Interactions of the flavonoid naringenin in the gastrointestinal tract andthe influence of glycosylation

We have studied interactions in the gastrointestinal tract of flavonoids an d the influence of glycosylation on their subsequent metabolism by examinin g the urinary recoveries of the flavonoid naringenin-7-glucoside and its ag lycone, in the conscious rat model, after oral and intravenous administrati on. Absorption studies were also conducted using an in vitro isolated rat j ejunum. The results show that ca. 10% of the administered dose of naringeni n was recovered after oral dosing, the majority as naringenin glucuronide, whereas, after intravenous administration, the recovery of the glucuronide was ca. 20%. In contrast, after oral dosing of naringenin-7-glucoside, its hydrolysis product naringenin (0.5%) and naringenin glucuronide (12.7%) wer e detected. After intravenous dosing the majority of that identified in the urine was as the native glucoside. These findings suggest that, via the or al route, the glycoside group is cleaved by an intestinal enzyme prior to g lucuronidation within the epithelium. This is substantiated by the urinary elimination of the native glucoside and the lack of detection of glucuronid e after intravenous administration. Transport studies with isolated intesti ne showed that neither unchanged naringenin nor the 7-glucoside was absorbe d in significant quantities across the gut wall. The major metabolite detec ted in both cases was naringenin glucuronide, thus supporting the notion th at glucuronidation as well as hydrolysis can occur at the intestinal epithe lium. (C) 1999 Academic Press.