RT Journal Article
SR Electronic
T1 Deglucuronidation of a Flavonoid, Luteolin Monoglucuronide, during Inflammation
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1521
OP 1524
VO 29
IS 12
A1 Shimoi, Kayoko
A1 Saka, Noriko
A1 Nozawa, Ryushi
A1 Sato, Motoyoshi
A1 Amano, Izumi
A1 Nakayama, Tsutomu
A1 Kinae, Naohide
YR 2001
UL http://dmd.aspetjournals.org/content/29/12/1521.abstract
AB In this study, we investigated whether luteolin monoglucuronide was converted to free aglycone during inflammation using human neutrophils stimulated with ionomycin/cytochalasin B and rats treated with lipopolysaccharide (LPS). β-Glucuronidase activity was assayed using 4-methylumbelliferyl-glucuronide and methanol extracts of rat plasma containing luteolin monoglucuronide. The released 4-methylumbelliferone, a fluorescent molecule, was quantified by fluorometry. Deglucuronidation of luteolin monoglucuronide was examined by high-performance liquid chromatography (HPLC) analysis. HPLC analyses showed that the supernatants obtained from neutrophils stimulated with ionomycin/cytochalasin B hydrolyzed luteolin monoglucuronide to free luteolin. β-Glucuronidase activity in human serum from patients on hemodialysis increased significantly compared with that from healthy volunteers. The β-glucuronidase activity in rat plasma increased after i.v. injection of LPS. The ratio of luteolin to luteolin monoglucuronide in plasma of LPS-treated rats also increased. These results suggest that during inflammation β-glucuronidase is released from stimulated neutrophils or certain injured cells and then deglucuronidation of flavonoids occurs. The American Society for Pharmacology and Experimental Therapeutics