Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

Abstract

There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.

Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot

“…We demonstrated that BPC 157 medication [1][2][3][4][5][6][7][8][9][10][11][12][13], given immediately after antithrombotic agents in rats, aspirin, clopidogrel, and cilostazol, counteracted their inhibitory effects on the aggregation activated by the arachidonic acid, ADP, collagen, and arachidonic acid/PGE1 used as aggregation agonists [15][16][17]20]. Contrarily, BPC 157 does not affect Thus, this suggests a particular pleiotropic effect, likely a direct effect, on thrombocyte function.…”

“…Pentadecapeptide Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, M.W. 1419, named BPC 157, a part of the sequence of human gastric juice protein, coded BPC, freely soluble in water at pH 7.0 and in saline, was prepared (Diagen, Slovenia) as described previously [1][2][3][4][5][6][7][8][9][10][11][12][13]. L-NAME and L-arginine were commercially purchased (Sigma, USA).…”

“…We focused on the inhibitory effect of the stable gastric pentadecapeptide BPC 157 (used in trials: ulcerative colitis; now, multiple sclerosis) [1][2][3][4][5][6][7][8][9][10][11][12][13] on the antithrombotic agents (i.e., aspirin, inhibitor of thromboxane A2 (TXA2) production; clopidogrel, P2Y 12 subtype of adenosine-diphosphate (ADP) receptor antagonist; and cilostazol, phosphodiesterase type 3 (PDE 3 ) inhibitor [14]). The effect on platelet aggregation and viscoelastic properties of the blood clot was investigated using multiple electrode aggregometry and modified rotational thromboelastometry (ROTEM) studies [15][16][17][18][19][20].…”

“…Recently, BPC 157 therapy (for review, see [1][2][3][4][5][6][7][8][9][10][11][12][13]) approaches solving of the vascular occlusion disturbances [21][22][23][24][25]. The rapid activation of the bypassing loop occurs in the rats with infrarenal occlusion of the inferior caval vein (and thereby resolved Virchow, venous lesion and thrombosis, caval hypertension, aortal hypotension, and consequent thrombocytopenia), much like in the rats with ischemic/reperfusion colitis, duodenal venous congestion lesions, perforated cecum, bile duct ligation-induced liver cirrhosis, and portal hypertension [21][22][23][24][25].…”

“…The rapid activation of the bypassing loop occurs in the rats with infrarenal occlusion of the inferior caval vein (and thereby resolved Virchow, venous lesion and thrombosis, caval hypertension, aortal hypotension, and consequent thrombocytopenia), much like in the rats with ischemic/reperfusion colitis, duodenal venous congestion lesions, perforated cecum, bile duct ligation-induced liver cirrhosis, and portal hypertension [21][22][23][24][25]. Previously, BPC 157, as a prototype antiulcer agent with potent cytoprotective capability [1][2][3][4][5][6][7][8][9][10][11][12][13], thereby exerting innate endothelium protection, counteracted abdominal anastomosis-induced thrombosis [26] and prolonged bleeding and thrombocytopenia after amputation and/or anticoagulant (heparin, warfarin), aspirin, and NO-agents (L-NAME/L-arginine) [27,28] and largely interacts with NO-system in various models and species [1][2][3][4][5][6][7][8][9][10][11][12][13]. While having no effect on noninjured rats or on coagulation parameters, BPC 157 in heparin-treated rats decreased prolonged activated partial thromboplastin time (APTT) but did not influence heparin activity (anti-Xa test) [27].…”