Department of Pharmacy, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Planta Med. 2012 Apr;78(6):565-74. doi: 10.1055/s-0031-1298238. Epub 2012 Feb 3.
Ardipusilloside I, extracted from ARDISIA PUSILLA A.DC, effectively inhibits the progression of several cancers in animal models and is a potential anti-cancer drug candidate. However, the metabolism and pharmacokinetic characteristics of ardipusilloside I remain unknown. In this study, we developed a highly sensitive liquid chromatography-tandem MS method to determine the ardipusilloside I concentration in rat plasma using ginsenoside Re (whose structure is similar to ardipusilloside I) as the internal standard. After oral administration of ardipusilloside I, its four possible metabolites (M1, M2, M3, and M4, whose structures were determined by MS) were detected in the content from rat small intestine. In rat plasma, however, only M3 and M4 were detected after oral administration of ardipusilloside I. None of the metabolites were detected in plasma samples after intravenous administration of ardipusilloside I to rats. These results indicated that the metabolites, but not the drug itself, were absorbed into plasma after oral administration of ardipusilloside I to rats and that M3 and M4 may be responsible for the antitumor activity of orally administered ardipusilloside I in rat models of cancer.
从秀丽紫金牛（ARDISIA PUSILLA A.DC）中提取的 Ardipusilloside I 有效抑制了动物模型中几种癌症的进展，是一种有潜力的抗癌药物候选物。然而， Ardipusilloside I 的代谢和药代动力学特征仍不清楚。在这项研究中，我们开发了一种高灵敏度的液相色谱-串联质谱法，使用结构类似于 Ardipusilloside I 的人参皂苷 Re 作为内标，来测定大鼠血浆中的 Ardipusilloside I 浓度。口服 Ardipusilloside I 后，在大鼠小肠内容物中检测到了它的四个可能的代谢产物（M1、M2、M3 和 M4，其结构通过 MS 确定）。然而，在大鼠口服 Ardipusilloside I 后，仅在血浆中检测到 M3 和 M4。在大鼠静脉注射 Ardipusilloside I 后，在血浆样品中均未检测到代谢产物。这些结果表明，代谢产物（而不是药物本身）在大鼠口服 Ardipusilloside I 后被吸收到血浆中，并且 M3 和 M4 可能是口服 Ardipusilloside I 在癌症大鼠模型中发挥抗肿瘤活性的原因。
