Pentadecapeptide BPC 157 and the central nervous system

Abstract

We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157, three very recent demonstrations that may be essential in the gut-brain and brain-gut axis operation, and therapy application in the central nervous system disorders, in particular. Firstly, given in the reperfusion, BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke, sustained brain neuronal damages were resolved in rats as well as disturbed memory, locomotion, and coordination. This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats. Secondly, there are L-NG-nitro arginine methyl ester (L-NAME)- and haloperidol-induced catalepsy as well as the rat acute and chronic models of ‘positive-like’ schizophrenia symptoms, that BPC 157 counteracted, and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine (dopamine agents application), MK-801 (non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration (to induce sensitivity). Thirdly, after rat spinal cord compression, there were advanced healing and functional recovery (counteracted tail paralysis). Likewise, in BPC 157 therapy, there is specific support for each of these topics: counteracted encephalopathies; alleviated vascular occlusion disturbances (stroke); counteracted dopamine disturbances (dopamine receptors blockade, receptors super sensitivity development, or receptor activation, over-release, nigrostriatal damage, vesicles depletion), and nitric oxide-system disturbances (“L-NAME non-responsive, L-arginine responsive,” and “L-NAME responsive, L-arginine responsive”) (schizophrenia therapy); inflammation reduction, nerve recovery in addition to alleviated hemostasis and vessels function after compression (spinal cord injury therapy). Thus, these disturbances may be all resolved within the same agent’s beneficial activity, i.e., the stable gastric pentadecapeptide BPC 157.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats

“…The stable gastric pentadecapeptide BPC 157 was chosen and tested in this study due to its beneficial effects in major vessel occlusion syndromes ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ; Gojkovic et al, 2021a ; Knezevic et al, 2021a ; Knezevic et al, 2021a ; Gojkovic et al, 2021b ; Knezevic et al, 2021b ; Strbe et al, 2021 ) and as a prototypic cytoprotective peptide (for review, see Sikiric et al, 1993a ; Sikiric et al, 2006 ; Sikiric et al, 2010 ; Sikiric et al, 2011 ; Sikiric et al, 2012 ; Sikiric et al, 2013 ; Sikiric et al, 2014 ; Sikiric et al, 2016 ; Sikiric et al, 2017 ; Sikiric et al, 2018 ; Sikiric et al, 2020a ; Sikiric et al, 2020b ; Seiwerth et al, 2014 ; Seiwerth et al, 2018 ; Seiwerth et al, 2021 ; Kang et al, 2018 ; Park et al, 2020 ; Gwyer et al, 2019 , Vukojevic et al, 2022 ).…”

“…BPC 157 acts as a membrane stabilizer and free radical scavenger and reduces leaky gut syndrome, as shown in gastrointestinal tract cytoprotective studies ( Park et al, 2020 ). BPC 157 also has a curative effect due to interactions with several molecular pathways ( Tkalcević et al, 2007 ; Chang et al, 2011 , 2014 ; Huang et al, 2015 ; Hsieh et al, 2017 ; Kang et al, 2018 ; Vukojevic et al, 2018 ; Wang et al, 2019 ; Cesarec et al, 2013; Hsieh et al, 2020 ; Park et al, 2020 ; Vukojevic et al, 2020 ; Wu et al, 2020 ).…”

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

“…Finally, it should be highlighted that the results of animal studies per se should be interpreted cautiously, particularly those from lithium studies [ 17 ] (note, the original Cade study used a 0.5% lithium solution in guinea pigs) [ 109 ]. Similarly, there is a relative paucity of clinical data on BPC 157 [ 10 , 11 , 12 , 13 , 14 ]. Nonetheless, BPC 157 has been proven to be efficacious in the treatment of ulcerative colitis, both in clinical settings [ 110 , 111 ] and in experimental rats with ulcerative colitis in ischemic/reperfusion studies [ 21 ] and other ulcerative colitis models, including various species [ 85 , 86 , 87 , 88 , 89 , 90 , 101 , 112 , 113 ] and complications (for a review see [ 114 ]).…”

“…Recently, we demonstrated that the stable gastric pentadecapeptide BPC 157 (for a review see [ 10 , 11 , 12 , 13 , 14 ]) may counteract the adverse effects of the administration of a huge dose of lithium sulfate (500 mg/kg ip) in rats [ 15 ]; dose selection in accordance to the counteracted magnesium-high dose toxicity [ 16 ] showed that many direct targets of lithium are likely magnesium-dependent intracellular enzymes [ 17 ]. Otherwise, an immediate severe syndrome was produced (severe muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas (with the most prominent being in the cerebral cortex)) [ 15 ].…”

“…Lithium has been used for over half a century to treat affective disorders. Due to lithium’s narrow therapy window [ 17 ], BPC 157 has been implicated in the functioning of the brain–gut axis and has been shown to interact, as a modulator, with several neurotransmitters (for a review, see, i.e., [ 12 , 14 ]). It may counteract not only the acute and chronic toxicities of amphetamines [ 42 , 43 , 44 ], but also neuroleptic-induced catalepsy [ 44 , 45 ], in addition to other neuroleptic adverse effects (i.e., somatosensory disorientation [ 45 ], gastric ulcers [ 45 , 46 , 47 ], sphincter dysfunction [ 41 ], and prolonged QT-interval [ 48 ]) and L-NAME- and NOS blocker-induced catalepsy [ 44 ].…”