Search for naturally occurring retinoic acid receptor agonists and thier application to immune and allergic diseases

维甲酸受体(RAR)激动剂被认为具有多种免疫调节作用，本研究利用许多Kampo药材和其他药用植物中常用的生药来探索RAR激动剂。我们分离了三个二萜和一个叶黄素作为RAR激动剂，它们具有与以前报道的RAR激动剂不同的结构。新的RAR激动剂和众所周知的RAR激动剂全反式维甲酸(ATRA)之间的基因表达谱存在差异。从生药中提取的RAR激动剂能有效抑制卵清蛋白诱导的食物过敏模型小鼠的腹泻，并呈剂量依赖关系，而从生药中分离出的85%纯RAR激动剂不具有这种抗过敏作用。由于本研究中发现的新的RAR激动剂表现出与ATRA不同的作用，因此，他们的深入研究将有助于将新的RAR激动剂有益于免疫和过敏性疾病。

Agonists for retinoic acid receptor (RAR), which are expected to show various immuno-modulating effects, were explored in the present study using the crude drugs frequently used in many Kampo medicines and other medicinal plants. We isolated three diterpenes and one xanthophyll as RAR agonists, which possess the different structures from those of previously reported RAR agonists. Gene expression profiles were varied between the new RAR agonists and a well-known RAR agonist all-trans retinoic acid (ATRA). The extract of the crude drug, from which an RAR agonist was isolated, effectively suppressed the diarrhea of ovalbumin-induced food allergy model mice in a dose-dependent manner, while 85% pure RAR agonist isolated from a crude drug failed to show such anti-allergic effect. Since new RAR agonists found in this study show the effects distinct from those of ATRA, their intense study will help to apply new RAR agonist beneficially to immune and allergic diseases.