In vitro transport and uptake of protohypericin and hypericin in the Caco-2 model

The intestinal absorption characteristics of protohypericin, a protonaphtho dianthrone present in Hypericum extract, were studied and compared with tho se of hypericin. The Caco-2 model was used as a model of the intestinal muc osa to assess transepithelial transport and cell uptake. The experimental w ork was performed in specific light conditions that prevented both the phot oconversion of protohypericin into hypericin and the photosensitization of the cells. Following application of the individual compounds (80-200 mu M) to the apical side of the monolayers, the appearance in the basolateral com partment was found to be very low (< 0.5%/5 h), but was comparable for both compounds. A lag-time of 2-3 h was observed, suggesting gradual saturation of binding sites on the membrane or inside the cells. Uptake experiments o f protohypericin and hypericin by Caco-2 cells revealed a very significant cellular accumulation (4-8%); uptake was characterised by saturation after 3 h. The findings of this study suggest that protohypericin has comparable absorption characteristics as hypericin and may contribute to the beneficia l effect of Hypericum extract after oral dosing. (C) 1999 Published by Else vier Science B.V. All rights reserved.