BPC-157

BPC-157 is best known for tissue repair.

Most of the published work looks at how the body rebuilds itself after damage: tendons reattaching to bone, skin closing after a burn, cut nerves regrowing, new blood vessels forming.

1. Studied for

   New blood vessel growth

   More new vessels formed, and blood flow came back faster to a rat leg whose blood supply had been cut off. Cells / chick membrane / rat 2 independent laboratories Preclinical strong Convergent results from more than one independent laboratory across more than one experimental system. Still preclinical: 'strong' here never means clinical-grade evidence in people. Open for the full finding and the paper it came from.

   In the literature

   Angiogenesis and VEGFR2 signaling

   One study investigated BPC-157 for pro-angiogenic activity across four systems: the chick chorioallantoic membrane assay, an endothelial tube-formation assay, a rat hind-limb ischemia model read by laser Doppler scanning, and cultured human vascular endothelial cells. Researchers reported increased vessel density in the membrane assay and in tube formation, accelerated recovery of blood flow in ischemic rat hind-limb muscle with histology showing more vessels and enhanced vascular VEGFR2 expression, and increased VEGFR2 mRNA and protein, but not VEGF-A, in the human endothelial cells. BPC-157 promoted VEGFR2 internalization, which was blocked in the presence of dynasore, an inhibitor of endocytosis; activation of the VEGFR2-Akt-eNOS pathway could also be suppressed by dynasore, and the increase in endothelial tube formation was likewise inhibited by dynasore. A second laboratory, independent of the first, reported convergent results in its own work: up-regulation of VEGF-a, enhanced proliferation and migration of human umbilical vein endothelial cells, and accelerated vascular tube formation in vitro.^{References 1, 2}

   Modelin vitro (cultured human vascular endothelial cells), chick chorioallantoic membrane (avian in vivo), and rodent (rat hind-limb ischemia)

   Confidence: strong

   Convergent results from more than one independent laboratory across more than one experimental system. Still preclinical: 'strong' here never means clinical-grade evidence in people.

   Source

   Hsieh MJ, Liu HT, Wang CN, Huang HY, Lin Y, Ko YS, Wang JS, Chang VH, Pang JS. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl). 2017;95(3):323-333. doi:10.1007/s00109-016-1488-y. PMID: 27847966. Convergent second laboratory: Huang T, et al. Drug Des Devel Ther. 2015;9:2485-2499. doi:10.2147/DDDT.S82030. PMID: 25995620

   PubMed 27847966 PubMed 25995620

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1007/s00109-016-1488-y returned this exact title, first author Ming-Jer Hsieh, Journal of Molecular Medicine, volume 95, issue 3, pages 323-333, epub 2016-11-15 for the 2017 Mar issue. PubMed efetch of PMID 27847966 returned the matching record and the full abstract, re-read line by line. Three verbs are taken verbatim from that abstract and are deliberately not upgraded: VEGFR2 internalization 'was blocked in the presence of dynasore'; the VEGFR2-Akt-eNOS pathway 'could also be suppressed by dynasore'; and 'The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore'. Laboratory independence was checked from the author affiliations in the two PubMed records: Chang Gung University, Taiwan for the first study, Fourth Military Medical University, Xi'an for the second. 'Strong' here means strong preclinical convergence only; no human trial underlies it.

2. Studied for

   Tendon reattaching to bone

   In rats with the Achilles cut away from the heel bone, the repair held more load before it failed and the animals walked better. Rat Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Tendon-to-bone healing after Achilles detachment

   In rats whose Achilles tendon was sharply transected from the calcaneal bone, BPC-157 was compared with saline and with 6-alpha-methylprednisolone. Researchers reported improved healing measured functionally (increased Achilles functional index), biomechanically (increased load to failure, stiffness and Young elasticity modulus), macroscopically and microscopically, and by immunohistochemistry (better organization of collagen fibers, more collagen type I, advanced vascular appearance), and reported that BPC-157 substantially reduced the healing aggravation caused by the corticosteroid. A companion study in the same rat model, focused on the first four days after transection, reported an increased Achilles functional index at all time points alongside decreased myeloperoxidase activity, decreased histological inflammatory cell influx, and an increased vascular index.^{References 3, 4}

   Modelrodent (rat Achilles tendon-to-bone transection)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res. 2006;24(5):982-989. doi:10.1002/jor.20096. PMID: 16583442. Companion: Krivic A, Majerovic M, Jelic I, Seiwerth S, Sikiric P. Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflamm Res. 2008;57(5):205-210. doi:10.1007/s00011-007-7056-8. PMID: 18594781

   PubMed 16583442 PubMed 18594781

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1002/jor.20096 returned the title, first author Andrija Krivic, Journal of Orthopaedic Research 2006, volume 24, issue 5, pages 982-989; Crossref GET /works/10.1007/s00011-007-7056-8 returned the companion, first author Krivic A., Inflammation Research 2008, volume 57, issue 5, pages 205-210. PubMed efetch of PMIDs 16583442 and 18594781 returned matching records and full abstracts, re-read this session; 'BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation' is verbatim, as are the outcome measures listed. Confidence is capped at moderate because both studies come from the same laboratory group. The animal dosing figures printed in those abstracts are deliberately not reproduced here.

3. Studied for

   Skin closing after a burn

   In burn studies on rats, wounds closed faster and new tissue formed by day 18. Rat, topical / human cells Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Skin wound healing in an alkali-burn model

   In a rat alkali-burn skin model with topical application, researchers reported accelerated wound closure and, on histology at day 18 after wounding, better granulation tissue formation, reepithelialization, dermal remodeling and a higher extent of collagen deposition than the model control group, together with increased vascular endothelial growth factor expression in the wounded skin. In parallel in vitro work with human umbilical vein endothelial cells, the same study reported enhanced proliferation, promoted migration, up-regulated VEGF-a and accelerated vascular tube formation, and reported regulation of the phosphorylation level of ERK1/2 and its downstream targets c-Fos, c-Jun and Egr-1.^{References 2}

   Modelrodent (rat alkali-burn skin wound, topical application) plus in vitro (human umbilical vein endothelial cells)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Huang T, Zhang K, Sun L, Xue X, Zhang C, Shu Z, Mu N, Gu J, Zhang W, Wang Y, Zhang Y, Zhang W. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug Des Devel Ther. 2015;9:2485-2499. doi:10.2147/DDDT.S82030. PMID: 25995620

   PubMed 25995620

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.2147/DDDT.S82030 returned this title, first author Tonglie Huang, Drug Design, Development and Therapy 2015, first page 2485. PubMed efetch of PMID 25995620 returned the matching record with the full page range 9:2485-99, PMCID PMC4425239, and the complete abstract, which was re-read to source every clause above. Author affiliation in that record is the Fourth Military Medical University, Xi'an, a laboratory independent of the Croatian and Taiwanese groups behind the rest of this page. The finding is specific to topical application in this model and says nothing about any other route.

4. Studied for

   A cut intestine knitting back together

   A cut and stitched rat intestine swelled less from day 1 and held more pressure before it leaked. Rat Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Intestinal anastomosis healing

   In rats with an ileoileal anastomosis, BPC-157 was investigated with macroscopic, histological and biomechanical assessment (volume infused, and pressure to leak induction) at intervals out to 14 days. Researchers reported that from day 1 edema was markedly attenuated and the number of granulocytes decreased, and that from days 4 or 5 necrosis decreased while granulation tissue, reticulin and collagen formation substantially increased, resulting in increased epithelization; anastomoses without leakage showed markedly higher volume and pressure values. A 2024 review from the same research program compiles anastomosis work of this type across several rat gastrointestinal models, including esophagogastric, colocolonic, jejunoileal and ileoileal anastomoses.^{References 5, 6}

   Modelrodent (rat ileoileal anastomosis), plus a narrative review of related rat anastomosis models

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Vuksic T, Zoricic I, Brcic L, Sever M, Klicek R, Radic B, Cesarec V, Berkopic L, Keller N, Blagaic AB, Kokic N, Jelic I, Geber J, Anic T, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat. Surg Today. 2007;37(9):768-777. doi:10.1007/s00595-006-3498-9. PMID: 17713731. Review: Bajramagic S, Sever M, Rasic F, et al. Stable gastric pentadecapeptide BPC 157 and intestinal anastomoses therapy in rats: a review. Pharmaceuticals (Basel). 2024;17(8):1081. doi:10.3390/ph17081081. PMID: 39204186

   PubMed 17713731 PubMed 39204186

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1007/s00595-006-3498-9 returned the title, Surgery Today 2007, volume 37, issue 9, pages 768-777, with Tihomir Vuksic as first author and Sikiric last. PubMed efetch of PMID 17713731 returned the identical record and the full abstract, from which every clause above is taken. Crossref GET /works/10.3390/ph17081081 and PubMed efetch of PMID 39204186 returned the review with first author Salem Bajramagic, Pharmaceuticals (Basel) 2024 Aug 17, 17(8):1081, and its abstract confirms the list of anastomosis models named above. The safety and route statements carried in the 2007 paper's Purpose section are deliberately not reproduced here.

5. Studied for

   Closing a channel between colon and skin

   In rats with a channel running from the colon out to the skin, both the gut wall and the skin closed over. Rat Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Colocutaneous fistula healing and dependence on the nitric-oxide system

   In a persistent rat colocutaneous fistula model, BPC-157 was given alone and together with the NOS inhibitor L-NAME, with the NO precursor L-arginine, and with their combinations, in order to test whether its effects depend on the nitric-oxide system. Researchers reported accelerated healing of the colonic and skin defects leading to closure of the fistula, assessed macroscopically, microscopically, biomechanically and functionally. On the nitric-oxide question specifically, the paper reports that L-NAME aggravated healing failure, that L-arginine was effective only when NO generation was blunted, and that all of the reported BPC-157 effects remained unchanged under L-NAME, under L-arginine, and under their co-administration.^{References 7}

   Modelrodent (rat colocutaneous fistula)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Klicek R, Sever M, Radic B, Drmic D, Kocman I, Zoricic I, Vuksic T, et al. Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system. J Pharmacol Sci. 2008;108(1):7-17. doi:10.1254/jphs.fp0072161. PMID: 18818478

   PubMed 18818478

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1254/jphs.fp0072161 returned this title, first author Robert Klicek, Journal of Pharmacological Sciences 2008, volume 108, issue 1, pages 7-17. PubMed efetch of PMID 18818478 returned the matching record and full abstract, which states verbatim: 'All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration'. L-NAME and L-arginine are described here as mechanism-probing tool compounds inside the experiment, which is why they appear in this finding and not as a suggested pairing anywhere on this page.

6. Studied for

   A cut nerve growing back

   In rats with a cut sciatic nerve, more fibers grew back and grew thicker, and the animals walked better. Rat Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Peripheral nerve regeneration

   In rats with a transected sciatic nerve, BPC-157 was investigated after application at the site of the anastomosis and, in a separate arm, directly into a tube after a 7 mm nerve segment was resected. Researchers reported faster axonal regeneration assessed histomorphometrically (improved presentation of neural fascicles, a homogeneous regeneration pattern, increased density and size of regenerative fibers, increased diameter of myelinated fibers, greater myelin sheath thickness, more myelinated fibers per area, and increased blood vessel presentation), electrophysiologically (increased motor action potentials), and functionally (improved sciatic functional index), with autotomy absent.^{References 8}

   Modelrodent (rat sciatic nerve transection)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Gjurasin M, Miklic P, Zupancic B, Perovic D, Zarkovic K, Brcic L, Kolenc D, Radic B, Seiwerth S, Sikiric P. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regul Pept. 2010;160(1-3):33-41. doi:10.1016/j.regpep.2009.11.005. PMID: 19903499

   PubMed 19903499

   How this citation was checked

   Re-resolved this session from both ends, because an earlier draft of this dossier carried a wrong DOI here. Crossref GET /works/10.1016/j.regpep.2009.11.005 returns this paper: this title, first author Miroslav Gjurasin, Regulatory Peptides 2010, volume 160, issue 1-3, pages 33-41. PubMed efetch of PMID 19903499 returned the same record with the same DOI and the full abstract, which was re-read to confirm every assessment modality listed. The discarded DOI, 10.1016/j.regpep.2009.11.014, resolves to an unrelated paper on chromogranin/secretogranin-derived antimicrobial peptides and is not cited anywhere on this page.

7. Studied for

   How blood vessels relax

   Rings of rat aorta relaxed and widened more as more BPC-157 was added, and only with the vessel lining intact. Isolated tissue Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Vasomotor tone and the Src-Caveolin-1-eNOS pathway

   Using isolated rat aorta, BPC-157 was investigated for effects on vascular tone. Researchers reported a concentration-dependent vasodilation effect that was attenuated in the absence of endothelium, which they read as an endothelium-dependent effect, although a slightly increased vasorelaxation in aorta without endothelium was noticed at high concentrations of BPC-157; there was no direct relaxation effect on a three-dimensional model made of vascular smooth muscle cells. The vasodilation was reported as nitric-oxide mediated, since adding L-NAME or hemoglobin inhibited it. BPC-157 enhanced the phosphorylation of Src, Caveolin-1 and eNOS, which the paper reports was abolished by pretreatment with a Src inhibitor, and co-immunoprecipitation showed reduced binding between Caveolin-1 and eNOS.^{References 9}

   Modelex vivo (isolated rat aortic rings) plus in vitro (vascular endothelial and smooth muscle cells)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Hsieh MJ, Lee CH, Chueh HY, Chang GJ, Huang HY, Lin Y, Pang JS. Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Sci Rep. 2020;10(1):17078. doi:10.1038/s41598-020-74022-y. PMID: 33051481

   PubMed 33051481

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1038/s41598-020-74022-y returned this title, first author Ming-Jer Hsieh, Scientific Reports 2020-10-13, volume 10, issue 1, article number 17078. PubMed efetch of PMID 33051481 returned the matching record, PMCID PMC7555539, and the full abstract. The endothelium-removal qualifier is restored verbatim from that abstract: 'Although slightly increased vasorelaxation in aorta without endothelium was noticed at high concentration of BPC 157, there was no direct relaxation effect on three-dimensional model made of vascular smooth muscle cells'. 'Abolished' is used here only where the abstract uses it: 'BPC 157 enhanced the phosphorylation of Src, Cav-1 and eNOS which was abolished by pretreatment with Src inhibitor'.

8. Studied for

   Tendon cells moving and surviving

   Rat tendon cells in a dish grew out sooner, survived a hydrogen-peroxide stress better, and moved further. Cells and explants Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

   In the literature

   Tendon fibroblast outgrowth, survival and migration in culture

   In cultured rat Achilles tendon fibroblasts and tendon explants, BPC-157 was investigated for effects on explant outgrowth, cell survival under hydrogen-peroxide oxidative stress, and cell migration and spreading. Researchers reported significantly accelerated outgrowth from explants, significantly increased cell survival under H2O2 stress, increases in migration on a transwell filter assay and in spreading, induction of F-actin formation, and increases in the phosphorylation of FAK and paxillin with total protein amounts unaltered. Cell proliferation was reported as not directly affected on the MTT assay. This study has no live-animal arm; the transected rat Achilles tendon appears only in its background as previously published work.^{References 10}

   Modelin vitro and ex vivo (cultured rat Achilles tendon fibroblasts and tendon explants)

   Confidence: preliminary

   A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

   Source

   Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011;110(3):774-780. doi:10.1152/japplphysiol.00945.2010. PMID: 21030672

   PubMed 21030672

   How this citation was checked

   Re-resolved this session. Crossref GET /works/10.1152/japplphysiol.00945.2010 returned this exact title, first author Chung-Hsun Chang, Journal of Applied Physiology, 2011, volume 110, issue 3, pages 774-780. PubMed efetch of PMID 21030672 returned the same bibliographic record plus the full abstract, re-read to confirm that the design is exclusively in vitro and ex vivo and that every effect stated above appears in the abstract. The abstract's background sentence names transected rat Achilles tendon as prior experimental work without identifying whose, so no attribution of that prior work is made here.

1 strong / 6 moderate / 1 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.