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

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

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • Cyclosporine / pharmacology
  • Daunorubicin / metabolism*
  • Diosgenin / analogs & derivatives
  • Diosgenin / isolation & purification
  • Diosgenin / pharmacology
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Ecdysteroids / isolation & purification
  • Ecdysteroids / pharmacology
  • Ecdysterone / isolation & purification
  • Ecdysterone / pharmacology
  • Humans
  • Immunosuppressive Agents / pharmacology
  • K562 Cells
  • Leukemia / drug therapy
  • Leukemia / metabolism
  • Magnoliopsida / chemistry
  • Membrane Transport Modulators / pharmacology
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rhizome
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Spirostans / isolation & purification
  • Spirostans / pharmacology
  • Steroids / isolation & purification
  • Steroids / pharmacology

Substances

  • 3-O-Rha(1-2)(Ara(1-4))Glc-pennogenine
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Ecdysteroids
  • Immunosuppressive Agents
  • Membrane Transport Modulators
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Plant Extracts
  • Saponins
  • Spirostans
  • Steroids
  • polyphyllin D
  • gracillin
  • Ecdysterone
  • Cyclosporine
  • Diosgenin
  • Daunorubicin