Actin remodeling is a critical regulator of mast cell secretion. In previous work, we have shown that dehydroleucodine and xanthatin, two natural α,β-unsaturated lactones, exhibit anti-inflammatory and mast cell stabilizing properties. Based on this background, this study aimed to determine whether the mast cell stabilizing action of these lactones is associated with changes in the actin cytoskeleton. Rat peritoneal mast cells were preincubated in the presence of dehydroleucodine or xanthatin before incubation with compound 48/80. Comparative studies with sodium cromoglycate and latrunculin B were also made. After treatments, different assays were performed on mast cell samples: β-hexosaminidase release, cell viability studies, quantification of mast cells and their state of degranulation by light microscopy, transmission electron microscopy, and actin staining for microscopy observation. Results showed that dehydroleucodine and xanthatin inhibited mast cell degranulation, evidenced by the inhibition of β-hexosaminidase release and decreased degranulated mast cell percentage. At the same time, both lactones altered the F-actin cytoskeleton in mast cells resulting, similarly to Latrunculin B, in a higher concentration of nuclear F-actin when activated by compound 48/80. For the first time, this study describes the biological properties of dehydroleucodine and xanthatin concerning to the rearrangement of actin filaments during stimulated exocytosis in mast cells. These data have important implications for developing new anti-inflammatory and mast cell stabilizing drugs and for designing new small molecules that may interact with the actin cytoskeleton.

中文翻译：

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脱氢亮古丁和黄黄素是两种天然抗炎内酯，通过影响肌动蛋白细胞骨架来抑制肥大细胞脱颗粒

肌动蛋白重塑是肥大细胞分泌的关键调节因子。在之前的工作中，我们已经证明脱氢亮古丁和黄黄素这两种天然 α,β-不饱和内酯具有抗炎和肥大细胞稳定特性。基于这一背景，本研究旨在确定这些内酯的肥大细胞稳定作用是否与肌动蛋白细胞骨架的变化相关。在与化合物48/80一起温育之前，将大鼠腹膜肥大细胞在脱氢亮古丁或黄黄素的存在下预温育。还进行了色甘酸钠和latrunculin B的比较研究。处理后，对肥大细胞样品进行不同的测定：β-己糖胺酶释放、细胞活力研究、通过光学显微镜、透射电子显微镜和肌动蛋白染色对肥大细胞及其脱颗粒状态进行定量。结果表明，脱氢亮氨酸和黄黄素抑制肥大细胞脱颗粒，这通过抑制 β-己糖胺酶释放并降低脱颗粒肥大细胞百分比来证明。同时，与 Latrunculin B 类似，两种内酯都会改变肥大细胞中的 F-肌动蛋白细胞骨架，当被化合物 48/80 激活时，会产生更高浓度的核 F-肌动蛋白。这项研究首次描述了脱氢亮古丁和黄黄素在肥大细胞中受刺激的胞吐作用期间与肌动蛋白丝重排有关的生物学特性。这些数据对于开发新的抗炎和肥大细胞稳定药物以及设计可能与肌动蛋白细胞骨架相互作用的新小分子具有重要意义。