DEVELOPMENT OF NOVEL ASSAY SYSTEM FOR ANTI-ALLERGIC COMPOUNDS FROM NATURAL SOURCES AND APPLICATION

天然来源抗过敏化合物新型检测系统的开发及应用

基本信息

批准号：
17510185
负责人：
ISHIGURO Kyoko
金额：
$ 2.37万
依托单位：
Mukogawa Women's University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17510185/
关键词：
Blood flow monitoring Hen-egg white lysozyme iNOS KO mouse inducible NO synthase (iNOS)e NOS (6) COX-1 and 2 Allergy preventive medicines in vivo assay system in vivoアッセイ法 NO COX-1、2 PGI_2

项目摘要

Our in vivo assay system developed to search for allergy-preventive substances, assesses the blood flow decrease in tail vein microcirculation of mice subjected to sensitization with hen-egg white lysozyme (HEL). The blood flow decrease appears to be regulated by various factors such as nitric oxide (NO), thromboxane (TX) A2, prostacyclin (PGI2) and endothelin (ET)-1 together with cyclooxygenase (COX)-1, 2, and inducible nitric oxide synthase (iNOS).In this study, we examined in detail the roles of iNOS in this assay system using an iNOS knockout (KO) mouse. We found that the blood flow decrease in the HEL-sensitized iNOS KO mice was slightly weaker than that in their wild type (WT) mice. This blood flow decrease was not affected by a selective COX-1 inhibitor, a COX-2 inhibitor and a PGI2 agonist unlike the case of the WT mice. However, it was inhibited by a nonselective NOS inhibitor, a specific TXA2 synthase inhibitor and a specific ET-1 receptor blocker as in the case of the WT mice. The present results indicate that the blood flow decrease occurs via two pathways; one is an iNOS-independent response involving TXA2 and ET-1, and the other is an iNOS-dependent response involving COX-1, COX-2 and PGI2. Constitutive nitric oxide synthase (cNOS) appears to play some roles in the blood flow decrease and iNOS acts as an exacerbation factor. Our method using HEL-sensitized should be useful for searching for agents that can prevent allergy via new mechanisms.The other hand we also demonstrated allergy-preventive activity of extract of Populus sieboldii, Xanthorrhoea hastilis and Lonicera japonica using this in vivo assay system. By bioassay-directed fractionation of these plans, new allergy-preventive compounds were isolated.

我们开发的体内测定系统是为了寻找过敏的物质，评估了用鸡蛋白色溶菌酶（HEL）敏化的小鼠的尾静脉微循环的血流降低。血流量下降似乎受各种因素（例如一氧化氮（NO），动力箱（TX）A2，Prostacyclin（PGI2）（PGI2）和内皮素（ET）-1以及环氧酶（Cox）-1、2，以及可诱导的一氧化氮合酶（Inos）的估算，我们的估算中的nistos ins in nighoins insos nistos insos ins in nighose nistos，（KO）鼠标。我们发现，在狂热的INOS KO小鼠中的血流降低比其野生型（WT）小鼠的血流略有弱。与WT小鼠的情况不同，这种血流降低不受选择性COX-1抑制剂，COX-2抑制剂和PGI2激动剂的影响。然而，与WT小鼠一样，非选择性的NOS抑制剂，特定的TXA2合酶抑制剂和特定的ET-1受体阻滞剂抑制了它。目前的结果表明，血流减少是通过两种途径发生的。一种是涉及TXA2和ET-1的iNOS独立响应，另一个是涉及COX-1，COX-2和PGI2的INOS依赖性响应。组成型一氧化氮合酶（CNOS）似乎在血流降低中起着一些作用，而iNOS充当加重因子。我们使用HEL敏化的方法对于搜索可以通过新机制预防过敏的剂很有用。另一方面，我们还证明了Populus sieboldii，Xanthorrhoea hastilis and lonicera japonica的提取物的过敏性活性。通过对这些计划的生物测定指导的分馏，分离出新的预防过敏化合物。