Differential Effects of Quercetin and Quercetin Glycosides on Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of alpha 7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I-ACh) in Xenopus oocytes expressing the alpha 7 nAChR. I-ACh was measured with a two-electrode voltage clamp technique. In oocytes injected with alpha 7 nAChR copy RNA, quercetin enhanced I-ACh, whereas quercetin glycosides inhibited I-ACh. Quercetin glycosides mediated an inhibition of I-ACh, which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I-ACh inhibition by quercetin glycosides was Rutin >= Rham1>Rham2. Quercetin glycosides -mediated lath enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I-ACh, inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated alpha 7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the alpha 7 nAChR in a differential manner.