Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat

Abstract

We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection. We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier. Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene. After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 mg or 10 ng/kg) or locally as a thin layer (1.0 mg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice. Likewise, BPC 157 was effective given per-orally (0.16 mg/ml in the drinking water (12 ml/day/rat)) until sacrifice. Commonly, BPC 157 mg-ng-rats exhibited consistent functional, biomechanical, macroscopic and histological healing improvements. Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy. ß

Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract

“…In principle, BPC 157 endothelium protection/angiogenesis in ulcer healing [2,[54][55][56] follows Szabo's and Trier's demonstration of endothelium protection and angiogenesis in alcohol-stomach lesions [75]. However, whilst the Szabo's sponge-implantation with injected agents provides a suited environmental where their angiogenic potential could be tested [76], the BPC 157 angiogenesis was additionally tested in tissues that would be less healed, i.e., deep skin burns [27,28], transected major muscle [67], and particularly, in those tissues such as tendon or ligament [77][78][79] commonly thought to be hypovascular, hypocellular and hyponeural tissue where angiogenic potential (shift toward the left in presentation of new blood vessels) can be convincingly combined with the increased healing and rescuing of function [56] (of note, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress and the in vitro migration of tendon fibroblasts by the activation of the FAKpaxillin pathway [80]). What's more, the BPC 157 effect on blood vessels integrity was directly assessed and shown particularly in serosa of fully distended rat stomach: The vessels showed to become thin with distention and thereby disappeared, particularly with intragastrical alcohol, unless BPC 157 had been given [4].…”

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: Diclofenac-induced gastrointestinal, liver, and encephalopathy lesions

“…BPC 157 has been shown to counteract the liver changes induced by chronic ethanol administration (Prkacin et al 2001b), portal hypertension (Prkacin et al 2001b) and gastric lesions (Ilic et al 2009;Prkacin et al 2001a). BC157 also has been shown to reduce damage to the duodenum and colon induced by cysteamine administration (Sikiric et al 2010(Sikiric et al , 2001, and it has been demonstrated to have a prominent angiogenic effect during the healing of different types of tissues (Sikiric et al 2010(Sikiric et al , 2003(Sikiric et al , 2003Klicek et al 2008;Skorjanec et al 2009;Sever et al 2009;Tkalcevic et al 2007;Krivic et al 2006;Novinscak et al 2008;Cerovecki et al 2010). In addition, besides stimulating the expression of the egr-1 gene, BPC 157 has been shown to stimulate the expression of the egr-1 repressor nerve growth factor 1-A binding protein-2 (nab2) (Tkalcevic et al 2007).…”

Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats

“…Thus, the observed increase in urethral vessel density, which parallels LPP recovery after TU or VD in BPC 157 treated animals, specifically implies this peptide’s previously documented angiogenic effect [30] to be potentially accountable for rapid restoration of urethral function. Noticeably, it is along with a new vascular shift toward the left as shown in different models, particularly in muscle healing [13,14], even in corticosteroid-aggravated conditions [16], and also in hypovascular tissues (e.g., tendon) [30,39]. This demonstrates the prominent up-regulation of vascular endothelial growth factor (VEGF), likely with particular effect on connective tissue healing, such as the expression of early growth response 1 (EGR-1) gene and its repressor, nerve growth factor 1-A binding protein-2 (NAB2), resulting in early extracellular matrix (collagen) formation [40].…”

“…In other words, even if this study is about prevention rather than reversal of SUI, this does not diminish the relevant value of the obtained beneficial effects of BPC 157 application in rats that underwent TU and VD, since from the results it is obvious that BPC 157 therapy benefit has a long-term and sustained effect, providing the recovered LPP in TU- and VD-treated rats when the last administration had been at 24 hr before assessment (intraperitoneal regimen). BPC 157 could be easily administered (e.g., also per-orally; in drinking water) [15,17,39]. Furthermore, considering the cardiovascular effects that may be a common problem with standard SUI therapy [1,6], in vivo models of cardiovascular function showed that BPC 157 does not affect normal blood pressure or heart rhythm [42–44], but it did reduce L-NAME hypertension [44], counteract NO system failure by NOS-blockade in different models [43–45] (NO-synthesis is directly related to muscle injury healing [46]), doxorubicine chronic heart failure [42] and digitalis overdose arrhythmias [43], and in toxicology studies a lethal dose could be not achieved and no adverse effects were noted in clinical trials [7,8].…”