Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
J Ethnopharmacol. 2011 Sep 1;137(1):902-8. doi: 10.1016/j.jep.2011.06.047. Epub 2011 Jul 12.
Deoxymiroestrol (DM), a strong phytoestrogen from Pueraria candollei Wall. ex Benth. var. mirifica (family Leguminosae). This plant has long been used in traditional medicine for rejuvenation.
The expression of aryl hydrocarbon receptor-related genes in mouse hepatocytes in primary culture was quantified by real-time RT-PCR and hepatic microsomal P450 activity was assessed by using ethoxyresorufin O-dealkylation.
The mRNA expression of the aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and CYP1A1 was suppressed, whereas that of CYP1B1, estrogen receptor α (ERα), CYP2B9, and glutathione-S-transferase a2 (GSTa2) was increased. The effects of DM on the gene expression depended on treatment period and concentrations, and were similar to those of β-estradiol (E2). DM and E2 at pharmacological concentrations had a marked synergistic effect on CYP1A1 expression after combined treatment with a typical CYP1 inducer, β-naphthoflavone (βNF), at the level of both transcription and enzymatic activity. DM enhanced the inducible mRNA expression of CYP1A1 and CYP1B1 similar to E2. Meanwhile, the expression of ERα mRNA was not affected by βNF, which, on the contrary, completely eliminated the DM-induced mRNA expression of ERα, CYP2B9, and GSTa2.
The findings that DM modified the expression of several metabolism-related genes suggest the need for caution when using health supplements having phytoestrogenic activity.
去氧米古醇（DM），一种来自于葛属植物（Leguminosae）的强植物雌激素。这种植物长期以来一直被用于传统医学中的抗衰老。
通过实时 RT-PCR 定量测定原代培养的小鼠肝细胞中芳烃受体相关基因的表达，并用乙氧基Resorufin O-脱烷基化评估肝微粒体 P450 活性。
芳烃受体（AhR）、AhR 核转位蛋白和 CYP1A1 的 mRNA 表达受到抑制，而 CYP1B1、雌激素受体α（ERα）、CYP2B9 和谷胱甘肽 S-转移酶 a2（GSTa2）的 mRNA 表达增加。DM 对基因表达的影响取决于处理时间和浓度，与β-雌二醇（E2）相似。DM 和 E2 在药理浓度下与典型的 CYP1 诱导剂β-萘黄酮（βNF）联合处理后，对 CYP1A1 表达具有明显的协同作用，表现在转录和酶活性水平上。DM 增强了 CYP1A1 和 CYP1B1 的诱导型 mRNA 表达，类似于 E2。同时，βNF 对 ERα mRNA 的表达没有影响，相反，它完全消除了 DM 诱导的 ERα、CYP2B9 和 GSTa2 的 mRNA 表达。
DM 修饰了几种代谢相关基因的表达，这表明在使用具有植物雌激素活性的保健品时需要谨慎。
