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.

• Anthocyanidins
• carbonyl reductase
• flavonoids
• glutathione S-transferase
• inhibition kinetics
• species differences
• UDP-glucuronosyltransferase