Anti-inflammatory action of a novel orally available peptide 317 in mouse models of inflammatory bowel diseases

作者：Sobczak Marta; Zakrzewski Piotr K; Cygankiewicz Adam I; Mokrowiecka Anna; Chen Chunqiu; Salaga Maciej; Malecka Panas Ewa; Kordek Radzislaw; Krajewska Wanda M; Fichna Jakub^*

来源：Pharmacological Reports, 2014, 66(5): 741-750.

DOI：10.1016/j.pharep.2014.03.007

• Abdominal pain
• Cyclic opioid peptides
• Endogenous opioid system
• Inflammatory bowel diseases
• Morphiceptin

Background: The endogenous opioid system constitutes an attractive target in the treatment of GI disorders, including inflammatory bowel diseases (IBD). The aim of our study was to characterize the anti-inflammatory and antinociceptive effect of P-317, a novel cyclic analog of opioid peptide morphiceptin, in animal models of IBD.
Methods: The anti-inflammatory effect of P-317 after intraperitoneal (ip) and oral (po) administration was assessed in two mouse models of IBD - Crohn's disease, induced by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS) and ulcerative colitis, induced by addition of dextran sodium sulfate (DSS) into drinking water. The antinociceptive action of P-317 was characterized in mice with acute colitis using mustard oil-induced pain test. Real time RT PCR was used to assess semiquantitatively the expression of IL-1 beta and TNF-alpha mRNA in mouse colonic samples. To translate our results to clinical conditions, MOP and KOP mRNA were quantified in human colonic biopsies from IBD patients.
Results: P-317 (0.1 mg/kg, ip and 1 mg/kg, po) alleviated colonic inflammation in TNBS- and DSS-treated mice in the opioid receptor-dependent manner. The anti-inflammatory effect of P-317 was associated with the decrease in mRNA expression of proinflammatory cytokines. The antinociceptive effect of P-317 was observed after ip and po administration in mice with acute colitis.
Conclusion: Our results show a potent anti-inflammatory and antinociceptive effect of P-317 in mouse models of colitis upon activation of opioid receptors. The unique bioavailability of P-317 after oral administration suggests that it is a promising drug candidate for future treatment of IBD.

• 出版日期2014-10
• 单位同济大学