Proposed Mechanisms of Action (Evidence-based)

1) Pro-angiogenic signaling via VEGFR2 → AKT → eNOS

Endothelial and ischemia models report increased VEGFR2 expression/internalization and activation of downstream AKT–eNOS, with enhanced tube formation and improved perfusion in a rat hind-limb ischemia assay. [oai_citation:1‡PubMed](https://pubmed.ncbi.nlm.nih.gov/27847966/?utm_source=chatgpt.com)

2) Nitric-oxide–mediated, largely endothelium-dependent vasorelaxation

Aortic ring experiments showed vasodilation that was blunted by L-NAME and hemoglobin and attenuated without endothelium—consistent with NO-mediated effects. [oai_citation:2‡PubMed](https://pubmed.ncbi.nlm.nih.gov/33051481/?utm_source=chatgpt.com) [oai_citation:3‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7555539/?utm_source=chatgpt.com)

3) Cell adhesion & migration pathways (FAK–paxillin)

In tendon fibroblasts, BPC-157 increased phosphorylation of FAK and paxillin and supported migration and stress survival. These proteins transmit integrin-linked signals controlling motility and survival. [oai_citation:4‡PubMed](https://pubmed.ncbi.nlm.nih.gov/21030672/?utm_source=chatgpt.com) [oai_citation:5‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2172300/?utm_source=chatgpt.com)

4) Growth-hormone receptor (GHR) expression in tendon fibroblasts

Gene-expression and protein studies found dose- and time-dependent up-regulation of GHR. With exogenous GH, in-vitro proliferation markers increased and JAK2 was activated—suggesting a permissive/synergistic interface with GH signaling in this cell type. [oai_citation:6‡PubMed](https://pubmed.ncbi.nlm.nih.gov/25415472/?utm_source=chatgpt.com) [oai_citation:7‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6271067/?utm_source=chatgpt.com)

5) Gastroprotective/cytoprotective actions in rodent models

Multiple rat studies describe protection/healing in NSAID-induced and other gastric ulcer paradigms, consistent with mucosal cytoprotection concepts; mechanisms proposed include NO modulation and angiogenesis. [oai_citation:8‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4717094/?utm_source=chatgpt.com) [oai_citation:9‡PubMed](https://pubmed.ncbi.nlm.nih.gov/9403784/?utm_source=chatgpt.com)

Research Evidence (Preclinical-forward)

Musculoskeletal models

• Achilles tendon transection (rat): accelerated macroscopic and histologic healing; tendocyte growth stimulation in vitro. [oai_citation:10‡PubMed](https://pubmed.ncbi.nlm.nih.gov/14554208/?utm_source=chatgpt.com)
• Tendon explant/fibroblast studies: enhanced explant outgrowth, stress survival, and migration; FAK–paxillin activation. [oai_citation:11‡PubMed](https://pubmed.ncbi.nlm.nih.gov/21030672/?utm_source=chatgpt.com)
• GHR pathway in fibroblasts: BPC-157 increased GHR expression (mRNA/protein) and, with GH, increased proliferation markers; JAK2 engagement. [oai_citation:12‡PubMed](https://pubmed.ncbi.nlm.nih.gov/25415472/?utm_source=chatgpt.com)

Vascular & endothelial studies

• Endothelium/ischemia: VEGFR2 up-regulation, VEGFR2–AKT–eNOS activation, tube formation, and enhanced blood-flow recovery in limb ischemia (rat). [oai_citation:13‡PubMed](https://pubmed.ncbi.nlm.nih.gov/27847966/?utm_source=chatgpt.com)
• Vasomotor tone: NO-mediated, largely endothelium-dependent vasorelaxation in aortic rings. [oai_citation:14‡PubMed](https://pubmed.ncbi.nlm.nih.gov/33051481/?utm_source=chatgpt.com)

Gastrointestinal models

• Acute & chronic gastric ulcers (rat): protection and accelerated healing in several paradigms. [oai_citation:15‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4717094/?utm_source=chatgpt.com)

Human data snapshot

Published human evidence remains very limited. A recent pilot infusion study in two healthy adults reported no adverse effects up to 20 mg; the authors call for larger trials. No conclusions on efficacy can be drawn from such small safety-focused work. [oai_citation:16‡PubMed](https://pubmed.ncbi.nlm.nih.gov/40131143/?utm_source=chatgpt.com)

InterpretationAcross domains, most findings are preclinical. Translation to human outcomes is unproven and requires rigorously controlled clinical trials.

Regulatory & Safety Context (for awareness)

• Not FDA-approved for any indication; appears on FDA’s 503A Category 2 (ingredients presenting significant safety risks) list for traditional compounding. [oai_citation:17‡U.S. Food and Drug Administration](https://www.fda.gov/media/94155/download?utm_source=chatgpt.com)
• Anti-doping: Listed under WADA’s S0 — Non-approved Substances (athlete-prohibited). [oai_citation:18‡U.S. Anti-Doping Agency (USADA)](https://www.usada.org/spirit-of-sport/bpc-157-peptide-prohibited/?utm_source=chatgpt.com) [oai_citation:19‡World Anti Doping Agency](https://www.wada-ama.org/en/prohibited-list?utm_source=chatgpt.com)

FAQ (Research-oriented)

Does this page make medical claims? No. It summarizes laboratory and animal research trends with citations for readers to evaluate.

What’s the most frequently cited mechanism? Endothelial/angiogenic signaling involving VEGFR2→AKT→eNOS, nitric-oxide–linked vasodilation, and cell-migration pathways (FAK–paxillin) in tendon fibroblasts. [oai_citation:20‡PubMed](https://pubmed.ncbi.nlm.nih.gov/27847966/?utm_source=chatgpt.com)

Selected PubMed / PMC References

1. Hsieh MJ et al. J Mol Med 2017 — Pro-angiogenic effects; VEGFR2–AKT–eNOS activation; hind-limb ischemia model. PubMed 27847966. [oai_citation:21‡PubMed](https://pubmed.ncbi.nlm.nih.gov/27847966/?utm_source=chatgpt.com)
2. Hsieh MJ et al. 2020 — NO-mediated, endothelium-dependent vasorelaxation. PubMed 33051481 / PMC7555539. [oai_citation:22‡PubMed](https://pubmed.ncbi.nlm.nih.gov/33051481/?utm_source=chatgpt.com) [oai_citation:23‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7555539/?utm_source=chatgpt.com)
3. Staresinic M et al. J Orthop Res 2003 — Achilles tendon transection (rat). PubMed 14554208. [oai_citation:24‡PubMed](https://pubmed.ncbi.nlm.nih.gov/14554208/?utm_source=chatgpt.com)
4. Chang CH et al. J Appl Physiol 2011 — Tendon fibroblasts; FAK–paxillin activation & migration. PubMed 21030672. [oai_citation:25‡PubMed](https://pubmed.ncbi.nlm.nih.gov/21030672/?utm_source=chatgpt.com)
5. Chang CH et al. Molecules 2014 — GHR expression ↑ in tendon fibroblasts; JAK2 with GH. PubMed 25415472 / PMC6271067. [oai_citation:26‡PubMed](https://pubmed.ncbi.nlm.nih.gov/25415472/?utm_source=chatgpt.com) [oai_citation:27‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6271067/?utm_source=chatgpt.com)
6. Xue XC et al. 2004 — Protection/healing in rat gastric ulcer models. PMC4717094. [oai_citation:28‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4717094/?utm_source=chatgpt.com)
7. Lee E et al. 2025 — Pilot infusion safety in two healthy adults (no adverse effects reported). PubMed 40131143. [oai_citation:29‡PubMed](https://pubmed.ncbi.nlm.nih.gov/40131143/?utm_source=chatgpt.com)
8. Reviews summarizing pleiotropy & limited human data: PMC7096228; PMC11053547. [oai_citation:30‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7096228/?utm_source=chatgpt.com)

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