Uptake of Quercetin and Quercetin 3-Glucoside from Whole Onion and Apple Peel Extracts by Caco-2 Cell Monolayers JEANELLE BOYER, † DAN BROWN, † AND RUI HAI LIU* ,§ Departments of Food Science and Animal Science, Cornell University, Ithaca, New York 14853-7201 Evidence suggests that regular consumption of fruits and vegetables may reduce the risk of chronic diseases, and phytochemicals from fruits and vegetables may be responsible for this health benefit. However, there is limited knowledge on the bioavailability of specific phytochemicals from whole fruits and vegetables. This study used Caco-2 cells to examine uptake of quercetin aglycon and quercetin 3-glucoside as purified compounds and from whole onion and apple peel extracts. Pure quercetin aglycon was absorbed by the Caco-2 cells in higher concentrations than quercetin 3-glucoside (p < 0.05). Caco-2 cells treated with quercetin 3-glucoside accumulated both quercetin 3-glucoside and quercetin. Caco-2 cells absorbed more onion quercetin aglycon than onion quercetin 3-glucoside (p < 0.05), and the percentage of onion quercetin absorbed was greater than that of pure quercetin, most likely due to enzymatic hydrolysis of quercetin 3-glucoside and other quercetin glucosides found in the onion by the Caco-2 cells. Caco-2 cells absorbed low levels of quercetin 3-glucoside from apple peel extracts, but quercetin aglycon absorption was not detected. Caco-2 cell homogenates demonstrated both lactase and glucosidase activities when incubated with lactose and quercetin 3-glucoside, respectively. This use of the Caco2 cell model appears to be a simple and useful system for studying bioavailability of whole food phytochemicals and may be used to assess differences in bioavailability between foods. KEYWORDS: Quercetin; phenolics; flavonoids; cell culture; apple; onion INTRODUCTION Epidemiological studies have shown that the ingestion of diets high in fruits and vegetables may decrease the risk of cancer and cardiovascular disease (1, 2). Much of the protective effects of fruits and vegetables has been attributed to phytochemicals, possibly due to their ability to protect against oxidative stress (3). A major class of phytochemicals found commonly in fruits and vegetables are the flavonoids, and the most common flavonoids found in fruits and vegetables are quercetin and its conjugates (4). Flavonoid intake, particularly quercetin, has been inversely associated with incidences of heart disease, cere- brovascular disease, and several types of cancer (5). Other studies have also shown an inverse relationship between coronary heart disease and flavonoid intake, particularly when adults consumed apples, onions, and tea, foods high in quercetin conjugates (6-8). Although some groups have found links between flavonoids and cancer (9, 10), others have found no relationship (11). This discrepancy appears to be more common when researchers seek to identify correlations between a specific, isolated compound or class of compounds and reduced cancer risk (1). However, there is strong evidence supporting a lower cancer risk associated with diets high in fruits and vegetables, and this correlation may be due to a complex combination of phytochemicals rather than the action of a single compound (12). To this date, little literature exists that addresses the bio- availability of phytochemicals from whole foods. The use of human and animal clinical trials for studying bioavailability is complex, time-consuming, and expensive. Alternatively, in vitro models are attractive options due to their potential overall simplicity and lower cost. We selected a well-established in vitro model that uses the Caco-2 cell line. The Caco-2 cells are derived from human adenocarcinoma and will differentiate into polarized enterocyte-like monolayers, acting similarly to intes- tinal epithelial cells. The model has been developed for pharmaceutical assay and more recently used for micronutrient assay (13). It has been used to evaluate cell transport and/or accumulation of pure phytochemicals such as quercetin, quer- cetin glucosides, chrysin, flavone, epicatechin, and proantho- cyanidin (14-20), as well as to estimate carotenoid bioavail- ability from fresh stir-fried vegetables and from spinach puree (21, 22). Understanding the bioavailability of pure compounds is a necessary start to understanding the bioavailability of these same compounds when present as a complex mixture of phytochemi- cals within whole fruits and vegetables. The latter is more complicated because many factors, such as concentrations and forms of individual phytochemicals, interactions with other chemicals in the food, and the properties of the food matrix * Author to whom correspondence should be addressed [telephone (607) 255-6235; fax (607) 254-4868; e-mail RL23@cornell.edu]. † Department of Animal Science. § Department of Food Science. 7172 J. Agric. Food Chem. 2004, 52, 7172-7179 10.1021/jf030733d CCC: $27.50 © 2004 American Chemical Society Published on Web 10/16/2004