Deglucuronidation of a flavonoid, luteolin monoglucuronide, during inflammation.

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). beta-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. beta-Glucuronidase activity in human serum from patients on hemodialysis increased significantly compared with that from healthy volunteers. The beta-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 beta-glucuronidase is released from stimulated neutrophils or certain injured cells and then deglucuronidation of flavonoids occurs.