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.
Shimoi
K
K
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan. shimoi@smail.u-shizuoka-ken.ac.jp
Saka
N
N
Nozawa
R
R
Sato
M
M
Amano
I
I
Nakayama
T
T
Kinae
N
N
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003571:Cytochalasin B / Q000494:pharmacology; D005100:Expectorants / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D047311:Luteolin; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005100:Expectorants; D005419:Flavonoids; D020719:Glucuronides; D007476:Ionophores; D008070:Lipopolysaccharides; D003571:Cytochalasin B; D015759:Ionomycin; D005966:Glucuronidase; D047311:Luteolin