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