4,8-Sphingadienines (SD), metabolites of glucosylceramides (GlcCer), are sometimes determined as key mediators of the biological activity of dietary GlcCer, and cis/trans geometries of 4,8-SD have been reported to affect its activity. Since regulating excessive activation of mast cells seems an important way to ameliorate allergic diseases, this study was focused on cis/trans stereoisomeric-dependent inhibitory effects of 4,8-SD on mast cell activation. Degranulation of RBL-2H3 was inhibited by treatment of 4-cis-8-trans- and 4-cis-8-cis-SD, and their intradermal administrations ameliorated ear edema in passive cutaneous anaphylaxis reaction, but 4-trans-8-trans- and 4-trans-8-cis-SD did not. Although the activation of mast cells depends on the bound IgE contents, those stereoisomers did not affect IgE contents on RBL-2H3 cells after the sensitization of anti-TNP IgE. These results indicated that 4-cis-8-trans- and 4-cis-8-cis-SD directly inhibit the activation of mast cells. In conclusion, it was assumed that 4,8-SD stereoisomers with cis double bond at C4-position shows anti-allergic activity by inhibiting downstream pathway after activation by the binding of IgE to mast cells.

4,8-鞘氨醇 (SD) 是葡萄糖神经酰胺 (GlcCer) 的代谢物，有时被确定为膳食 GlcCer 生物活性的关键介质，据报道 4,8-SD 的顺式/反式几何结构会影响其活性。由于调节肥大细胞的过度激活似乎是改善过敏性疾病的重要方法，因此本研究重点关注 4,8-SD 对肥大细胞激活的顺式/反式立体异构依赖性抑制作用。 4- cis -8- trans - 和 4- cis -8- cis -SD 治疗可抑制 RBL-2H3 的脱颗粒，并且皮内给药可改善被动皮肤过敏反应中的耳部水肿，但 4- trans -8- trans - 和 4-反式-8-顺式-SD 没有。尽管肥大细胞的激活取决于结合的IgE含量，但这些立体异构体在抗TNP IgE致敏后并不影响RBL-2H3细胞上的IgE含量。这些结果表明4-顺式-8-反式和4-顺式-8-顺式-SD直接抑制肥大细胞的活化。总之，推测C4位具有顺式双键的4,8-SD立体异构体通过IgE与肥大细胞结合激活后抑制下游途径而显示出抗过敏活性。