Planta Med 2013; 79(03/04): 266-274
DOI: 10.1055/s-0032-1328198
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Echinacea sanguinea and Echinacea pallida Extracts Stimulate Glucuronidation and Basolateral Transfer of Bauer Alkamides 8 and 10 and Ketone 24 and Inhibit P-glycoprotein Transporter in Caco-2 Cells

Zhiyi Qiang
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
,
Cathy Hauck
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
,
Joe-Ann McCoy
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
,
Mark P. Widrlechner
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
2   USDA-ARS North Central Regional Plant Introduction Station, Departments of Agronomy and Horticulture, Iowa State University, Ames, IA, USA
,
Manju B. Reddy
3   Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA
,
Patricia A. Murphy
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
,
Suzanne Hendrich
1   The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA, USA
› Author Affiliations
Further Information

Publication History

received 11 July 2012
revised 18 December 2012

accepted 09 January 2013

Publication Date:
13 February 2013 (online)

Abstract

The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator. We hypothesized that Bauer alkamides 8, 10, and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit the P-glycoprotein transporter in Caco-2 human intestinal epithelial cells. Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix. Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11. Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts. Bauer alkamides 8, 10, and 11 (175–230 µM) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~ 90 µM total alkamides) and E. pallida (5 mg/mL, containing 285 µM total alkamides) decreased the efflux of the P-glycoprotein transporter probe calcein-AM from Caco-2 cells. These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits. Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics, which are substrates for the P-glycoprotein transporter.

 
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