Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine

Abstract

1. Quercetin is a natural flavonoid present in vegetables, fruit and wine, and is known to inhibit sulphotransferase. Drugs are often taken orally and the intestinal mucosa is an early site of drug metabolism. The aims of this investigation were to study the inhibition of dopamine, (-)-salbutamol, minoxidil and paracetamol sulphation by quercetin in the duodenal mucosa and liver and to compare the IC 50 in these tissues. 2. The rates (pmol min -1 mg -1) of sulphation of 4-nitrophenol were 343 92 (liver) and 164 22 (duodenum; p = 0.031), of dopamine were 15 11 (liver) and 656 516 (duodenum; p = 0.049), of (-)-salbutamol were 153 31 (liver) and 654 277 (duodenum; p = 0.018), of minoxidil were 156 47 (liver) and 105 7 (duodenum; n.s.), and of paracetamol were 229 86 (liver) and 328 187 (duodenum; n.s.). 3. The IC 50 of quercetin for 4-nitrophenol was 48 11 nM (liver) and 56 1 nM (duodenum, n.s.), for dopamine was 5.7 0.7 µM (liver) and 170 12µM (duodenum, p < 0.0001), for (-)-salbutamol was 54 4 nM (liver) and 16 8µM (duodenum; p = 0.025), for minoxidil was 134 22 nM (liver) and 3 0.3 µM (duodenum, p = 0.013), and for paracetamol was 57 7 nM (liver) and 35 1 µM (duodenum; p = 0.0002). 4. Quercetin inhibited the sulphation of 4-nitrophenol, dopamine, (-)-salbutamol, minoxidil and paracetamol both in liver and duodenum. With dopamine, (-)-salbutamol, minoxidil and paracetamol as substrates, quercetin was a more potent inhibitor in the liver than the duodenum. Such a difference may reflect the different composition of sulphotransferase forms in the liver and duodenum.