P-Glycoprotein Inhibitory Activity of Lipophilic Constituents of Echinacea pallida Roots in a Human Proximal Tubular Cell Line

Abstract

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-(8Z,13Z)-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 μg/mL.

Abbreviations

Calcein-AM:calcein acetoxymethyl ester

Pgp:P-glycoprotein

Key words

Echinacea pallida - Asteraceae - polyacetylenes - polyenes - HK-2 cells - P-glycoprotein

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