The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

Abstract

Background and purpose We focused on the, yet undescribed, therapy effect of the stable gastric pentadecapeptide BPC 157 in hippocampal ischemia/reperfusion injuries, after bilateral clamping of the common carotid arteries in rats. The background is the proven therapy effect of BPC 157 in ischemia/reperfusion injuries in different tissues. Furthermore, there is the subsequent oxidative stress counteraction, particularly when given during reperfusion. The recovering effect it has on occluded vessels, results with activation of the alternative pathways, bypassing the occlusion in deep vein thrombosis. Finally, the BPC 157 therapy benefits with its proposed role as a novel mediator of Roberts’ cytoprotection and bidirectional effects in the gut‐brain axis. Materials and Methods Male Wistar rats underwent bilateral clamping of the common carotid arteries for a 20‐min period. At 30 s thereafter, we applied medication (BPC 157 10 µg/kg; or saline) as a 1 ml bath directly to the operated area, that is, trigonum caroticum. We documented, in reperfusion, the resolution of the neuronal damages sustained in the brain, resolution of the damages reflected in memory, locomotion, and coordination disturbances, with the presentation of the particular genes expression in hippocampal tissues. Results In the operated rats, at 24 and 72 hr of the reperfusion, the therapy counteracted both early and delayed neural hippocampal damage, achieving full functional recovery (Morris water maze test, inclined beam‐walking test, lateral push test). mRNA expression studies at 1 and 24 hr, provided strongly elevated ( Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, and Nos1 ) and decreased ( Nos2, Nfkb ) gene expression ( Mapk1 not activated), as a way how BPC 157 may act. Conclusion Together, these findings suggest that these beneficial BPC 157 effects may provide a novel therapeutic solution for stroke.

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing

“…Therefore, stable gastric pentadecapeptide BPC 157 is effective in wound healing (Seiwerth et al, 1997;Mikus et al, 2001;Sikiric et al, 2003;Xue et al, 2004a;Bilic et al, 2005;Seveljevic-Jaran et al, 2006;Tkalcevic et al, 2007;Huang et al, 2015), much like it is effective also in counteracting bleeding disorders (Stupnisek et al, 2012;Stupnisek et al, 2015;Vukojevic et al, 2018), produced by amputation, and/or anti-coagulants application, or major vessel occlusion, along with the evidence that pentadecapeptide BPC 157 may prevent and/or attenuate or eliminate, thus, counteracting both arterial thrombosis (Hrelec et al, 2009;Gojkovic et al, 2020;Kolovrat et al, 2020) and venous thrombosis (Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020). Consequently, the therapy signifies the recovering effect BPC 157 has on occluded vessels (Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020;Vukojevic et al, 2020), bypassing the occlusion (Duzel et al, 2017;Amic et al, 2018;Drmic et al, 2018;Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020;Vukojevic et al, 2020), appears as the specific effect of BPC 157 in ischemia/reperfusion (Duzel et al, 2017;Amic et al, 2018;Drmic et al, 2018;Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020;…”

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

“…Besides, BPC 157 therapy effect always exhibited the functional recovery as well. This was noted with peripheral nerve injury ( Gjurasin et al, 2010 ) and central nervous disturbances (i.e., traumatic brain injury ( Tudor et al, 2010 ), various encephalopathies ( Ilic et al, 2009 ; Ilic et al, 2010 ; Ilic et al, 2011a ; Ilic et al, 2011b ; Klicek et al, 2013 ; Lojo et al, 2016 ; Drmic et al, 2017 ; Medvidovic-Grubisic et al, 2017 ), stroke ( Vukojevic et al, 2020 ), and spinal cord injury ( Perovic et al, 2019 )). Likewise, there are many functional and structural similarities between the retina and brain ( Osborne et al, 2004 ), and BPC 157 can likely cross the blood–brain barrier to induce neurotransmitter release ( Tohyama et al, 2004 ; Sikiric et al, 2016 ).…”

“…This particular point supports the recent evidence that vasomotor tone is carried out through BPC 157–specific activation of the Src-Caveolin-1-endothelial NOS (eNOS) pathway ( Hsieh et al, 1997 ). Likewise, BPC 157 has a modulatory role ( Sikiric et al, 2014 ) (in particular, to the blood pressure ( Sikiric et al, 1997 ) and thrombocytes function maintenance ( Stupnisek et al, 2012 , 2015 ; Konosic et al, 2019 )) and additional interaction with several molecular pathways ( Tkalcevic et al, 2007 ; Chang et al, 2011 , 2014 ; Hsieh et al, 2017 ; 2020; Kang et al, 2018 ; Vukojevic et al, 2018 ; Vukojevic et al, 2020 ; Park et al, 2020 ; Wu et al, 2020 ) [i.e., activation of the VEGFR2-Akt-eNOS signaling pathway without the need of other known ligands or shear stress ( Hsieh et al, 2017 )]. To illustrate its modulatory role on NO-system functions ( Sikiric et al, 2014 ), BPC 157 may counteract L-NAME hypertension and pro-thrombotic effect as well as L-arginine hypotension and antithrombotic effect ( Sikiric et al, 1997 ; Stupnisek et al, 2015 ), and induce its own NO-release ( Sikiric et al, 1997 ; Turkovic et al, 2004 ).…”

“…These responses effectively negate the harmful effect of L-NAME–NOS blockade ( Duzel et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Cesar et al, 2020 ). Furthermore, there is evidence that BPC 157 counteracted stroke, given in reperfusion, after clamping of the common carotid arteries (i.e., both early and delayed neural hippocampal damage, and achieving full functional recovery (the Morris water maze test, the inclined beam-walking test, and the lateral push test)) ( Vukojevic et al, 2020 ). Likewise, BPC 157 may ameliorate other peripheral and central neuronal damage ( Ilic et al, 2009 ; Ilic et al, 2010 ; Ilic et al, 2011a ; Ilic et al, 2011b ; Gjurasin et al, 2010 ; Tudor et al, 2010 ; Klicek et al, 2013 ; Sikiric et al, 2013 ; Sikiric et al, 2016 ; Lojo et al, 2016 ; Drmic et al, 2017 ; Medvidovic-Grubisic et al, 2017 ; Perovic et al, 2019 ; Wang et al, 2019 ).…”

<p>Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157</p>

“…Numerous papers have reported that stable gastric pentadecapeptide BPC 157 can regulate angiogenesis during the healing process by rescuing the duodenal lesions in rats through interacting with the nitric oxide (NO) system and reducing of free radical formation, 14 and also can resolve pringle maneuver 15 and hippocampal ischemic damage in rats due to ischemia or reperfusion. 16 Its strong angiogenic effect is mainly via activation of the VEGF-AKT-eNOS signaling pathway. 17 Furthermore, BPC 157 has also been demonstrated to promote vascular endothelial and tendon cell proliferation and migration.…”