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

van Thi Bao Nguyen (1, 2) , Nicole Darbour (1) , Christine Bayet (1) , A. Doreau (3) , Imad Raad (1) , B.H. Phung (2) , C. Dumontet , A. Di Pietro , Marie-Genevieve Dijoux-Franca (1) , David Guilet (1)

1 LEM - Laboratoire d'Ecologie Microbienne - UMR 5557
2 Hanoi University of Pharmacy
3 MMSB - Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry

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(12)[Ara(14)]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.

Mots clés: Rhizome; Saponins; Spirostans; Steroids; Humans; Drug Resistance; Multiple; Leukemia; Angiosperms; ATP-Binding Cassette Transporters; Cyclosporine; Daunorubicin; Diosgenin; Ecdysteroids; Ecdysterone; Immunosuppressive Agents; K562 Cells; Membrane Transport Modulators; Multidrug Resistance-Associated Proteins; Neoplasm; Neoplasm Proteins; P-Glycoprotein; Plant Extracts

Domaines: Sciences pharmaceutiques; Chimie analytique

van Thi Bao Nguyen, Nicole Darbour, Christine Bayet, A. Doreau, Imad Raad, et al.. Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla. Fitoterapia, 2009, 80 (1), pp.39-42. ⟨10.1016/j.fitote.2008.09.010⟩. ⟨hal-02545047⟩