Introduction

Mast cells are involved in not only inducing, but also maintaining neurogenic inflammation and neuropathic pain. In previous work, we have demonstrated that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit rat peritoneal and human LAD2 mast cell degranulation induced by compound 48/80 and calcium ionophore A23187. However, the effect of these molecules on neuropeptide-induced mast cell activation has not been studied so far.

Objective

The aim of this study was to determine whether dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one inhibit neuropeptide-induced mast cell activation.

Methods

This work is based on in vitro simulation of a neurogenic inflammation scenario involving neuropeptides and mast cells, to subsequently analyze potential therapeutic strategies for neuropathic pain.

Results

Neuromedin-N did not stimulate mast cell serotonin release but substance P and neurotensin did induce serotonin release from peritoneal mast cells in a dose-dependent manner. Mast cell serotonin release induced by substance P and neurotensin was inhibited by dehydroleucodine and xanthatin, but not by 3-benzyloxymethyl-5H-furan-2-one. The inhibitory potency of dehydroleucodine and xanthatin was higher than that obtained with the reference compounds, ketotifen and sodium chromoglycate, when mast cells were preincubated with dehydroleucodine before substance P incubation, and with dehydroleucodine or xanthatin before neurotensin incubation.

Conclusions

These results are the first strong evidence supporting the hypothesis that dehydroleucodine and xanthatin inhibit substance P- and neurotensin-induced serotonin release from rat peritoneal mast cells. Our findings suggest, additionally, that these α,β-unsaturated lactones could be of value in future pharmacological research related to inappropriate mast cell activation conditions such as neurogenic inflammation and neuropathic pain.

中文翻译：

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天然 α,β-不饱和内酯在神经源性炎症的体外模型中抑制神经肽诱导的肥大细胞活化。

介绍

肥大细胞不仅参与诱导，而且参与维持神经源性炎症和神经性疼痛。在以前的工作中，我们已经证明脱氢亮氨酸、黄原素和 3-benzyloxymethyl-5 H -furan-2-one 抑制由化合物 48/80 和钙离子载体 A23187 诱导的大鼠腹膜和人 LAD2 肥大细胞脱粒。然而，迄今为止尚未研究这些分子对神经肽诱导的肥大细胞活化的影响。

客观的

本研究的目的是确定脱氢亮氨酸、黄原素和 3-benzyloxymethyl-5 H - furan -2-one 是否抑制神经肽诱导的肥大细胞活化。

方法

这项工作基于对涉及神经肽和肥大细胞的神经源性炎症场景的体外模拟，以随后分析神经性疼痛的潜在治疗策略。

结果

Neuromedin-N 不刺激肥大细胞血清素释放，但P物质和神经降压素确实以剂量依赖性方式诱导腹膜肥大细胞释放血清素。由P物质和神经降压素诱导的肥大细胞 5-羟色胺释放被脱氢亮氨酸和黄原素抑制，但不受 3-苄氧基甲基-5 H-呋喃-2-one 的抑制。当肥大细胞在P物质孵育前与脱氢亮氨酸预孵育时，以及在神经降压素孵育前与脱氢亮氨酸或黄原素预孵育时，脱氢亮氨酸和黄原素的抑制效力高于使用参比化合物酮替芬和铬甘酸钠获得的抑制效力。

结论

这些结果是支持脱氢亮氨酸和黄原素抑制P物质和神经降压素诱导的大鼠腹膜肥大细胞释放血清素的假设的第一个有力证据。此外，我们的研究结果表明，这些α,β-不饱和内酯在未来与不适当的肥大细胞激活条件（如神经源性炎症和神经性疼痛）相关的药理学研究中可能具有价值。