Ultimate GI Repair

1. Butler, R. J., Marchesi, S., Royer, T., & Davis, I. S. (2007). Effective Therapy of Transected Quadriceps Muscle in Rat:Gastric Pentadecapeptide BPC 157. Journal of Orthopaedic Research September, 25(June), 1121–1127. https://doi.org/10.1002/jor

2. Brcic, L., Brcic, I., Staresinic, M., Novinscak, T., Sikiric, P., & Seiwerth, S. (2009). Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing. Journal of Physiology and Pharmacology : An Official Journal of the Polish Physiological Society, 60 Suppl 7, 191–196.

3. Cerovecki, T., Bojanic, I., Brcic, L., Radic, B., Vukoja, I., Seiwerth, S., & Sikiric, P. (2010). Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Journal of Orthopaedic Research, 28(9), 1155–1161. https://doi.org/10.1002/jor.21107

4. Chang, C. H., Tsai, W. C., Hsu, Y. H., & Pang, J. H. S. (2014). Pentadecapeptide bpc 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules, 19(11), 19066–19077. https://doi.org/10.3390/molecules191119066

5. Chang, C. H., Tsai, W. C., Lin, M. S., Hsu, Y. H., & Su Pang, J. H. (2011). The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. Journal of Applied Physiology, 110(3), 774–780. https://doi.org/10.1152/japplphysiol.00945.2010

6. Gjurasin, M., Miklic, P., Zupancic, B., Perovic, D., Zarkovic, K., Brcic, L., Sikiric, P. (2010). Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regulatory Peptides, 160(1–3), 33–41. https://doi.org/10.1016/j.regpep.2009.11.005

7. Gwyer, D., Wragg, N. M., & Wilson, S. L. (2019). Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell and Tissue Research, 377(2), 153–159. https://doi.org/10.1007/s00441-019-03016-8

8. Perovic, D., Kolenc, D., Bilic, V., Somun, N., Drmic, D., Elabjer, E., … Sikiric, P. (2019). Stable
gastric pentadecapeptide BPC 157 can improve the healing course of
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9. Pevec, D., Novinscak, T., Brcic, L., Sipos, K., Jukic, I., Staresinic, M., … Sikiric, P. (2010). Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Medical Science Monitor, 16(3), 81–88. https://pubmed.ncbi.nlm.nih.gov/20190676/

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1.Gopalakrishnan, S., Tripathi, A., Tamiz, A. P., Alkan, S. S., & Pandey, N. B. (2012). Larazotide acetate promotes tight junction assembly in epithelial cells. Peptides, 35(1), 95–101. https://doi.org/10.1016/j.peptides.2012.02.016

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3.
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4. Khaleghi, S., Ju, J. M., Lamba, A., & Murray, J. A. (2016). The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate. Therapeutic advances in gastroenterology, 9(1), 37–49. https://doi.org/10.1177/1756283X15616576

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6. Serena, G., Kelly, C. P., & Fasano, A. (2019). Nondietary Therapies for Celiac Disease. Gastroenterology clinics of North America, 48(1), 145–163. https://doi.org/10.1016/j.gtc.2018.09.011

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In a mice model of colitis (colon inflammation), oral administration of KPV (added to drinking water) inhibited the activation of NF-κB and MAP kinase inflammatory signalling pathways and reduced pro-inflammatory cytokine secretion.
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166–178. doi:10.1053/j.gastro.2007.10.026

KPV exerts its anti-inflammatory activities through inhibition of NF-kappaB translocation and activation of MC(1) receptor/cAMP.
- Mandrika I, Muceniece R, Wikberg JE. Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. BiochemPharmacol. 2001;61(5):613-21.
- Haddad JJ, Lauterbach R, Saadé NE, Safieh-garabedian B, Land SC. Alpha-melanocyte-related tripeptide, Lys-d-Pro-Val, ameliorates endotoxin-induced nuclear factor kappaB translocation and activation: evidence for involvement of an interleukin-1beta193-195 receptor antagonism in the alveolar epithelium. Biochem J. 2001;355(Pt 1):29-38.

In an animal model of colitis, KPV significantly reduced intestinal inflammation.
- Rajora N, Boccoli G, Catania A, et al. α-MSH modulates experimental inflammatory bowel disease. Peptides. 1997;18:381–385.
- Oktar BK, Ercan F, Ye en BC, et al. The effect of α-melanocyte stimulating hormone on colonic inflammation in the rat. Peptides. 2000;21:1271–1277.

KPV fights inflammation by inhibiting tumuor necrosis factor-α stimulated NF-κB activity and suppressing antigen-induced lymphocyte proliferation.
- Kelly JM, Moir AJ, Carlson K, et al. Immobilized α-melanocyte stimulating hormone 10–13 (GKPV) inhibits tumor necrosis factor-α stimulated NF-κB activity. Peptide. 2006;27:431–437.
-Cooper A, Robinson SJ, Pickard C, et al. α-melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status. J Immunol. 2005;175:4806–4813.

KPV suppresses inflammation through modulation of physiological responses in host defence.
-Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB J. 1989;3(11):2282-4.

KPV exhibits its anti-inflammatory effect through inhibition of IL-1beta functions.
-Getting SJ, Schioth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J PharmacolExpTher. 2003;306(2):631-7.

KPV fights inflammation by stimulating cAMP generation in a concentration- dependent way.
-Schiöth HB, Muceniece R, Mutule I, Wikberg JE. New melanocortin 1 receptor binding motif based on the C-terminal sequence of alpha-melanocyte-stimulating hormone. Basic ClinPharmacolToxicol. 2006;99(4):287-93.

KPV combats inflammation by significantly inhibiting NF-kappaB activity.
- Kelly JM, Moir AJ, Carlson K, Yang Y, Macneil S, Haycock JW. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity. Peptides. 2006;27(2):431-7.

Several studies have shown a significant reduction of pro‐inflammatory substances such as IL1 β, IL6, TNFα, IL8, Groα, and interferon γ (IFNγ) following KPV treatment.
-Luger T A, Scholzen T, Grabbe S. The role of α‐melanocyte stimulating hormone in cutaneous biology. J Invest DermatolSympProc 1997287–93.
- Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. Alpha-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. Endocr Rev. 2008;29(5):581-602.

In murine models of colitis, KPV treatment showed significant anti-inflammatory effects which suggests that it can be an important therapeutic option in treating inflammatory bowel disease.
- Klaus Kannengiesser, MD, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease, Inflammatory Bowel Diseases, Volume 14, Issue 3, 1 March 2008, Pages 324–331, https://doi.org/10.1002/ibd.20334.

In a mice model of ulcerative colitis, oral administration of KPV loaded into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs) was effective in alleviating intestinal inflammation.
- 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.

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9. Sturniolo, G. C., Fries, W., Mazzon, E., Di Leo, V., Barollo, M., & D’inca, R. (2002). Effect of zinc supplementation on intestinal permeability in experimental colitis. The Journal of laboratory and clinical medicine, 139(5), 311–315. https://doi.org/10.1067/mlc.2002.123624

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