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Pharmaceuticals
Volume 18
Issue 6
10.3390/ph18060928
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Review

Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System

by
Predrag Sikiric
1,*,
Sven Seiwerth
2,
Anita Skrtic
2,
Mario Staresinic
3,
Sanja Strbe
1,
Antonia Vuksic
1,
Suncana Sikiric
2,
Dinko Bekic
1,
Dragan Soldo
1,
Boris Grizelj
1,
Luka Novosel
1,4,
Lidija Beketic Oreskovic
1,
Ivana Oreskovic
1,
Mirjana Stupnisek
1,
Alenka Boban Blagaic
1,* and
Ivan Dobric
1,3
1
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
2
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
3
Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
4
Department of Diagnostic and Interventional Radiology, University Hospital Centre, 10000 Zagreb, Croatia
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(6), 928; https://doi.org/10.3390/ph18060928
Submission received: 28 April 2025 / Revised: 25 May 2025 / Accepted: 17 June 2025 / Published: 19 June 2025
(This article belongs to the Special Issue Application of Gastrointestinal Peptides in Medicine)
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Abstract

Although approached through many concepts, the pleiotropic healing issue, specifically, maintaining/reestablishing tissue integrity, remains a central challenge in pharmacology, particularly when the process is misdirected or not properly controlled. Robert and Szabo’s concept of cytoprotection holds that innate cell (epithelial (Robert), endothelial (Szabo)) integrity and protection/maintenance/reestablishment in the stomach is translated to other organ therapy (cytoprotection → organoprotection) via the cytoprotection agent’s effect. Therefore, we defend stable gastric pentadecapeptide BPC 157 therapy’s efficacy and pleiotropic beneficial effects, along with its high safety (LD1 not achieved), against speculation of its negative impact, speculation of angiogenesis toward tumorigenesis, increased NO and eNOS, damaging free radical formation, and neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease). Contrarily, in wound healing and general healing capabilities, as reviewed, as a cytoprotective agent and native cytoprotection mediator, BPC 157 controls angiogenesis and the NO-system’s healing functions and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson’s disease and Alzheimer’s disease), and it presents prominent anti-tumor potential in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing “angiogenic privilege” (vs. angiogenesis/neovascularization/tumorigenesis), and it does not produce corneal neovascularization but rather opposes it. Per Folkman’s concept, it demonstrates an anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on the NO-level (increase vs. decrease), always combined with the counteraction of free radical formation, and, in mice and rats, BPC 157 therapy counteracts Parkinson’s disease-like and Alzheimer’s disease-like disturbances. Thus, BPC 157 therapy means targeting angiogenesis and NO’s cytotoxic and damaging actions but maintaining, promoting, or recovering their essential protective functions.
Keywords: BPC 157; angiogenesis; nitric oxide; control/modulation BPC 157; angiogenesis; nitric oxide; control/modulation

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MDPI and ACS Style

Sikiric, P.; Seiwerth, S.; Skrtic, A.; Staresinic, M.; Strbe, S.; Vuksic, A.; Sikiric, S.; Bekic, D.; Soldo, D.; Grizelj, B.; et al. Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System. Pharmaceuticals 2025, 18, 928. https://doi.org/10.3390/ph18060928

AMA Style

Sikiric P, Seiwerth S, Skrtic A, Staresinic M, Strbe S, Vuksic A, Sikiric S, Bekic D, Soldo D, Grizelj B, et al. Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System. Pharmaceuticals. 2025; 18(6):928. https://doi.org/10.3390/ph18060928

Chicago/Turabian Style

Sikiric, Predrag, Sven Seiwerth, Anita Skrtic, Mario Staresinic, Sanja Strbe, Antonia Vuksic, Suncana Sikiric, Dinko Bekic, Dragan Soldo, Boris Grizelj, and et al. 2025. "Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System" Pharmaceuticals 18, no. 6: 928. https://doi.org/10.3390/ph18060928

APA Style

Sikiric, P., Seiwerth, S., Skrtic, A., Staresinic, M., Strbe, S., Vuksic, A., Sikiric, S., Bekic, D., Soldo, D., Grizelj, B., Novosel, L., Beketic Oreskovic, L., Oreskovic, I., Stupnisek, M., Boban Blagaic, A., & Dobric, I. (2025). Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System. Pharmaceuticals, 18(6), 928. https://doi.org/10.3390/ph18060928

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