Enteric disposition and recycling of flavonoids and Ginkgo flavonoids

Objective: The objective of this study was to determine the intestinal and microbial disposition of flavonoids and how these disposition processes affect their enteric recycling. Design: Studies were performed using a perfused rat intestinal model or using enrichment cultures and a pure isolate of Enterococcus avium (LY1). Results: In the rat intestine, aglycones, such as quercetin and apigenin, were as permeable (P-eff(*) greater than or equal to 2) as compounds such as propranolol (100% absorption). However, a significant portion of the absorbed aglycones was conjugated and the metabolites were excreted into the lumen. Flavonoid glycosides, such as isoquercitrin and apigenin-7-O-glucoside, also had high apparent P*eff values (? 2) in the upper small intestine because of rapid hydrolysis. However, isoquercitrin was absorbed much slower (P-eff(*) less than or equal to 0.7, p < 0.05) when hydrolysis was absent or inhibited by 20 mmol gluconolactone. Absorption of other intact glycosides was similar to intact isoquercitrin and was much slower than the corresponding aglycones (P-eff(*) less than or equal to 0.7, p < 0.05). Intestinal bacteria, such as LY1, hydrolyzed the flavonoid glycosides used in the study. Excreted glycosidases were involved in the hydrolysis of glycosides because glycosides were poorly taken up by LY1. In conclusion, glycosidase-catalyzed hydrolysis is a critical first step in the intestinal and microbial disposition of flavonoid glycosides. Aglycones were not only rapidly absorbed, but also rapidly metabolized into phase II conjugates, which were then excreted back into the lumen. Therefore, intestinal and microbial glycosidases and intestinal phase II enzymes make a significant contribution to the disposition of flavonoids via the proposed enteric and enterohepatic recycling scheme.