Abstract

Most therapies used in patients affected by inflammatory bowel diseases are ineffective in preventing the development of chronic visceral hypersensitivity, mainly due to inflammation-induced enteric neuroplasticity. Glucosinolates, secondary metabolites mainly of Brassicaceae with anti-inflammatory and neuroprotective properties, are effective in treating both neuropathic and arthritis pain through H2S release and Kv7 potassium channel activation. The aim of this work was to investigate the protective and anti-hyperalgesic efficacy of a defatted seed meal from Eruca sativa Mill. (Brassicaceae), rich in glucosinolates, in a rat model of colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS). The mechanisms of action were also investigated. Visceral pain was assessed by measuring the abdominal response to colorectal distension. Fifteen days after colitis induction, the acute administration of E. sativa defatted seed meal (0.1–1 g kg−1 p.o.) dose-dependently relieved pain. This effect was hampered by co-administering an H2S scavenger or a selective Kv7 blocker. Administering E. sativa (1 g kg−1) for 14 days, starting after DNBS injection, contributed to counteracting visceral pain persistence in the post-inflammatory phase of colitis by promoting colon healing from the damage and reducing enteric gliosis. E. sativa defatted seed meal might be employed as a nutraceutical tool for supporting abdominal pain relief in patients.

Highlights

  • The management of patients with inflammatory bowel diseases (IBDs) still represents a therapeutic problem

  • dinitrobenzenesulfonic acid (DNBS) has hasbeen beenreported reportedtototrigger triggeranan enteric glia-mediated inflammatory response in the colon [34], so we investigated whether E. sativa defatted oilseed meal (DSM) might antagonize tory response in the colon [34], so we investigated whether E. sativa DSM might antagothese changes

  • The results obtained in in thethe present work demonstrated thethe beneficial effects of of emThe results obtained present work demonstrated beneficial effects employing in the treatment of colitis-associated persistent abdominal pain and ploying E. sativa DSM in the treatment of colitis-associated persistent abdominal pain and intestinal damage

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Summary

Introduction

The management of patients with inflammatory bowel diseases (IBDs) still represents a therapeutic problem. The complex nature of this type of disease, both inflammatory and neuropathic, makes patients partially responsive to anti-inflammatory drugs, spasmolytics, anticonvulsants, or antidepressants, which are classically used in the management of other pain conditions [1,3]. Glucosinolates (GSLs), phytochemicals peculiar to Brassicaceae, and their hydrolysis-derivatives, isothiocyanates (ITCs), are among the most promising naturally occurring molecules in the treatment of inflammatory and neurological disorders, such as pain [4,5,6,7]. The biological effect of GSLs and their by-products is the result of a series of molecular mechanisms acting simultaneously, such as the modulation of xenobiotic metabolism and the regulation of inflammatory response, apoptosis, and oxidative stress. Recent evidence has attested to the ability of GSLs and ITCs to modulate the activity of channels, namely, Kv7 potassium channels, and receptors involved in pain transmission [4,6]

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