Transport of Alkamides from Echinacea Species through Caco-2 Monolayers[1]

Abstract

To gain more insights into the human intestinal absorption of alkamides from Echinacea species, transport studies were performed with the human adenocarcinoma colonic cell line Caco-2 (ATCC) as a model to assess the epithelial transport of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2). 30 minutes after apical loading of 25 μg/ml 1/2, about 15 % of these alkamides were detectable on the basolateral side. Close monitoring of the transport during 6 hours revealed a nearly complete transport to the basolateral side after 4 hours and no significant metabolism was observable. Transport experiments performed at 4 °C showed only a slight decrease in transport, which is a strong hint that dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2) cross biological membranes by passive diffusion. Nearly the same results were obtained after preincubation of the Caco-2 cells with lipopolysaccharides (LPS) or phorbol 12-myristate-13-acetate (PMA) to mimic an inflammatory status. These results support the assumption that the alkamides can be easily transported from the intestinum and hence may contribute to the in vivo effects of Echinacea preparations.

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1 This article is dedicated in deep gratitude to Prof. Dr. Otto Sticher (ETH Zurich, Institute of Pharmaceutical Sciences) on the occasion of his 65^th birthday.