P-Glycoprotein inhibitory activity of lipophilic constituents of Echinacea pallida roots in a human proximal tubular cell line.
The N-hexane root extracts from Echinacea pallida, Echinacea angustifolia and Echinacea purpurea were evaluated for inhibition of the multidrug transporter P-glycoprotein (Pgp) activity, the product of the ABCB1 gene, involved in cancer multidrug resistance (MDR) and in herb-drug or drug-drug interactions. The biological assay was performed using the human proximal tubule HK-2 cell line that constitutively expresses ABCB1. The N-hexane extracts of all three species reduced the efflux of the Pgp probe calcein-AM from HK-2 cells two-fold in a concentration-dependent manner, and E. pallida was found to be the most active species. For the first time, two polyacetylenes and three polyenes, isolated from the N-hexane extract of E. pallida roots by a bioassay-guided fractionation, were found to be able to reduce Pgp activity. Pentadeca-(8 Z,13 Z)-dien-11-yn-2-one was the most efficient compound, being able to decrease the calcein-AM efflux about three-fold with respect to the control at 30 microg/mL.
Romiti
Nadia
N
Department of Experimental Pathology, The School of Medicine, University of Pisa, via Roma 55, Pisa, Italy.
Pellati
Federica
F
Nieri
Paola
P
Benvenuti
Stefania
S
Adinolfi
Barbara
B
Chieli
Elisabetta
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D002460:Cell Line; D020900:Echinacea; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts