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重楼甾体皂苷对P-糖蛋白活性的选择性调控

Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla.

作者信息

Nguyen Van Thi Bao, Darbour Nicole, Bayet Christine, Doreau Agnès, Raad Imad, Phung Binh Hoa, Dumontet Charles, Di Pietro Attilio, Dijoux-Franca Marie-Geneviève, Guilet David

机构信息

Université de Lyon, Laboratoire de Pharmacognosie, UMR 5557 CNRS, Faculté de Pharmacie, 8 avenue Rockefeller, 69373 Lyon Cedex 8, France.

出版信息

Fitoterapia. 2009 Jan;80(1):39-42. doi: 10.1016/j.fitote.2008.09.010. Epub 2008 Oct 8.

DOI:10.1016/j.fitote.2008.09.010
PMID:18940238
Abstract

Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(1-->2)[Ara(1-->4)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux.

摘要

基于对K562/R7细胞系中P-糖蛋白介导的柔红霉素外排的抑制作用，对七叶一枝花（延龄草科）根进行生物活性导向的分离，从而分离并鉴定出三种皂苷：3-O-鼠李糖（1→2）[阿拉伯糖（1→4）]葡萄糖-偏诺皂苷元、纤细皂苷和重楼皂苷D，以及两种蜕皮甾体：20-羟基蜕皮酮和羽扇豆甾酮。使用药物筛选细胞系和转染细胞系对这些化合物针对P-糖蛋白（ABCB1）进行多药逆转测试，同时也对乳腺癌耐药蛋白（BCRP/ABCG2）进行测试。与对BCRP的低效作用相反，这三种皂苷作为P-糖蛋白介导的药物外排抑制剂显示出显著效果。

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