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 α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 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 (IACh) in Xenopus oocytes expressing the α7 nAChR. IACh was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced IACh, whereas quercetin glycosides inhibited IACh. Quercetin glycosides mediated an inhibition of IACh, which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of IACh inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated IACh enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated IACh inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 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 α7 nAChR in a differential manner.
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Byung-Hwan
BH
Lee
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Sun-Hye
SH
Choi
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Hyeon-Joong
HJ
Kim
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Seok-Won
SW
Jung
Department of Pharmaceutical Engineering, Sangji University, Wonju 26339, Republic of Korea.
Sung-Hee
SH
Hwang
International Ginseng and Herb Research Institute, Geumsan 32724, Republic of Korea.
Mi-Kyung
MK
Pyo
Life Science Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Hyewhon
H
Rhim
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
Hyoung-Chun
HC
Kim
Mibyeong Research Center, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Ho-Kyoung
HK
Kim
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Sang-Mok
SM
Lee
Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
Seung-Yeol
SY
Nah
Flavonoids; Quercetin; Quercetin glycosides; α7 nAChR