In Vitro Absorption and Metabolism of a Citrus Chemopreventive Agent, Auraptene, and Its Modifying Effects on Xenobiotic Enzyme Activities in Mouse Livers

Abstract: We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely occurring in citrus fruit, is a structurally novel type of effective cancer-preventive agent, as manifested in several rodent models. However, its bioavailability and metabolism in biological systems have yet to be investigated. In the present study, we examined the chemical stability of AUR at pH 1.57 and 37°C (as a stomach digestion model) and observed its stoichiometric conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t1/2) = 15 h; 7-ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human colorectal adenocarcinoma cell line, were used as a small intestine model. ETC permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent manner; AUR slightly permeated the cells, but with an intracellular accumulation. Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9 mixture. ETC was also converted to UMB, but its t1/2 of two hours was much sh...