title: Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides.
abstract: Enterohepatic recycling is often thought to involve mostly phase II metabolites generated in the liver. This study aims to determine if direct biliary excretion of extrahepatically generated glucuronides would also enable recycling.
  
  
  
  Conventional and modified intestinal perfusion models along with intestinal and liver microsomes were used to determine the contribution of extrahepatically derived glucuronides. Glucuronidation of four flavonoids (genistein, biochanin A, apigenin, and chrysin at 2.5-20 μM) were generally more rapid in the hepatic than intestinal microsomes. Furthermore, when aglycones (at 10 μM each) were perfused, larger (1.7-9 fold) amounts of glucuronides were found in the bile than in the luminal perfusate. However, higher concentrations of glucuronides were not found in jugular vein than portal vein, and apigenin glucuronide actually displayed a significantly lower concentration in jugular vein (<1 nM) than portal vein (≈4 nM). A direct portal infusion of four flavonoid glucuronides (5.9-10.4 μM perfused at 2 mL/h) showed that the vast majority (>65%) of the glucuronides (except for biochanin A glucuronide) administered were efficiently excreted into the bile.
  
  
  
  Direct biliary excretion of extrahepatically generated flavonoid glucuronides is a highly efficient clearance mechanism, which should enable enterohepatic recycling of flavonoids without hepatic conjugating enzymes.
authors: Department of Thoracic and Cardiomacrovascular Surgery, Hubei University of Medicine Affiliated Shiyan Taihe Hospital, Shiyan, Hubei, China.|Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Min
authors: M
authors: Zeng
authors: College of Pharmacy, Hubei University of Medicine, Shiyan, Hubei, China.|Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.|Hubei Provincial Technology and Research Center for Comprehensive Development of Medicinal Herbs, Hubei University of Medicine, Shiyan, Hubei, China.|Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China.
authors: Rongjin
authors: R
authors: Sun
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Sumit
authors: S
authors: Basu
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Yong
authors: Y
authors: Ma
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Shufan
authors: S
authors: Ge
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Taijun
authors: T
authors: Yin
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Song
authors: S
authors: Gao
authors: Department of Thoracic and Cardiomacrovascular Surgery, Hubei University of Medicine Affiliated Shiyan Taihe Hospital, Shiyan, Hubei, China.
authors: Jun
authors: J
authors: Zhang
authors: College of Pharmacy, Hubei University of Medicine, Shiyan, Hubei, China.|Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors: Ming
authors: M
authors: Hu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005419:Flavonoids / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000493:pharmacokinetics*; D065669:Hepatobiliary Elimination / Q000187:drug effects*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005419:Flavonoids; D020719:Glucuronides
keywords: Biliary excretion; Efficient; Enterohepatic recycling; Extrahepatically; Flavonoids