Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

Abstract

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva, Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The cytoprotective/adaptive cytoprotection researches largely neglect that stomach distension could per se jeopardize the mucosal integrity, with constantly stretched mucosa and blood vessels, and sphincters more prone for reflux induction. After absolute alcohol instillation in fully distended rat stomach, gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left gastric artery blood vessels clearly disappear at the serosal site, indicative for loss of vessels both integrity and function. Contrary, constant vessels presentation could predict the beneficial effect of applied agent. After pentadecapeptide BPC 157 instillation into the stomach the vessels presentation remains constant, and lesions of stomach, esophagus, and duodenum are inhibited. Standards (atropine, ranitidine, omeprazole) could only slightly improve the vessels presentation compared to control values, and they have only a partial effect on the lesions. In this review we emphasize BPC 157 unusual stability, and some of its important effects: effectiveness against various lesions in gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system, endothelium protection, effect on endothelin, and on angiogenesis promotion. It also antagonizes other alcohol effects, including acute and chronic intoxication. Given peripherally, it counteracts the consequence of central dopamine system disturbances (receptor blockade), and induces serotonin release in substantia nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in its capability to heal various wounds. Given directly into the stomach, BPC 157 instantly recovers disturbed lower esophageal and pyloric sphincter pressure in rats after 12-20 months of untreated esophagitis. All these could be suggestive for its role as a natural protectant in gastric juice with particular function throughout stomach distension.

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

“…Under the most severe conditions of transected ligament, with BPC 157 mg-ng-regimens given alone intraperitoneally, per-orally and topically, dose-regimens and application methods that had been successfully used before [1][2][3][4][5][6][7][8][9][10][11][12] and in time, the healing process on an acute ligament injury may convert rapidly from a failure to a success and all healing improvements. Function in either condition, normal (walking rats) and stressed (running rats), biomechanic, macro/microscopy were noted superior as before [1][2][3][4][5][6][7][8][9][10][11][12] in tendon studies 1,2,10 and other wound studies, 4,9,10,12 , not species related.…”

“…Function in either condition, normal (walking rats) and stressed (running rats), biomechanic, macro/microscopy were noted superior as before [1][2][3][4][5][6][7][8][9][10][11][12] in tendon studies 1,2,10 and other wound studies, 4,9,10,12 , not species related. This may be a wound healing (not found with standard peptide factors 3,16,17 ) more apt to predispose the ligament to improved healing course after transection.…”

“…1419), a partial sequence of human gastric juice protein BPC, peptide with 99% (HPLC) purity, freely soluble in water at pH 7.0 and in saline, dose ranges and ways of application as previously 1,2,[4][5][6][7][8][9][10][11]13 dissolved in saline, as follows: (i) BPC 157 10 mg or 10 ng/kg or saline 5.0 ml/kg (controls), intraperitoneally, or (ii) BPC 157 in neutral cream (1.0 mg dissolved in distilled water/g commercial neutral cream) or commercial neutral cream (controls), as a thin layer, locally, at the site of injury, administered once daily with the first application 30 min after surgery and the final application 24 h before sacrifice; (iii) BPC 157 0.16 mg/ml or nothing (controls) in the drinking water (12 ml/day/rat) until sacrifice.…”

“…We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier, using stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV) (for review, see Refs. [1][2][3][4][5][6][7][8][9][10][11][12] ). Previously, as an anti-ulcer peptide stable in human gastric juice [4][5][6][7][8][9] BPC 157 was effective in inflammatory bowel disease therapy (PL 14736) (no toxicology reported (for review, see Ref.…”

“…Also, BPC 157 particularly improved healing of transected tendon and muscle 1,2,10,11 and wound healing effect including the expression of the early growth response 1 (egr-1) gene (but also its repressor nerve growth factor 1-A binding protein-2 (nab2)). [4][5][6]9,10,12,13 Therefore, such peptide's capabilities [1][2][3][4][5][6][7][8][9][10][11][12] and responsibility for cytokine and growth factor generation and early extracellular matrix (collagen) formation may provide a peptide therapy effective functionally, biomechanically, macroscopically, and microscopically, [1][2][3][4][5][6]9,10,12,13 and thereby, suitable to improve ligament healing.…”