Aalto Anna L, Saadabadi Atefeh, Lindholm Fanny, Kietz Christa, Himmelroos Emmy, Marimuthu Parthiban, Salo-Ahen Outi M H, Eklund Patrik, Meinander Annika
Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
InFLAMES Research Flagship Center, Åbo Akademi University, Turku, Finland.
Front Immunol. 2023 Sep 22;14:1253805. doi: 10.3389/fimmu.2023.1253805. eCollection 2023.
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).
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).
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.
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 .
已报道芪类化合物在动物模型中具有抗炎特性，并已证明其可通过瞬时受体电位锚蛋白1（TrpA1）抑制Ca2+内流。
为研究芪类化合物如何影响炎症信号传导，我们利用果蝇作为模型系统。为在果蝇中诱导肠道炎症，我们用肠道刺激物葡聚糖硫酸钠（DSS）喂养果蝇。
我们发现DSS会引起果蝇肠道细菌群落的严重变化，且这种生态失调会导致NF-κB转录因子Relish的激活。我们利用DSS模型研究了芪类化合物白皮杉醇（PS）和白皮杉醇单甲醚（PSMME）的抗炎特性。借助相关方法，我们确定PS和PSMME是果蝇中NF-κB介导的肠道免疫反应的瞬时受体锚蛋白1（TrpA1）依赖性拮抗剂。我们还通过计算预测了这些化合物在果蝇TrpA1上的假定拮抗剂结合位点。
综上所述，我们表明芪类化合物PS和PSMME在肠道中具有抗炎特性，可用于减轻果蝇中化学诱导的肠道炎症。
