Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system

J Pharmacol Sci. 2008 Sep;108(1):7-17. doi: 10.1254/jphs.fp0072161.


We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.

MeSH terms

  • Anesthesia
  • Animals
  • Anti-Ulcer Agents / therapeutic use*
  • Arginine / pharmacology
  • Colonic Diseases / drug therapy*
  • Cutaneous Fistula / drug therapy*
  • Enzyme Inhibitors / pharmacology
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Peptide Fragments / therapeutic use*
  • Proteins / therapeutic use*
  • Rats
  • Rats, Wistar


  • Anti-Ulcer Agents
  • Enzyme Inhibitors
  • Peptide Fragments
  • Proteins
  • Nitric Oxide
  • BPC 157
  • Arginine
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester