Lee D H, Cho I G, Park M S, Kim K N, Chang I M, Mar W
Natural Products Research Institute, Seoul National University, Korea.
Arch Pharm Res. 2001 Feb;24(1):55-63. doi: 10.1007/BF02976494.
Aucubin, an iridoid glucoside, was investigated to determine whether it has a stimulating effect on alpha-amanitin excretion in alpha-amanitin intoxicated rats, and whether there is binding activity to calf thymus DNA. High-performance liquid chromatography (HPLC) analysis of alpha-amanitin in rat urine allowed quantitative measurement of the alpha-amanitin concentration with a detection limit of 50 ng/ml. In this system, a group treated with both alpha-amanitin and aucubin showed that alpha-amanitin was excreted about 1.4 times faster than in the alpha-amanitin only treated group. Our previous results showed that the toxicity of alpha-amanitin is due to specific inhibition of RNA polymerase activity and the resultant blockage of the synthesis of certain RNA species in the nucleus. However, no significant activity change on RNA polymerase from Hep G2 cells was observed when aucubin was treated with alpha-amanitin at any concentration tested. Nevertheless, aucubigenin inhibited both DNA polymerase (IC50, 80.5 microg/ml) and RNA polymerase (IC50, 135.0 microg/ml) from the Hep G2 cells. The potential of both alpha-amanitin and aucubin to interact with DNA were examined by spectrophotometric analysis. Alpha-Amanitin showed no significant binding capacity to calf thymus DNA, but aucubin was found to interact with DNA, and the apparent binding constant (Kapp) and apparent number of binding sites per DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively.
桃叶珊瑚苷，一种环烯醚萜苷，被研究以确定它是否对α-鹅膏毒肽中毒的大鼠的α-鹅膏毒肽排泄有刺激作用，以及是否与小牛胸腺DNA有结合活性。通过高效液相色谱（HPLC）分析大鼠尿液中的α-鹅膏毒肽，可以定量测量α-鹅膏毒肽浓度，检测限为50 ng/ml。在这个系统中，用α-鹅膏毒肽和桃叶珊瑚苷共同处理的一组显示，α-鹅膏毒肽的排泄速度比仅用α-鹅膏毒肽处理的组快约1.4倍。我们之前的结果表明，α-鹅膏毒肽的毒性是由于对RNA聚合酶活性的特异性抑制以及由此导致的细胞核中某些RNA种类合成的阻断。然而，当用任何测试浓度的桃叶珊瑚苷与α-鹅膏毒肽处理时，未观察到来自Hep G2细胞的RNA聚合酶有显著的活性变化。尽管如此，桃叶珊瑚苷元抑制了来自Hep G2细胞的DNA聚合酶（IC50，80.5 μg/ml）和RNA聚合酶（IC50，135.0 μg/ml）。通过分光光度分析检查了α-鹅膏毒肽和桃叶珊瑚苷与DNA相互作用的潜力。α-鹅膏毒肽对小牛胸腺DNA没有显著的结合能力，但发现桃叶珊瑚苷与DNA相互作用，表观结合常数（Kapp）和每个DNA磷酸的表观结合位点数（Bapp）分别为0.45×10⁴ M⁻¹和1.25。
