组胺H1受体拮抗剂高通量筛选模型的建立及应用

Establishment and Application of High Throughput Screening Model for H1R Antagonists

组胺H1受体拮抗剂被用于治疗某些过敏性疾病,如鼻炎、荨麻疹和过敏性皮炎。本文采用无标记细胞整合药理学技术建立了组胺H1受体拮抗剂高通量筛选模型。应用基于共振波导光栅的动态质量重置分析方法检测了已知的激动剂和拮抗剂作用于A431细胞上内源性H1受体后所产生的特征信号,获取特征信号谱,建立组胺H1受体拮抗剂筛选模型。进而应用此模型筛选了32个天然产物对组胺H1受体的拮抗活性。结果表明,无标记DMR分析适合于H1受体拮抗剂的高通量筛选;在筛选的32个化合物中,从亚贡中分离得到的内酯类化合物为活性较强的拮抗剂。上述结果表明,无标记DMR分析可能成为组胺H1受体拮抗剂发现的新方法。

The H1R antagonists are used in the treatment of several allergic conditions, such as rhinoconjunctivitis, urti- caria and atopie dermatitis. Here we reported a label-free cell phenotypic profiling model for high throughput screening of H1R antagonists. Resonant waveguide grating enabled dynamic mass redistribution （DMR） assay was used to character- ize the endogenous H1R in A431 cell using known agonists and antagonists. To further identify potential natural products as HIR antagonists,32 natural products were screened using label-free DMR assay. Results showed that label-free DMR assay was suitable for high throughput screening of H1R antagonists ; Among 32 compounds, two lactone compounds which isolated from Smallanthus sonchifolius were found to be more potent antagonist in DMR assay. These results sug- gested that label-free DMR assay might represent a new approach for the discovery of H1R antagonists.