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

点击翻译按钮获取中文摘要

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.