title: A novel local recycling mechanism that enhances enteric bioavailability of flavonoids and prolongs their residence time in the gut.
abstract: Recycling in the gastrointestinal tract is important for endogenous substances such as bile acids and for xenobiotics such as flavonoids. Although both enterohepatic and enteric recycling mechanisms are well recognized, no one has discussed the third recycling mechanism for glucuronides: local recycling. The intestinal absorption and metabolism of wogonin and wogonoside (wogonin-7-glucuronide) was characterized by using a four-site perfused rat intestinal model, and hydrolysis of wogonoside was measured in various enzyme preparations. In the perfusion model, the wogonoside and wogonin were interconverted in all four perfused segments. Absorption of wogonoside and conversion to its aglycon at the upper small intestine was inhibited in the presence of a glucuronidase inhibitor (saccharolactone) but was not inhibited by lactase phlorizin hydrolase (LPH) inhibitor gluconolactone or antibiotics. Further investigation indicated that hydrolysis of wogonoside in the blank intestinal perfusate was not correlated with bacterial counts. Kinetic studies indicated that K(m) values from blank duodenal and jejunal perfusate were essentially identical to the K(m) values from intestinal S9 fraction but were much higher (>2-fold) than those from the microbial enzyme extract. Lastly, jejunal perfusate and S9 fraction share the same optimal pH, which was different from those of fecal extract. In conclusion, local recycling of wogonin and wogonoside is the first demonstrated example that this novel mechanism is functional in the upper small intestine without significant contribution from bacteria β-glucuronidase.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, 1838 N Guangzhou Avenue, Guangzhou, Guangdong 510515, China.
authors.forename: Bijun
authors.initials: B
authors.lastname: Xia
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zheng
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001682:Biological Availability; D018938:Caco-2 Cells; D044950:Flavanones / Q000378:metabolism* / Q000493:pharmacokinetics; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005942:Gluconates / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D010694:Lactase-Phlorizin Hydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D059027:Recycling; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D044950:Flavanones; D005942:Gluconates; D020719:Glucuronides; D007783:Lactones; C465289:wogonin-7-glucuronide; C009194:saccharolactone; D005966:Glucuronidase; D010694:Lactase-Phlorizin Hydrolase; C085514:wogonin; D005937:Glucaric Acid; C010730:beta-glucono-1,5-lactone