title: Inhibitory effect of anthocyanidins on hepatic glutathione S-transferase, UDP-glucuronosyltransferase and carbonyl reductase activities in rat and human.
abstract: 1. Anthocyanins and their aglycone anthocyanidins represent the most abundant flavonoids in human diet and popular constituents of various dietary supplements. The aim of this study was to evaluate inhibitory effect of four anthocyanidins (delphinidin, cyanidin, malvidin and pelargonidin) on three families of important drug-metabolizing enzymes: carbonyl reductases (CBRs), glutathione S-transferases (GSTs) and UDP-glucuronosyltransferases (UGT). 2. Human or rat hepatic subcellular fractions were incubated with or without pure anthocyanidins (100 µM) and the activities of CBR, GST and UGT were assayed using menadione, 1-chloro-2,4-dinitrobenzene and p-nitrophenol as substrates, respectively. For the most potent inhibitors, half maximal inhibitory concentrations (IC50) were determined and the inhibition kinetics study was performed. 3. Anthocyanidins inhibited weakly the activity of GST and moderately the activities of CBR and UGT. Cyanidin was the most potent inhibitor of human UGT with IC50 = 69 µM (at 200 µM substrate concentration) and competitive type of action. Delphinidin acted as significant non-competitive inhibitor of human CBR with IC50 = 16 µM (at substrate concentration 500 µM). The inhibitory potency of anthocyanidins differed in rat and human samples significantly. 4. Anthocyanidins are able to inhibit CBR and UGT in vitro. Possible interference of anthocyanidins (in high-dose dietary supplements) with simultaneously administered drugs, which are UGT or CBR substrates, should be checked.
authors: Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského, Hradec Králové, Czech Republic.
authors: Barbora
authors: B
authors: Szotáková
authors: Hana
authors: H
authors: Bártíková
authors: Jitka
authors: J
authors: Hlaváčová
authors: Iva
authors: I
authors: Boušová
authors: Lenka
authors: L
authors: Skálová
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
chemical_list: D000872:Anthocyanins; D004791:Enzyme Inhibitors; D000429:Alcohol Oxidoreductases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase