Development of anti-allergics against antianaphylaxis type by lead-optimization

从小叶Ehretia microphylla分离得到的微叶虫素在_□M浓度下对RBL-2H3细胞的胞外分泌有抑制作用。测定了微叶黄酮作为一种新型抗过敏化合物的理化和生物学特性。微叶黄酮不仅能抑制RBL-2H3细胞的胞吐，还能在各种刺激下抑制大鼠肥大细胞和人嗜碱性细胞的胞吐。微叶黄酮通过刺激抑制细胞内钙离子浓度的增加，这是由于抑制钙通过钙释放活化钙（CRAC）通道流入。此外，我们在以下过敏模型中确定了微叶黄酮的作用。微叶黄酮抑制被动皮肤过敏反应和蛔虫诱导的双相皮肤过敏反应的即时期。另一方面，微phyllone对晚期蛔虫诱导的双相皮肤过敏反应和恶唑酮诱导的接触型延迟皮肤反应等iv型过敏模式没有影响。微叶黄酮可作为新型抗过敏药和/或新型抗急性过敏反应的先导化合物。

Microphyllone isolated from Ehretia microphylla has the inhibitory activity on exocytosis in RBL-2H3 cells at _□M concentration. We have determined the physicochemical and biological characters of microphyllone as a novel anti-allergic compound. Microphyllone inhibited exocytosis not only in RBL-2H3 cells but also in rat mast cells, and human basophiles with various stimuli. Microphyllone inhibited an increase in concentration of intracellular calcium ion by stimulation, which is due to inhibition of calcium influx through calcium release-activated calcium (CRAC) channel. We, furthermore, determine the effects of microphyllone in the following allergic models. Microphyllone suppressed passive cutaneous anaphylaxis reaction and immediate phase of ascaris-induced biphasic skin allergic reaction. On the other hand, microphyllone has no effect on type-IV allergic modes such as late phase of ascaris-induced biphasic skin allergic reaction and oxazolone-induced contact type delayed cutaneous reaction. Microphyllone can be a new type of anti-allergics and/or a lead compound for new class anti-allergics against acute allergic reactions.