Anti-inflammatory effect of dual nociceptin and opioid receptor agonist, BU08070, in experimental colitis in mice

作者：Zielinska Marta; Ben Haddou Tanila; Cami Kobeci Gerta; Salaga Maciej; Jarmuz Agata; Padysz Milena; Kordek Radzislaw; Spetea Mariana; Hu**ands Stephen M; Fichna Jakub^*

来源：European Journal of Pharmacology, 2015, 765: 582-590.

DOI：10.1016/j.ejphar.2015.09.021

• Crohn's disease
• Inflammatory bowel diseases
• Mixed opioid agonists
• Visceral pain

Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and mu-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU08070, induces anti-inflammatory response in experimental colitis.
The anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was characterized in the mouse model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, based on the assessment of the macroscopic and microscopic total damage scores and determination of myeloperoxidase (MPO) activity and TNF-alpha level in the colon. The effect of BU08070 on cell viability and NF-kappa B was characterized in THP-1 Blue cell line. The antinociceptive activity of BU08070 was examined in mustard oil-induced mouse model of abdominal pain.
A potent anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was observed as indicated by decrease in macroscopic damage score (1.88 +/- 0.39 vs. 5.19 +/- 0.43 units in TNBS alone treated mice), MPO activity (2.29 +/- 0.37 vs. 9.64 +/- 2.55 units) and TNF-alpha level in the colon (35.85 +/- 2.45 vs. 49.79 +/- 3.81 pg/ml). The anti-inflammatory effect of BU08070 was reversed by selective NOP and MOP receptor antagonists. BU08070 produced concentration-dependent inhibition of TNF-alpha and LPS-induced NF-kappa B activation. BU08070 exerted antinociceptive action in mice with experimental colitis.
In conclusion, BU08070 significantly reduced the severity of colitis in TNBS-treated mice compared with controls. These results suggest that BU08070 is a potential therapeutic agent for inflammatory bowel diseases therapy.

• 出版日期2015-10-15