BPC-157 Spray

BPC-157 is a synthetic peptide fragment currently under scientific investigation for its observed effects in non-human biological systems. Studies have reported its influence on tissue repair processes in various animal models, including effects on tendon, ligament, and gastrointestinal tissues.

These experimental observations contribute to ongoing efforts to characterize its biological activity and potential research applications.

BPC-157 in Wound Healing and Tissue Regeneration

BPC-157 appears to accelerate wound closure and improve healing quality in several models, including incisional, excisional, burn, diabetic, and ischemic wounds. It may promote granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition, potentially through upregulation of growth factors such as VEGF and modulation of the ERK1/2 signaling pathway.^[1]

In ischemic conditions, BPC-157 has been reported to restore blood flow and enhance healing, possibly via interactions with the nitric oxide (NO) system.^[2]

Evidence suggests BPC-157 could facilitate the healing of musculoskeletal soft tissues, including tendon, ligament, and muscle, by promoting tendon outgrowth, cell survival under stress, and cell migration, likely through activation of the FAK-paxillin pathway.^[3][4]

It may also upregulate growth hormone receptor expression in tendon fibroblasts, potentially enhancing the effects of growth hormone on cell proliferation and tissue repair.^[5]

In models of myotendinous junction injury, BPC-157 has been associated with restoration of tissue structure and function, reduction of inflammation, and prevention of muscle atrophy.^[6]

BPC-157 and Gastrointestinal Protection

BPC-157 is thought to provide strong protection to both stomach cells and the endothelium, possibly exceeding the effects of standard cytoprotective agents. This dual action may help maintain GI mucosal integrity and support healing in various organs.^[7]

The peptide appears to activate blood vessels toward sites of injury or obstruction, potentially facilitating reestablishment of blood flow and tissue repair. Its angiogenic potential and ability to promote collateral vessel formation are highlighted as important for counteracting GI lesions and vascular failure.^[8]

In animal models, BPC-157 has reportedly shown consistent protective effects against gastric and duodenal lesions induced by stress, cysteamine, and ethanol, sometimes outperforming reference drugs such as H2 receptor antagonists and dopamine promoters.^[9]

There is evidence that BPC-157 may counteract the cytotoxic effects of NSAIDs, stabilizing intestinal permeability and reducing GI, liver, and brain toxicity in preclinical studies.^[10]

BPC-157 is described as effective in healing various GI injuries, including anastomosis and fistulas, even when treatment is delayed, and may support recovery in conditions like short-bowel syndrome.^[11]

BPC-157 and Musculoskeletal Recovery

Animal studies have reported that BPC-157 may result in:

• Improved walking patterns and functional recovery after muscle-to-bone detachment^[12]
• Restoration of muscle and tendon structure, with defects disappearing and tissue organization returning to near-normal^[6]
• Enhanced early functional recovery and vascularization in tendon-to-bone healing^[13]
• Reduction of muscle contractures, edema, and muscle fiber loss following injury or pharmacological insult^[14]

BPC-157 and Vascular Effects

There is evidence suggesting that BPC-157 may act as a potent angiomodulatory agent, potentially influencing the formation of new blood vessels (angiogenesis and vasculogenesis) through various vasoactive pathways such as nitric oxide (NO), vascular endothelial growth factor (VEGF), and focal adhesion kinase (FAK).^[15]

These actions may optimize vascular responses to injury, including endothelium damage, clotting, thrombosis, vasoconstriction, vasodilation, vasculoneogenesis, and edema formation, which could contribute to improved healing processes.^[15]

There is evidence suggesting BPC-157 promotes angiogenesis both in vivo and in vitro, potentially by upregulating and activating VEGFR2 and its downstream Akt-eNOS signaling pathway, which may accelerate blood flow recovery and increase vessel density in ischemic tissues.^[16]

BPC-157 appears to induce concentration-dependent, endothelium-dependent vasodilation in isolated rat aorta, likely mediated by NO. The peptide may activate the Src-Caveolin-1-eNOS pathway, leading to increased NO production and enhanced vascular endothelial cell migration. This effect seems to be abolished by NO synthase inhibition, suggesting a strong dependence on NO signaling.^[17]

Several studies indicate that BPC-157 might rapidly activate collateral vessel pathways, allowing minor vessels to compensate for occluded major vessels and reorganize blood flow. This effect could be particularly relevant in models of major vessel occlusion, where BPC-157 therapy reportedly attenuates or eliminates portal, caval, and intracranial hypertension, aortal hypotension, and multiple organ dysfunction.^[18]

Spectroscopic analysis suggests that BPC-157 may induce rapid changes in lipid content and protein secondary structure in blood vessels, possibly protecting vascular cells from early stages of cell death.^[19]

In ocular models, BPC-157 therapy has been associated with normalization of intraocular pressure, restoration of retinal and choroidal blood vessel function, and protection against ischemic and traumatic injuries. These effects may be linked to the peptide’s broader vascular rescuing capabilities and its ability to activate collateral pathways.^[20]

BPC-157 and Inflammatory Response

Evidence suggests that BPC-157 may stimulate the expression of genes involved in tissue healing and modulate pathways related to inflammation, such as those involving proinflammatory cytokines (e.g., TNF-alpha, IL-12, IL-17, IL-23) that are central to conditions like psoriasis and inflammatory bowel disease (IBD).^[21]

Some studies suggest that BPC-157 may downregulate proinflammatory cytokines and correct deranged muscle proliferation associated with chronic inflammation and oxidative stress, such as in cancer cachexia.^[22]

There is also some evidence that BPC-157 could influence the immune response by modulating the expression of genes responsible for cytokine and growth factor generation, which are critical in the inflammatory cascade.^[21]

BPC-157 and Neural Protection

In rat models, BPC-157 administration has been associated with improved outcomes following neural injury. For example, after spinal cord injury, BPC-157 treatment reportedly led to better motor function recovery, reduced neuronal and axonal necrosis, and less demyelination and cyst formation, suggesting a possible role in counteracting secondary injury processes.^[23]

In models of brain ischemia/reperfusion injury, BPC-157 treatment was linked to preserved memory and motor function, as well as reduced pathological changes, potentially through mechanisms involving the NO-system.^[24]

There is some suggestion that BPC-157, as a gastric peptide, could influence central nervous system disorders via the brain-gut axis, with observed effects on serotonergic and dopaminergic systems and behavioral disturbances related to neurotransmitter dysregulation.^[24]

References

1. Seiwerth, S., Milavić, M., Vukojević, J., Gojkovic, S., Krezic, I., Vuletić, L., Pavlov, K., Petrovic, A., Sikirić, S., Vraneš, H., Prtorić, A., Zizek, H., Durasin, T., Dobrić, I., Starešinić, M., Štrbe, S., Knežević, M., Šola, M., Kokot, A., Sever, M., Lovrić, E., Škrtić, A., Blagaic, A., & Sikiric, P. (2021). Stable Gastric Pentadecapeptide BPC 157 and Wound Healing. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.627533.
2. Šitum, A. (2015). Učinak pentadekapeptida BPC 157 na cijeljenje rane u uvjetima inducirane ishemije stražnjih nogu štakora [Pentadecapeptide BPC 157 and wound healing after hind limb ischemia].
3. Gwyer, D., Wragg, N., & Wilson, S. (2019). Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell and Tissue Research, 377, 153 – 159. https://doi.org/10.1007/s00441-019-03016-8.
4. Chang, C., Tsai, W., Lin, M., Hsu, Y., & Pang, J. (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, 774-80 . https://doi.org/10.1152/japplphysiol.00945.2010.
5. Chang, C., Tsai, W., Hsu, Y., & Pang, J. (2014). Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts. Molecules, 19, 19066 – 19077. https://doi.org/10.3390/molecules191119066.
6. Japjec, M., Pavlov, K., Petrović, A., Starešinić, M., Šebečić, B., Buljan, M., Vraneš, H., Giljanovic, A., Drmic, D., Japjec, M., Prtorić, A., Lovrić, E., Vuletić, B., Dobrić, I., Blagaić, B., Škrtić, A., Seiwerth, S., & Predrag, S. (2021). Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats. Biomedicines, 9. https://doi.org/10.3390/biomedicines9111547.
7. Sikiric, P., Ručman, R., Turković, B., Sever, M., Klicek, R., Radić, B., Drmic, D., Stupnisek, M., Mišić, M., Vuletić, L., Pavlov, K., Barišić, I., Kokot, A., Peklić, M., Štrbe, S., Blagaic, A., Tvrdeić, A., Rokotov, D., Vrčić, H., Starešinić, M., & Seiwerth, S. (2018). Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing.. Current pharmaceutical design, 24 18, 1990-2001 . https://doi.org/10.2174/1381612824666180608101119.
8. Sikiric, P., Sever, M., Krezic, I., Vraneš, H., Kalogjera, L., Smoday, I., Vukovic, V., Oroz, K., Coric, L., Škoro, M., Kavelj, I., Zubcic, S., Sikirić, S., Orešković, B., Orešković, I., Blagaić, V., Brcic, K., Štrbe, S., Starešinić, M., Blagaić, B., Škrtić, A., & Seiwerth, S. (2024). New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection.. Inflammopharmacology. https://doi.org/10.1007/s10787-024-01499-8.
9. Sikiric, P., Seiwerth, S., Grabarević, Ž., Petek, M., Ručman, R., Turković, B., Rotkvić, I., Jagić, V., Duvnjak, M., Miše, S., Djačić, S., Šeparović, J., Veljača, M., Sallmani, A., Banic, M., & Brkić, T. (1994). The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides.. Life sciences, 54 5, PL63-8 . https://doi.org/10.1016/0024-3205(94)00796-9.
10. Park, J., Lee, H., Sikiric, P., & Hahm, K. (2020). BPC157 rescued NSAID-cytotoxicity via stabilizing intestinal permeability and enhancing cytoprotection.. Current pharmaceutical design. https://doi.org/10.2174/1381612826666200523180301.
11. Sikiric, P., Seiwerth, S., Ručman, R., Turković, B., Rokotov, D., Brčić, L., Sever, M., Klicek, R., Radić, B., Drmic, D., Ilić, S., Kolenc, D., Vrčić, H., & Šebečić, B. (2011). Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.. Current pharmaceutical design, 17 16, 1612-32 . https://doi.org/10.2174/138161211796196954.
12. Matek, D., Matek, I., Staresinic, E., Japjec, M., Bojanic, I., Blagaić, B., Orešković, B., Orešković, I., Žiger, T., Novinščak, T., Krezic, I., Štrbe, S., Drinković, M., Brkić, F., Popic, J., Škrtić, A., Seiwerth, S., Starešinić, M., Sikiric, P., & Brizić, I. (2025). Stable Gastric Pentadecapeptide BPC 157 as Therapy After Surgical Detachment of the Quadriceps Muscle from Its Attachments for Muscle-to-Bone Reattachment in Rats. Pharmaceutics, 17. https://doi.org/10.3390/pharmaceutics17010119.
13. Krivić, A., Majerović, M., Jelić, I., Seiwerth, S., & Sikiric, P. (2008). Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflammation Research, 57, 205-210. https://doi.org/10.1007/s00011-007-7056-8.
14. Stambolija, V., Stambolija, T., Holjevac, J., Murselović, T., Radonić, J., Duzel, V., Duplancic, B., Uzun, S., Živanović-Posilović, G., Kolenc, D., Drmic, D., Romić, Ž., Seiwerth, S., & Sikiric, P. (2016). BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.. European journal of pharmacology, 781, 83-91 . https://doi.org/10.1016/j.ejphar.2016.04.004.
15. Seiwerth, S., Brčić, L., Vuletić, L., Kolenc, D., Aralica, G., Mišić, M., Zenko, A., Drmic, D., Ručman, R., & Sikiric, P. (2014). BPC 157 and blood vessels.. Current pharmaceutical design, 20 7, 1121-5 . https://doi.org/10.2174/13816128113199990421.
16. Hsieh, M., Liu, H., Wang, C., Huang, H., Lin, Y., Ko, Y., Wang, J., Chang, V., & Pang, J. (2017). Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. Journal of Molecular Medicine, 95, 323-333. https://doi.org/10.1007/s00109-016-1488-y.
17. Hsieh, M., Lee, C., Chueh, H., Chang, G., Huang, H., Lin, Y., & Pang, J. (2020). Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Scientific Reports, 10. https://doi.org/10.1038/s41598-020-74022-y.
18. Štrbe, S., Smoday, I., Krezic, I., Kalogjera, L., Vukovic, V., Zizek, H., Gojkovic, S., Vraneš, H., Barišić, I., Sikirić, S., Tepeš, M., Oroz, K., Brkić, F., Drinković, M., Orešković, B., Popić, J., Blagaić, B., Škrtić, A., Starešinić, M., Seiwerth, S., & Sikiric, P. (2023). Innate Vascular Failure by Application of Neuroleptics, Amphetamine, and Domperidone Rapidly Induced Severe Occlusion/Occlusion-like Syndromes in Rats and Stable Gastric Pentadecapeptide BPC 157 as Therapy. Pharmaceuticals, 16. https://doi.org/10.3390/ph16060788.
19. Gamulin, O., Oroz, K., Coric, L., Krajačić, M., Škrabić, M., Dretar, V., Štrbe, S., Talapko, J., Juzbašić, M., Krezic, I., Lozić, M., Stambolija, V., Zizek, H., Jurca, I., Jurjević, I., Blagaic, A., Škrtić, A., Seiwerth, S., & Sikiric, P. (2022). Fourier Transform Infrared Spectroscopy Reveals Molecular Changes in Blood Vessels of Rats Treated with Pentadecapeptide BPC 157. Biomedicines, 10. https://doi.org/10.3390/biomedicines10123130.
20. Sikiric, P., Kokot, A., Kralj, T., Zlatar, M., Masnec, S., Lazić, R., Lončarić, K., Oroz, K., Sablić, M., Boljesic, M., Antunović, M., Sikirić, S., Štrbe, S., Stambolija, V., Orešković, B., Kavelj, I., Novosel, L., Zubcic, S., Krezic, I., Škrtić, A., Jurjević, I., Blagaić, B., Seiwerth, S., & Starešinić, M. (2023). Stable Gastric Pentadecapeptide BPC 157—Possible Novel Therapy of Glaucoma and Other Ocular Conditions. Pharmaceuticals, 16. https://doi.org/10.3390/ph16071052.
21. Sikiric, P., Hahm, K., Blagaic, A., Tvrdeić, A., Pavlov, K., Petrovic, A., Kokot, A., Gojkovic, S., Krezic, I., Drmic, D., Ručman,
22. Sikiric, P., Seiwerth, S., Ručman, R., Turković, B., Rokotov, D., Brčić, L., Sever, M., Klicek, R., Radić, B., Drmic, D., Ilić, S., Kolenc, D., Stambolija, V., Zoričić, Z., Vrčić, H., & Šebečić, B. (2012). Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.. Current medicinal chemistry, 19 1, 126-32 . https://doi.org/10.2174/092986712803414015.
23. , & Seiwerth, S. (2019). Stable Gastric Pentadecapeptide BPC 157, Robert’s Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye’s Stress Coping Response: Progress, Achievements, and the Future. Gut and Liver, 14, 153 – 167. https://doi.org/10.5009/gnl18490.
24. Perović, D., Kolenc, D., Bilić, V., Somun, N., Drmic, D., Elabjer, E., Buljat, G., Seiwerth, S., & Sikiric, P. (2019). Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats. Journal of Orthopaedic Surgery and Research, 14. https://doi.org/10.1186/s13018-019-1242-6.
25. Vukojević, J., Vrdoljak, B., Malekinušić, D., Siroglavić, M., Milavić, M., Kolenc, D., Blagaić, B., Batelja, L., Drmic, D., Seiverth, S., & Sikiric, P. (2020). The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats. Brain and Behavior, 10. https://doi.org/10.1002/brb3.1726.
26. Sikiric, P., Seiwerth, S., Ručman, R., Kolenc, D., Vuletić, L., Drmic, D., Grgić, T., Štrbe, S., Zukanović, G., Crvenković, D., Madžarac, G., Rukavina, I., Sučić, M., Barić, M., Starčević, N., Krstonijević, Z., Benčić, M., Filipčić, I., Rokotov, D., & Vlainić, J. (2016). Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Current Neuropharmacology, 14, 857 – 865. https://doi.org/10.2174/1570159X13666160502153022.

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