Construction of molecular basis and clinical application of Kampo medicine

甘布族药材大黄(Daio)长期以来经常被用作泻药。我们以前曾报道过DAIO能延长线虫的寿命，然而，DAIO对其生物学效应的影响尚不清楚。在本研究中，为了阐明DAIO延长线虫寿命的分子机制，我们利用基因芯片技术筛选了DAIO作用下上调的基因。我们获得了6个被DAIO转录激活10倍以上的基因，并在小鼠身上鉴定了它们在哺乳动物中的同源物。灌胃给药2周后，6个候选基因之一Nhe1在肾脏中的表达上调，与线虫相似。这些发现表明，编码Na/H交换蛋白的Nhe1在维持肾脏的结构和功能方面发挥着重要作用。为了将DAIO用于动物实验，我们还开发了一种制备番泻苷还原DAIO的方法，该方法保留了大多数其他主要成分。

Kampo crude drug, daio (Rhei rhizoma) is frequently used as a purgative for a long time. We previously reported the extending life span of nematode treated with daio, however, its biological response by administration of daio remains unclear. In this study, to clarify the molecular mechanisms on life extension by daio in nematode, we screened the genes upregulated by administration of daio using microarray analysis. We obtained six genes transcriptionally activated more than 10 times by daio and their mammalian homologues were characterized in mice. By 2-week oral administration, expression of Nhe1, one of the six candidate genes, in kidney was upregulated similarly to that in nematode. These findings suggest that the Nhe1 encoding Na+/H+ exchanger protein plays an important role in maintaining kidney structurally and functionally.To use daio in animal experiments, we have also developed a method for preparing sennoside-reduced daio, which maintains most of other major components.