BPC 157 Therapy: Targeting Angiogenesis and Nitric Oxide's Cytotoxic and Damaging Actions, but Maintaining, Promoting, or Recovering Their Essential Protective Functions. Comment on Józwiak et al. Multifunctionality and Possible Medical Application of the BPC 157 Peptide-Literature and Patent Review. Pharmaceuticals 2025, 18, 185

Predrag Sikiric; Sven Seiwerth; Anita Skrtic; Mario Staresinic; Sanja Strbe; Antonia Vuksic; Suncana Sikiric; Dinko Bekic; Dragan Soldo; Boris Grizelj; Luka Novosel; Lidija Beketic Oreskovic; Ivana Oreskovic; Mirjana Stupnisek; Alenka Boban Blagaic; Ivan Dobric

doi:10.3390/ph18101450

BPC 157 Therapy: Targeting Angiogenesis and Nitric Oxide's Cytotoxic and Damaging Actions, but Maintaining, Promoting, or Recovering Their Essential Protective Functions. Comment on Józwiak et al. Multifunctionality and Possible Medical Application of the BPC 157 Peptide-Literature and Patent Review. Pharmaceuticals 2025, 18, 185

Pharmaceuticals (Basel). 2025 Sep 28;18(10):1450. doi: 10.3390/ph18101450.

Authors

Predrag Sikiric¹, Sven Seiwerth², Anita Skrtic², Mario Staresinic², Sanja Strbe¹, Antonia Vuksic¹, Suncana Sikiric², Dinko Bekic¹, Dragan Soldo¹, Boris Grizelj¹, Luka Novosel^{1

3}, Lidija Beketic Oreskovic¹, Ivana Oreskovic¹, Mirjana Stupnisek¹, Alenka Boban Blagaic¹, Ivan Dobric^{1

4}

Affiliations

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 Diagnostic and Interventional Radiology, University Hospital Centre, 10000 Zagreb, Croatia.
⁴ Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

Abstract

The healing issue is a central, not completely understood, problem in pharmacology, approached by many concepts. One of the most well-known is Robert's and Szabo's concept of cytoprotection, which holds innate cell (epithelial (Robert), endothelial (Szabo)) integrity, protection/maintenance/reestablishing in the stomach to be translated to other organ therapy (cytoprotection→organoprotection) via cytoprotection agent's effect. Thereby, we defend stable gastric pentadecapeptide BPC 157 therapy, efficacy, pleiotropic beneficial effects along with high safety (LD1 not achieved) against Józwiak and collaborators' review speculating its negative impact, speculation of angiogenesis toward tumorogenesis, increased NO and eNOS, toward damaging free radicals 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 healing functions, and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson's disease and Alzheimer's disease), and presents prominent anti-tumor potential, in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing "angiogenic privilege" (vs. angiogenesis/neovascularization/tumorogenesis), does not produce corneal neovascularization, but rather opposes it, and per Folkman's concept, it demonstrates anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on NO-level (increase vs. decrease), always combined with counteraction of free radicals 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; control/modulation; nitric oxide.

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