KPV

KPV is a tripeptide derived from α-melanocyte-stimulating hormone (α-MSH) that has been the subject of scientific investigation due to its potential anti-inflammatory and immunomodulatory properties. Research in mammalian models has provided insights into its mechanisms of action and potential therapeutic applications.

• Cytokine Modulation: Studies have shown that KPV can inhibit the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) in mammalian cells.

• Immune Cell Regulation: KPV has been observed to modulate the activity of immune cells, particularly macrophages and T cells. Research indicates that it may inhibit macrophage activation and reduce their production of reactive oxygen species (ROS) and nitric oxide (NO).

• T Cell Differentiation: Investigations have suggested that KPV may influence T cell differentiation, potentially promoting the generation of regulatory T cells (Tregs) while suppressing the development of pro-inflammatory T cell subsets.

• Melanocortin Receptor Activation: Studies have shown that KPV can activate the melanocortin receptor 1 (MC1R), which is expressed on various mammalian cell types. This activation may trigger intracellular signaling cascades that lead to the suppression of inflammatory pathways.

1. Inflammatory Bowel Disease: Research in animal models of colitis has demonstrated that KPV may reduce intestinal inflammation and improve symptoms.

2. Arthritis: Studies using mammalian models of rheumatoid arthritis and osteoarthritis have shown potential anti-arthritic effects of KPV, including reduced joint inflammation and cartilage degradation.

3. Skin Inflammation: Investigations have explored the potential of KPV in treating inflammatory skin conditions in mammalian models, with results suggesting a reduction in skin inflammation and improved barrier function.

4. Neuroprotection: Some studies in mammalian models have indicated potential neuroprotective properties of KPV, suggesting it may help reduce neuroinflammation and oxidative stress in the brain.

5. Wound Healing: Research has shown that KPV may promote wound healing in mammalian models by reducing inflammation and stimulating the proliferation and migration of skin cells.

While preclinical studies in mammalian models have not reported significant adverse effects, it is important to note that comprehensive safety data in mammals, particularly in long-term use scenarios, is still limited. Further research is needed to fully establish the safety profile of KPV.

KPV is a promising tripeptide derived from α-MSH that has demonstrated potent anti-inflammatory and immunomodulatory properties. It works by inhibiting the production of pro-inflammatory cytokines, modulating the activity of immune cells, and activating the MC1R receptor. KPV has shown potential therapeutic benefits in various inflammatory conditions, such as inflammatory bowel disease, arthritis, skin inflammation, and neurodegenerative disorders. While no significant side effects have been reported in preclinical studies, further research is needed to assess its safety and efficacy in mammals. KPV represents a novel and exciting approach to the treatment of chronic inflammatory disorders, and its development as a therapeutic agent may lead to improved outcomes for patients suffering from these debilitating conditions.

1. Zhao Y, Xue P, Lin G, Tong M, Yang J, Zhang Y, Ran K, Zhuge D, Yao Q, Xu H. A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon. Acta Biomater. 2022 Apr 15;143:233-252. doi: 10.1016/j.actbio.2022.02.039. Epub 2022 Mar 1. PMID: 35245681.

2. Shao W, Chen R, Lin G, Ran K, Zhang Y, Yang J, Pan H, Shangguan J, Zhao Y, Xu H.

3. Xiao B, Xu Z, Viennois E, Zhang Y, Zhang Z, Zhang M, Han MK, Kang Y, Merlin D. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017 Jul 5;25(7):1628-1640. doi: 10.1016/j.ymthe.2016.11.020. Epub 2017 Jan 28. PMID: 28143741; PMCID: PMC5498804.

4. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008 Jan;134(1):166-78. doi: 10.1053/j.gastro.2007.10.026. Epub 2007 Oct 17. PMID: 18061177; PMCID: PMC2431115.

5. Kannengiesser K, Maaser C, Heidemann J, Luegering A, Ross M, Brzoska T, Bohm M, Luger TA, Domschke W, Kucharzik T. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008 Mar;14(3):324-31. doi: 10.1002/ibd.20334. PMID: 18092346.

6. Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB J. 1989 Sep;3(11):2282-4. PMID: 2550304.

7. Pawar K, Kolli CS, Rangari VK, Babu RJ. Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin. J Pharm Sci. 2017 Jul;106(7):1814-1820. doi: 10.1016/j.xphs.2017.03.017. Epub 2017 Mar 24. PMID: 28343991.

8. Colombo G, Gatti S, Sordi A, Turcatti F, Carlin A, Rossi C, Lonati C, Catania A. Production and effects of alpha-melanocyte-stimulating hormone during acute lung injury. Shock. 2007 Mar;27(3):326-33. doi: 10.1097/01.shk.0000239764.80033.7e. PMID: 17304115.

9. Ichiyama T, Sato S, Okada K, Catania A, Lipton JM. The neuroimmunomodulatory peptide alpha-MSH. Ann N Y Acad Sci. 2000;917:221-6. doi: 10.1111/j.1749-6632.2000.tb05386.x. PMID: 11268347.