Document Detail


A novel local recycling mechanism that enhances enteric bioavailability of flavonoids and prolongs their residence time in the gut.
MedLine Citation:
PMID:  23033922     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Bijun Xia; Qiong Zhou; Zhijie Zheng; Ling Ye; Ming Hu; Zhongqiu Liu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-24
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  9     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-04-30     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3246-58     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / pharmacology
Biological Availability
Caco-2 Cells
Flavanones / metabolism*,  pharmacokinetics
Gastrointestinal Tract / drug effects,  metabolism*
Glucaric Acid / analogs & derivatives,  pharmacology
Gluconates / pharmacology
Glucuronidase / antagonists & inhibitors,  metabolism
Glucuronides / metabolism*,  pharmacokinetics
Humans
Intestinal Absorption / drug effects
Jejunum / drug effects,  metabolism
Kinetics
Lactase-Phlorizin Hydrolase / antagonists & inhibitors,  metabolism
Lactones / pharmacology
Male
Rats
Rats, Sprague-Dawley
Recycling
Tandem Mass Spectrometry
Tissue Distribution
Grant Support
ID/Acronym/Agency:
GM70737/GM/NIGMS NIH HHS; R01 GM070737/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Flavanones; 0/Gluconates; 0/Glucuronides; 0/Lactones; 0/wogonin-7-glucuronide; 5027-63-4/saccharolactone; 632-85-9/wogonin; EC 3.2.1.31/Glucuronidase; EC 3.2.1.62/Lactase-Phlorizin Hydrolase; QLZ991V4A2/Glucaric Acid; WQ29KQ9POT/beta-glucono-1,5-lactone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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