Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?

Abstract

Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress. In clinical trials without side effects, LD1 not achieved, BPC 157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis)). Further, we combine such gut-brain axis and the NO-system where BPC 157 counteracts complications of either L-NAME application (i.e., various lesions aggravation, hypertension) or Larginine application (i.e., hypotension, prolonged bleeding, thrombocytopenia). Also, BPC 157 particularly affects genes functions (i.e., Fos, c-Jun, Egr-1), all together suggestive for an indicative generalization. Thus, we could suggest gastric pentadecapeptide BPC 157 and BPC 157 induced-organoprotection as integrative mediator that integrates the adaptive bodily response to stress, and thereby practically applied in further therapy and in effective realization of Selye's stress response.

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

“…Finally, the conclusive prospect (i.e., BPC 157 application as an innate treatment to successfully oppose invasion with N. ceranae ) is supported by a variety of beneficial effects of BPC 157 noted in colitis lesion studies (Klicek et al., ; Lojo et al., ; Sikiric et al., ; Veljaca et al., ). As indicated previously, BPC 157 has been tested in clinical trials as an agent against ulcerative colitis, but studies have shown its efficacy throughout complete gastrointestinal tract (Sikiric et al., ). BPC 157 reduces high myeloperoxidase (MPO) activity in colonic tissue (Veljaca et al., ), and in particular, heals fistulas (Baric et al., ; Grgic et al., ; Klicek et al., ), rescues failed anastomosis healing (Klicek et al., ; Sever et al., ; Vuksic et al., ), and markedly improves intestinal adaptation following massive bowel resection (Sever et al., ).…”

“…The efficacy of BPC157 (Sikiric et al., , , , ; Sikiric et al., ) in reducing N. ceranae spores number in the honeybee midgut over a short period of time and suggestion that it may limit the mortality rate in honeybees and be beneficial in nosemosis type C treatment should be validated respecting particular detrimental conditions in 2014 active honeybee season (Table ), particularly favoring invasion with N. ceranae . There were more days with rain, very low average year air temperatures, alongside with mild winter, very early honeybee brood development, increasing of V. destructor mite population (Zorat, ), decreasing the immunological status of the colonies and stress caused by hunger (lack of natural food in environment).…”

“…1419, named BPC 157 which is a part of the sequence of human gastric juice protein, coded BPC, which is freely soluble in water at pH 7.0 and in saline, was prepared (Diagen, Slovenia). The peptide with 99% high pressure liquid chromatography (HPLC) purity with 1‐des‐Gly peptide as a biologically inactive impurity was used (Sikiric et al., , , , ).…”

“…Treated sugar syrup, as well as the pure sugar syrup, was administered to honeybee colony in feeders situated under the roof of the hives, for 21 consecutive days. The dose was modified according to the doses used in mammals (Sikiric et al., , ).…”

“…On the other hand, BPC 157 is an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis that largely interacts with NO‐system and is thought to be novel mediator of Robert's cytoprotection in rat studies (Sikiric et al., , , ). Thereby, BPC 157 exerts endothelium and mucosal protection in stomach, counteracts variously induced gastrointestinal lesions in different species (Duzel et al., ; Sikiric et al., , , , ), but has not been tested in social insects. Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al., ; Chang, Tsai, Hsu, & Pang, ; Chang, Tsai, Lin, Hsu, & Pang, ; Hsieh et al., ; Huang et al., ; Tkalcevic et al., ).…”