of BC immunoglobulins on human health, especially for immune functions, has been widely studied, and continues to be an area of interest. Accumulating evidence suggests that BC IgG could bind to some variety of infectious bacteria, viruses, and allergens (
Prior to discovering antibiotics, BC has been employed to cure numerous ailments, including bacteria-associated infections and physical illness linked with immunity (
To combat infectious diseases, several antimicrobial compounds have been discovered so far (
A study by Anand and colleagues demonstrated that bLf could interact with parasite-host cells, such as red blood cells and macrophages in specific mechanisms depending on the level of iron saturation of lactoferrin. The authors revealed that incubation of iron saturated lactoferrin with bLf increases the phagocytic activity, production of reactive oxygen species, and Toll-like receptor expression (
It was found that skimmed and concentrated late bovine colostrum that contains a high concentration of IgG exhibits anti-human rotavirus (HRV) activity in in vitro model, and therefore may be potentially used as a natural treatment, especially in immunocompromised subjects, such as children and the elderly (
Some reports show that bLf can exert anti-inflammatory effects in numerous preclinical and clinical studies (
In combination with glutamine, BC demonstrates superior activity in reducing the non-steroidal anti-inflammatory drug (NSAID)-induced intestinal injury and bacterial translocation in animal models compared to the administration of BC or glutamine alone (
Cancer is one of the significant public health concerns in global societies with high unmet medical needs (Wongso et al. 2013;
BC contains two significant families of protein, namely caseins and whey proteins. Lactoferrin, a globular glycoprotein with a molecular mass of approximately 80 kDa is one of the bioactive substances in caseins, and has been investigated for its anti-inflammatory, antioxidant, and anticancer properties (
In a different study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay suggested that treatment with 500 µg/ml of isolated lactoferrin from bovine milk resulted in a very substantial reduction of the oesophageal cancer cell line (KYSE-30) by 53% and 80% after 20 and 62 hours, respectively, with no side effect on surrounding normal cells (
Although oral delivery provides the most favourable method for supplementing bLf, the bioavailability of orally administered bLf suffers from a number of factors associated with protein absorption (
In recent years, the importance of naturally occurring peptides in the pharmaceutical arena is rising rapidly. Several peptides with various biological activities have been isolated from enzymatic hydrolysis of colostrum and milk-derived proteins in vitro and in vivo gastrointestinal digest. These peptides possess a wide range of health benefits such as antimicrobial, antithrombotic, opioid-like, immunomodulatory, and antihypertensive. It is worth noting that the majority of bioactive peptides are originated from caseins, whereas only a few peptides could be obtained from whey proteins (
In nuclear medicine, the use of peptide-based radiopharmaceuticals (radiopeptides) has proved useful for diagnosis and therapy of many diseases, in particular cancers (
To date, numerous bioactive peptides have been isolated from bovine milk, such as casocidin-1, casecidin 15 and 17, isracidin, caseicin A, B, and C. Casocidin-1 was isolated and identified by Zucht et al. as a cationic biopeptide from acidified bovine milk. This peptide showed potent antibacterial activity against Staphylococcus carnosus and Escherichia coli (
Some methods have been used to label peptides with radionuclides, including the direct introduction of radioactive atoms (direct radiolabelling) and indirect labelling using bifunctional chelating (BFC) agents (
Furthermore, labelling of peptides can be performed via radioactive halogen isotopes, such as fluorine-18, bromine-76, iodine-131, and astatine-211 (
Some clinically relevant radionuclides that could be used for labelling naturally occurring peptides either for diagnosis or therapy purposes are summarized in Table
Representative radionuclides used for peptide labelling and their physical parameters.
Radionuclide | Half-life (t1/2) | Type of Emission |
---|---|---|
Technetium-99m (99mTc) | 6.0 h | Υ |
Gallium-68 (68Ga) | 67.7 min | β+, EC |
Iodine-123 (123I) | 13.2 h | EC, Υ |
Iodine-124 (124I) | 4.2 d | β+, EC |
Iodine-125 (125I) | 59.4 d | EC, Υ |
Iodine-131 (131I) | 8.0 d | β-, Υ |
Scandium-44 (44Sc) | 4.0 h | β+ |
Copper-64 (64Cu) | 12.7 h | β+, EC, β- |
Bromine-76 | 16.2 h | β+, EC |
Fluorine-18 (18F) | 109.8 min | β+, EC |
Carbon-11 (11C) | 20.4 min | β+, EC |
Astatine-211 | 7.2 h | α, EC |
Zirconium-89 | 78.4 h | β+, EC |
Yttrium-90 | 64.1 h | β- |
Lutetium-177 | 159.4 h | β- |
BC is considered a rich source of bioactive constituents that possesses several pharmacological activities such as anti-infective, anti-inflammatory, and anticancer. Until recently, BC has been used as a nutraceutical (a compound that is used for both food and medical remedies). Although bioactive peptides have been recognized as a privileged precursor for peptide-based radiopharmaceuticals eligible for detection and treatment of various diseases, the use of peptides from BC remains largely unexplored. Therefore, in-depth studies and novel strategies should be implemented to explore the role of bovine peptides and to achieve BC-based peptides application in clinical settings, especially in nuclear medicine.