KPV is a tripeptide made of three amino acids – lysine, proline and valine – that forms the end of the hormone α-MSH. It keeps its anti-inflammatory effects but, unlike α-MSH, does not trigger pigment production. It is studied mainly in inflammatory bowel diseases such as ulcerative colitis, though so far only in cells and mice.[1]
KPV at a glance
- Sequence: Lys-Pro-Val (amino acids 11–13 of the hormone α-MSH), molecular weight about 342 g/mol.
- Entry into cells: via the PepT1 transporter, which is increased in inflamed intestinal mucosa.[2]
- Main effect in studies: dampening of the NF-κB inflammatory pathway.
- Status: no clinical studies in humans, not an approved medicine.
Where does KPV come from?
α-MSH (alpha-melanocyte-stimulating hormone) is known mainly for triggering melanin production in the skin. As early as the 1980s, however, scientists noticed that it strongly dampens inflammation. When they investigated which part of the molecule was responsible, they found that even the last three amino acids – Lys-Pro-Val – keep the anti-inflammatory effect.[1] This short segment does not activate the pigmentation receptor, which makes it “cleaner” for inflammation research than the whole hormone.
How does KPV dampen inflammation?
The main target is the transcription factor NF-κB – the “master switch” of inflammation in the cell, which triggers the production of inflammatory cytokines. KPV prevents its activation and also the activation of MAP kinase pathways, so cells release fewer inflammatory signals.[2] In a mouse study the effect was not fully dependent on the classic melanocortin receptor MC1R, which suggests that KPV may also act inside the cell.[3]
Why is KPV studied in gut inflammation?
The key is the PepT1 transporter. This protein carries short peptides from the gut into mucosal cells, and there is little of it in a healthy colon. In chronic gut inflammation, however, its amount rises sharply. A 2008 study in the journal Gastroenterology showed that KPV enters cells of the inflamed mucosa directly via PepT1. In mice with chemically induced colitis, KPV given in drinking water then reduced inflammation, weight loss and mucosal damage.[2]
KPV therefore acts preferentially where the inflammation is – in theory a big advantage over drugs that suppress immunity throughout the body.
What are KPV nanoparticles?
To get KPV to the colon intact, scientists tried “packaging” it in nanoparticles. In one study the nanoparticles were enclosed in a polysaccharide gel that only dissolves in the colon.[4] In another, the nanoparticles were coated with hyaluronic acid, which binds to the CD44 receptor on inflamed cells. In mice with ulcerative colitis, KPV delivered this way reduced inflammation at a much lower dose than the peptide alone.[5]
| Study | Model | Route of administration | Result |
|---|---|---|---|
| Dalmasso et al., 2008 | Mice with colitis | In drinking water | Less inflammation and mucosal damage[2] |
| Kannengiesser et al., 2008 | Mice, IBD models | Systemically | Anti-inflammatory effect[3] |
| Laroui et al., 2010 | Mice with colitis | Nanoparticles in a gel | Targeted action in the colon[4] |
| Xiao et al., 2017 | Mice with ulcerative colitis | Hyaluronic-acid nanoparticles | Effect at a lower dose[5] |
Does KPV also have antimicrobial effects?
Yes, at least in the laboratory. α-MSH and its short fragments, including KPV, limited the growth of the bacterium Staphylococcus aureus and the yeast Candida albicans.[6] The combination of anti-inflammatory and antimicrobial effects is of interest for research on infected wounds and skin inflammation.
What are the limitations of the research?
- No published clinical study in humans.
- Mouse colitis models are chemically induced and correspond only partly to Crohn’s disease or ulcerative colitis in humans.
- Most studies used oral or nanoparticle administration; there are few data on other routes.
- Long-term safety is unknown.
How does KPV act in the gut?
Both peptides are studied in connection with the gut, but each in a different way. KPV dampens inflammation by switching off NF-κB signals in mucosal cells.
What is the melanocortin system?
α-MSH belongs to the group of melanocortins – peptides produced by cleaving the large protein pro-opiomelanocortin (POMC). They act through five receptors, MC1R to MC5R, which control pigmentation, appetite, cortisol production, sebum and the inflammatory response. α-MSH dampens inflammation mainly via the MC1R receptor on immune cells. Other substances in this family focus on pigmentation.[1]
Why is it an advantage that KPV is so small?
The tripeptide is cheap to make, chemically stable and, thanks to the PepT1 transporter, can enter intestinal mucosa cells without having to bind to a receptor on the cell surface. Large proteins and longer peptides would be broken down in the digestive tract before reaching the inflamed mucosa. That is why KPV is of interest mainly for oral administration.[2]
Is KPV also studied for the skin?
Yes. α-MSH and its derived tripeptides have been studied in models of skin inflammation and allergic reactions, where they dampened the release of inflammatory signals from skin cells.[1] Thanks to its small size and stability, KPV is also of interest for topical use. Clinical studies in skin diseases have not been published, however.
How has KPV research developed?
The anti-inflammatory effects of α-MSH were described in the 1980s and 1990s by the group of James Lipton and Anna Catania. They gradually found that even the end of the molecule alone, the tripeptide KPV, keeps the effect. Key studies in mouse models of gut inflammation followed in 2008[2][3], and in the following decade work on nanoparticles designed to deliver KPV directly to the colon.[4][5]
Summary
- KPV is the Lys-Pro-Val tripeptide from the end of the hormone α-MSH; it dampens inflammation but does not cause pigmentation.[1]
- It enters intestinal mucosa cells via the PepT1 transporter, which is more abundant in inflamed mucosa.[2]
- In mice with colitis it reduced inflammation when given in drinking water and in nanoparticles.[2][5]
- In the laboratory it limited the growth of some bacteria and yeasts.[6]
- There are no clinical studies in humans yet.
Frequently asked questions
Is KPV the same as α-MSH?
No. KPV is just the last three amino acids of the thirteen-amino-acid α-MSH. It has kept the anti-inflammatory effect but does not act on pigmentation.
Does KPV cause tanning?
No. Melanin production is triggered by the MC1R receptor, which, according to studies, KPV does not significantly activate.
Can KPV be given orally?
In mouse studies, yes – in drinking water or in nanoparticles. This has not been verified in humans.
Are there studies of KPV in humans?
Not yet. All the data come from cell cultures and mouse models of inflammation.
Why is KPV studied specifically in the colon?
The PepT1 transporter, through which KPV enters cells, is scarce in the healthy colon, but its amount rises sharply during chronic inflammation. KPV therefore enters mainly the inflamed cells.[2]
For laboratory research we offer the KPV peptide 5 mg in stock.
Sources
- Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocrine Reviews. 2008;29(5):581–602. PubMed ↗
- Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166–178. PubMed ↗
- Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008;14(3):324–331. PubMed ↗
- Laroui H, et al. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138(3):843–853. PubMed ↗
- Xiao B, et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Molecular Therapy. 2017;25(7):1628–1640. PubMed ↗
- Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of α-MSH peptides. Journal of Leukocyte Biology. 2000;67(2):233–239. PubMed ↗
The information in this article is for educational purposes only and does not replace medical advice. The substances described are not approved medicines, and Jolt Peptides products are intended solely for laboratory research, not for use in humans or animals.