Molecular dissection of a medicinal herb and identification of target genes by oligonucleotide microarray

从植物、动物和其他天然来源中提取的物质可能可用作药物。自古以来，这些天然物质就被应用于医疗实践，尽管有些经验性。人们相信，在医疗实践中使用天然物质将会增加。然而，大多数草药是各种已知和未知成分的复杂混合物。因此，目前尚不清楚复杂草药中的单个分子如何发挥生物效应并与其他分子相互作用。因此，很难准确地理解草药的生理作用，因为它们含有一系列复杂的组成分子。本研究利用12600个基因的DNA微阵列数据，检测了黄连及其8个组成分子对8种人胰腺癌细胞系的抗增殖活性。我们鉴定出27个基因在暴露72 h后显示出与根茎50%抑制剂量（ID50）密切相关。对这27C基因表达水平的相关系数进行层次聚类分析。根瘤相关基因和每个组成分子的ID50将这些测试分子分为两个簇，一个由根瘤和小檗碱组成，另一个由其余7个分子组成。我们的研究结果表明，一种分子，小檗碱，可以解释大部分的抗增殖活性，DNA微阵列分析可以用来提高我们对一种完整草本植物的作用的理解。

Substances derived from plants, animals and other natural sources may be useful as medicinal drugs. Since ancient times, such natural substances have been applied to medical practice, albeit somewhat empirically. It is believed that use of natural substances in medical practice will increase. However, most herbal medicines are complex mixtures of a variety of known and unknown constituents. Therefore, it remains unclear how a single molecule in a complex herbal medicines exerts a biological effect and interacts with other molecules. Thus, it is difficult to understand precisely the physiological actions of herbs because they contain a complex array of constituent molecules.In this study we used DNA microarray data for 12600 genes to examine the anti-proliferative activity of the herb Coptidis rhizoma and eight constituent molecules against eight human pancreatic cancer cell lines. We identified 27 genes showing strong correlation with the 50% inhibitory dose (ID50) of C. rhizoma after 72-h exposure. Hierarchical cluster analysis with correlation coefficients between expression levels of these 27C. rhizoma-related genes and the ID50 of each constituent molecule classified these test molecules into two clusters, one consisting of C. rhizoma and berberine and the other consisting of the remaining seven molecules. Our results suggest that one molecule, berberine, can account for the majority of the anti-proliferative activity of C. rhizoma and that DNA microarray analyses can be used to improve our understanding of the actions of an intact herb.