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

We have studied interactions in the gastrointestinal tract of flavonoids and the influence of glycosylation on their subsequent metabolism by examining the urinary recoveries of the flavonoid naringenin-7-glucoside and its aglycone, in the conscious rat model, after oral and intravenous administration. Absorption studies were also conducted using an in vitro isolated rat jejunum. The results show that ca. 10% of the administered dose of naringenin 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%) were detected. After intravenous dosing the majority of that identified in the urine was as the native glucoside. These findings suggest that, via the oral route, the glycoside group is cleaved by an intestinal enzyme prior to glucuronidation within the epithelium. This is substantiated by the urinary elimination of the native glucoside and the lack of detection of glucuronide after intravenous administration. Transport studies with isolated intestine showed that neither unchanged naringenin nor the 7-glucoside was absorbed in significant quantities across the gut wall. The major metabolite detected in both cases was naringenin glucuronide, thus supporting the notion that glucuronidation as well as hydrolysis can occur at the intestinal epithelium. (C) 1999 Academic Press.