{{Original research|date=September 2010}}
'''Colostrinin''' (also known as '''CLN''', '''proline-rich polypeptides''' or '''PRP''') is a mixture of proline-rich polypeptides extracted from colostrum from sheep and cows.
==Early work on Colostrinin==
Colostrinin was originally identified by scientists working in Poland in the 1970s.<ref>{{cite journal |last1=Staroscik |first1=K |last2=Janusz |first2=M |last3=Zimecki |first3=M |last4=Wieczorek |first4=Z |last5=Lisowski |first5=J |title=Immunologically active nonapeptide fragment of a proline-rich polypeptide from ovine colostrum: Amino acid sequence and immunoregulatory properties☆ |journal=Molecular Immunology |volume=20 |issue=12 |pages=1277–82 |year=1983 |pmid=6656774 |doi=10.1016/0161-5890(83)90157-8}}</ref> {{Citation needed|reason=The provided reference lists a publication made in 1983, which does not support the claim about 70s|date=July 2017}} Colostrinin is derived from colostrum, which is present in the pre-milk fluid produced from mammary glands in the first few days after parturition. It is also known as proline-rich polypeptides, since sequence analysis of the peptides present in this mixture reveals an unusually high proportion of this amino acid residue. The amino acid compositions of the extracts from ovine, bovine, and human colostrum are very similar.<ref>{{cite journal |last1=Kruzel |first1=Marion L. |last2=Janusz |first2=Maria |last3=Lisowski |first3=Jozef |last4=Fischleigh |first4=Robert V. |last5=Georgiades |first5=Jerzy A. |title=Towards an Understanding of Biological Role of Colostrinin Peptides |journal=Journal of Molecular Neuroscience |volume=17 |issue=3 |pages=379–89 |year=2001 |pmid=11859934 |doi=10.1385/JMN:17:3:379|s2cid=29568634 }}</ref> Colostrinin was first characterized in animal and in-vitro studies as a substance that generally stimulates the immune response.<ref>{{cite journal |last1=Janusz |first1=M |last2=Lisowski |first2=J |title=Proline-rich polypeptide (PRP)--an immunomodulatory peptide from ovine colostrum |journal=Archivum Immunologiae et Therapiae Experimentalis |volume=41 |issue=5–6 |pages=275–9 |year=1993 |pmid=8010865}}</ref>
==Preparation and synthesis==
Colostrinin is obtained from bovine colostrum by alcohol extraction and filtration by a patented method.<ref>{{cite journal |last1=Kruzel |first1=Marian L. |last2=Polanowski |first2=Antoni |last3=Wilusz |first3=Tadeusz |last4=Sokołowska |first4=Agata |last5=Pacewicz |first5=Magdalena |last6=Bednarz |first6=Renata |last7=Georgiades |first7=Jerzy A. |title=The Alcohol-Induced Conformational Changes in Casein Micelles: A New Challenge for the Purification of Colostrinin |journal=The Protein Journal |volume=23 |issue=2 |pages=127–33 |year=2004 |pmid=15106878 |doi=10.1023/B:JOPC.0000020079.76155.9d|s2cid=40619314 }}</ref> Colostrinin largely consists of a mixture of at least 32 peptides ranging in size from 0.5 to 3 kDa.<ref>{{cite journal |last1=Rattray |first1=M |title=Technology evaluation: colostrinin, ReGen |journal=Current Opinion in Molecular Therapeutics |volume=7 |issue=1 |pages=78–84 |year=2005 |pmid=15732533}}</ref> Most of the peptides appear to be derived from proteolytic processing of the milk proteins β-casein and a β-casein homolog.
==Potential Health benefits==
PRP-rich preparations from bovine colostrum have shown possible efficacy against various illnesses including neurodegenerative diseases (such as Alzheimer's), viral infections, and ailments characterized by an overactive immune system, such as allergies, asthma and autoimmune diseases.<ref>{{Cite journal|last1=Zabłocka|first1=Agnieszka|last2=Sokołowska|first2=Agata|last3=Macała|first3=Józefa|last4=Bartoszewska|first4=Magdalena|last5=Mitkiewicz|first5=Małgorzata|last6=Janusz|first6=Maria|last7=Wilusz|first7=Tadeusz|last8=Polanowski|first8=Antoni|date=June 2020|title=Colostral Proline-Rich Polypeptide Complexes. Comparative Study of the Antioxidant Properties, Cytokine-Inducing Activity, and Nitric Oxide Release of Preparations Produced by a Laboratory and a Large-Scale Method|journal=International Journal of Peptide Research and Therapeutics|language=en|volume=26|issue=2|pages=685–694|doi=10.1007/s10989-019-09876-6|issn=1573-3149|doi-access=free}}</ref> Some recent research has also indicated possible efficacy in combating obesity.<ref>{{cite journal |last1=Szaniszlo |first1=P |last2=German |first2=P |last3=Hajas |first3=G |last4=Saenz |first4=D |last5=Woodberry |first5=M |last6=Kruzel |first6=M |last7=Boldogh |first7=I |title=Effects of Colostrinin™ on gene expression-transcriptomal network analysis |journal=International Immunopharmacology |volume=9 |issue=2 |pages=181–93 |year=2009 |pmid=19015048 |doi=10.1016/j.intimp.2008.10.022|hdl=2437/208248 |hdl-access=free }}</ref>
===Allergy=== A study published online in March 2008 showed that Colostrinin is non-allergenic and can prevent allergic inflammation due to common indoor and outdoor allergens.<ref>{{cite journal |last1=Boldogh |first1=Istvan |last2=Aguilera-Aguirre |first2=Leopoldo |last3=Bacsi |first3=Attila |last4=Choudhury |first4=Barun K. |last5=Saavedra-Molina |first5=Alfredo |last6=Kruzel |first6=Marian |title=Colostrinin Decreases Hypersensitivity and Allergic Responses to Common Allergens |journal=International Archives of Allergy and Immunology |volume=146 |issue=4 |pages=298–306 |year=2008 |pmid=18367843 |doi=10.1159/000121464|s2cid=5430099 }}</ref> The study used a well characterized mouse model of allergic airway inflammation. Colostrinin (given orally, intranasally or intraperitoneally) significantly decreased IgE/IgG1 production, airway eosinophilia, mucin production and hypersensitivity induced by allergenic extracts from ragweed pollen and house dust mites. In contrast, colostrum induced positive inflammatory responses.
===Cognition and dementia=== Colostrinin has possible efficacy in Alzheimer's disease and as a cognitive enhancer.<ref name="Pmid_a">{{cite journal |last1=Leszek |first1=J |last2=Inglot |first2=AD |last3=Janusz |first3=M |last4=Lisowski |first4=J |last5=Krukowska |first5=K |last6=Georgiades |first6=JA |title=Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study |journal=Archivum Immunologiae et Therapiae Experimentalis |volume=47 |issue=6 |pages=377–85 |year=1999 |pmid=10608295}}</ref><ref>{{cite journal |last1=Kubis |first1=AM |last2=Janusz |first2=M |title=Alzheimer's disease: new prospects in therapy and applied experimental models |journal=Postepy Higieny I Medycyny Doswiadczalnej |volume=62 |pages=372–92 |year=2008 |pmid=18688208}}</ref>
A placebo-controlled clinical trial with Colostrinin in 106 people with Alzheimer's over 30 weeks was completed in 2002 and the results appeared to demonstrate efficacy in a significant proportion of patients treated.<ref name="Pmid">{{cite journal |last1=Bilikiewicz |first1=A |last2=Gaus |first2=W |title=Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease |journal=Journal of Alzheimer's Disease |volume=6 |issue=1 |pages=17–26 |year=2004 |pmid=15004324|doi=10.3233/JAD-2004-6103 }}</ref> The results showed that approximately 40% of patients on Colostrinin were stabilized or improved after 15 weeks of therapy, based on an Analysis of Overall Response. 33% of patients continued to show stabilization or improvement after 30 weeks of treatment, although levels of benefit were slightly higher at the 15-week stage of the trial. The dosage regimen used for the trial was 100 micrograms of Colostrinin administered every second day for three weeks followed by a two-week period without Colostrinin.
A 2010 study demonstrated that Colostrinin significantly relieved amyloid-beta (Aß)-induced cytotoxicity, alleviated the effect of Aß-induced cytotoxicity and caused a significant reduction in the elevated levels of the antioxidant enzyme SOD1.<ref name="FroudWardhaugh2010">{{cite journal|last1=Froud|first1=Kristina E.|last2=Wardhaugh|first2=Tina|last3=Banks|first3=Duncan|last4=Saffrey|first4=M. Jill|last5=Stewart|first5=Michael G.|title=Colostrinin™ Alleviates Amyloid-β Induced Toxicity in Rat Primary Hippocampal Cultures|journal=Journal of Alzheimer's Disease|volume=20|issue=2|year=2010|pages=423–426|issn=1875-8908|doi=10.3233/JAD-2010-1382|pmid=20164569|url=http://oro.open.ac.uk/20163/1/Froud_et_al.pdf}}</ref>
Another study showed that Colostrinin induces neurite outgrowth of pheochromocytoma cells and inhibits beta amyloid-induced apoptosis.<ref>{{cite journal |last1=Bacsi |first1=A |last2=Woodberry |first2=M |last3=Kruzel |first3=M |last4=Boldogh |first4=I |title=Colostrinin delays the onset of proliferative senescence of diploid murine fibroblast cells |journal=Neuropeptides |volume=41 |issue=2 |pages=93–101 |year=2007 |pmid=17300837 |doi=10.1016/j.npep.2006.12.004|s2cid=32879809 }}</ref>
There were also studies of the Colostrinin components and their possible effect on aggregation of amyloid beta (Abeta1-42). Results presented suggest that NP - Colostrinin component, can directly interact with amyloid beta, inhibit its aggregation and disrupt existing aggregates acting as a beta sheet breaker and reduce toxicity induced by aggregated forms of Abeta.<ref>{{cite journal |last1=Janusz |first1=Maria |last2=Woszczyna |first2=Mirosław |last3=Lisowski |first3=Marek |last4=Kubis |first4=Adriana |last5=MacAła |first5=JóZefa |last6=Gotszalk |first6=Teodor |last7=Lisowski |first7=Józef |title=Ovine colostrum nanopeptide affects amyloid beta aggregation |journal=FEBS Letters |volume=583 |issue=1 |pages=190–6 |year=2009 |pmid=19084010 |doi=10.1016/j.febslet.2008.11.053|s2cid=32036747 |doi-access=free |bibcode=2009FEBSL.583..190J }}</ref>
Another study in day-old domestic chicks showed enhancement of long-term memory retention.<ref>{{cite journal |last1=Stewart |first1=M |last2=Banks |first2=D |title=Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm |journal=Neurobiology of Learning and Memory |volume=86 |issue=1 |pages=66–71 |year=2006 |pmid=16473531 |doi=10.1016/j.nlm.2005.12.011|s2cid=32365343 }}</ref>
A randomized, double-blind, placebo-controlled trial from 2023 showed that daily use of Colostrinin improved scores on 2 of 5 cognitive tests in adults of various ages in Poland over a 4-month period.<ref>{{cite journal | pmc=10002942 | date=2023 | last1=Banasiak-Cieślar | first1=H. | last2=Wiener | first2=D. | last3=Kuszczyk | first3=M. | last4=Dobrzyńska | first4=K. | last5=Polanowski | first5=A. | title=Proline-rich polypeptides (Colostrinin®/COLOCO ®) modulate BDNF concentration in blood affecting cognitive function in adults: A double-blind randomized placebo-controlled study | journal=Food Science & Nutrition | volume=11 | issue=3 | pages=1477–1485 | doi=10.1002/fsn3.3187 | pmid=36911821 }}</ref>
===Anti-aging potential===
Colostrinin affects the early stages of Vitamin D3-induced phenotypic (CD11b and CD14) and functional (phagocytic) differentiation/maturation of monocytes/macrophages. When Colostrinin was administered to the cells after treatment with Vitamin D3, no attenuation of the differentiation/maturation process of the HL-60 cells was observed.<ref>{{cite journal |last1=Kubis |first1=A |last2=Marcinkowska |first2=E |last3=Janusz |first3=M |last4=Lisowski |first4=J |title=Studies on the mechanism of action of a proline-rich polypeptide complex (PRP): Effect on the stage of cell differentiation |journal=Peptides |volume=26 |issue=11 |pages=2188–92 |year=2005 |pmid=15904991 |doi=10.1016/j.peptides.2005.04.001|s2cid=40152083 }}</ref>
An in-vitro study completed in 2005 showed that Colostrinin can increase the lifespan of cells isolated from inbred mice predisposed to premature aging and death.<ref>I. Boldogh; A. Bacsi; L. Agulera-Aguirre; P. German; M. Kruzel; Colostrinin Increases the Lifespan and Neurological Performance of Mice, 03, 2008.</ref>{{Unreliable medical source|date=March 2011}}
A 2006 study published in the Journal of Experimental Therapeutics and Oncology indicated that Colostrin reduces the mutation frequency in the DNA of cells.<ref>{{cite journal |last1=Bacsi |first1=A |last2=Aguilera-Aguirre |first2=L |last3=German |first3=P |last4=Kruzel |first4=ML |last5=Boldogh |first5=I |title=Colostrinin decreases spontaneous and induced mutation frequencies at the hprt locus in Chinese hamster V79 cells |journal=Journal of Experimental Therapeutics & Oncology |volume=5 |issue=4 |pages=249–59 |year=2006 |pmid=17024966}}</ref> Such DNA damage is implicated in the general process of aging. The study, which was performed in both hamster and human cells, looked at the effect of Colostrinin on the frequency of defined DNA mutations in these cells as they occur naturally and when induced by various known chemical or physical agents. In cells stressed oxidatively, Colostrinin reduced the frequency of mutation induced by reactive oxygen species (ROS) to nearly background levels in a dose-dependent manner. Likewise, Colostrinin reduced the frequency of mutation caused by two mutagenic agents, methyl methane sulfonate and mitomycin-C, the latter often used in cancer chemotherapy. Notably Colostrinin decreased UVA and UVB radiation induced mutation frequency. These damaging radiations are a natural part of sunlight. UVA radiation plays a role in the induction of melanoma and UVB radiation is the primary cause of squamous cell carcinomas. It is suggested that the antimutagenic properties of Colostrinin are achieved via multiple mechanisms - by decreasing intracellular levels of ROS and so preventing DNA damage and by increasing the efficiency of natural DNA repair mechanisms.
==Toxicity==
There has been very little mention of toxicity in most published animal studies using Colostrinin, which may suggest that it exhibits low toxicity. Generally, treatment with Colostrinin in clinical studies has been well tolerated<ref name="Pmid" /> by both animals and humans, with any side-effects being mild and transient.<ref name="Pmid_a" />
==Use by humans==
Tablets or capsules containing Colostrinin are available in many countries in the world and are sold as an OTC dietary supplement under various trade names.
==References== {{reflist}} Reference 10 citation: * {{cite journal | last1 = Froud | first1 = Kristina E. | last2 = Wardhaugh | first2 = Tina | last3 = Banks | first3 = Duncan | last4 = Saffrey | first4 = M. Jill | last5 = Stewart | first5 = Michael G. | year = 2010 | title = Colostrinin™ Alleviates Amyloid-β Induced Toxicity in Rat Primary Hippocampal Cultures | url = http://oro.open.ac.uk/20163/1/Froud_et_al.pdf| journal = Journal of Alzheimer's Disease | volume = 20 | issue = 2| pages = 423–426 | doi = 10.3233/JAD-2010-1382 | pmid = 20164569 }}
Category:Dietary supplements