HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Intestinal transport of scutellarein and scutellarin and first-pass metabolism by UDP-glucuronosyltransferase-mediated glucuronidation of scutellarein and hydrolysis of scutellarin.

Abstract
Scutellarin (SG) is a bioactive flavonoid used to treat cardiovascular disease. Scutellarein (S) is the aglycone form of SG. This study aimed to characterize their intestinal transport and first-pass metabolism by UDP-glucuronosyltransferase-mediated glucuronidation and β-glucuronidase-mediated hydrolysis. Results showed that S is more readily passed through Caco-2 cell monolayers by passive diffusion than SG. SG was the predominant metabolite of S, which was formed during the transportation of S across Caco-2 cell monolayers or following incubation of S with human microsomes. SG was extensively generated in human liver microsomes (HLMs), which was demonstrated by its higher catalyzing efficiency (C(lint)) in liver microsomes than in human intestinal microsomes (HIMs). Enzymatic kinetic analysis indicated that the catalyzing efficiency of UGT1A9 was the highest among the tested UGTs under the present experimental conditions, followed by UGT1A1 and UGT1A3. No significant P450-mediated hydroxylation of S was found. SG may be hydrolyzed into S in both HLMs and HIMs.
AuthorsYazhi Wang, Heisio Ao, Zhengming Qian, Ying Zheng
JournalXenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 41 Issue 7 Pg. 538-48 (Jul 2011) ISSN: 1366-5928 [Electronic] England
PMID21561321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glucuronates
  • Glucuronides
  • Isoenzymes
  • Recombinant Proteins
  • scutellarin
  • NADP
  • Apigenin
  • Cytochrome P-450 Enzyme System
  • Glucuronosyltransferase
  • scutellarein
Topics
  • Apigenin (chemistry, metabolism)
  • Biological Transport
  • Biotransformation
  • Caco-2 Cells
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System (metabolism)
  • Glucuronates (chemistry, metabolism)
  • Glucuronides (metabolism)
  • Glucuronosyltransferase (metabolism)
  • Humans
  • Hydrolysis
  • Hydroxylation
  • Intestinal Mucosa (metabolism)
  • Isoenzymes (metabolism)
  • Kinetics
  • Mass Spectrometry
  • Microsomes, Liver (metabolism)
  • NADP (metabolism)
  • Recombinant Proteins (metabolism)
  • Ultraviolet Rays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: