Stilbenoid compounds inhibit NF-κB-mediated inflammatory responses in the intestine.

INTRODUCTION

Stilbenoid compounds have been described to have anti-inflammatory properties in animal models , and have been shown to inhibit Ca2+-influx through the transient receptor potential ankyrin 1 (TrpA1).

METHODS

To study how stilbenoid compounds affect inflammatory signaling , we have utilized the fruit fly, , as a model system. To induce intestinal inflammation in the fly, we have fed flies with the intestinal irritant dextran sodium sulphate (DSS).

RESULTS

We found that DSS induces severe changes in the bacteriome of the intestine, and that this dysbiosis causes activation of the NF-κB transcription factor Relish. We have taken advantage of the DSS-model to study the anti-inflammatory properties of the stilbenoid compounds pinosylvin (PS) and pinosylvin monomethyl ether (PSMME). With the help of approaches, we have identified PS and PSMME to be transient receptor ankyrin 1 (TrpA1)-dependent antagonists of NF-κB-mediated intestinal immune responses in . We have also computationally predicted the putative antagonist binding sites of these compounds at TrpA1.

DISCUSSION

Taken together, we show that the stilbenoids PS and PSMME have anti-inflammatory properties in the intestine and can be used to alleviate chemically induced intestinal inflammation in .