Skip to main content
SpringerLink
Log in

Differential effects of quercetin glycosides on GABAC receptor channel activity

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Quercetin, a representative flavonoid, is a compound of low molecular weight found in various colored plants and vegetables. Quercetin shows a wide range of neuropharmacological activities. In fact, quercetin naturally exists as monomer-(quercetin-3-O-rhamnoside) (Rham1), dimer-(Rutin), or trimer-glycosides [quercetin-3-(2G-rhamnosylrutinoside)] (Rham2) at carbon-3 in fruits and vegetables. The carbohydrate components are removed after ingestion into gastrointestinal systems. The role of the glycosides attached to quercetin in the regulation of γ-aminobutyric acid class C (GABAC) receptor channel activity has not been determined. In the present study, we examined the effects of quercetin glycosides on GABAC receptor channel activity by expressing human GABAC alone in Xenopus oocytes using a two-electrode voltage clamp technique and also compared the effects of quercetin glycosides with quercetin. We found that GABA-induced inward current (I GABA ) was inhibited by quercetin or quercetin glycosides. The inhibitory effects of quercetin and its glycosides on I GABA were concentration-dependent and reversible in the order of Rutin ≈ quercetin ≈ Rham 1 > Rham 2. The inhibitory effects of quercetin and its glycosides on I GABA were noncompetitive and membrane voltage-insensitive. These results indicate that quercetin and its glycosides regulate GABAC receptor channel activity through interaction with a different site from that of GABA, and that the number of carbohydrate attached to quercetin might play an important role in the regulation of GABAC receptor channel activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Azevedo, M.I., A.F. Pereira, R.B. Nogueira, F.E. Rolim, G.A. Brito, D.V. Wong, R.C. Lima-Júnior, R. de Albuquerque Ribeiro, and M.L. Vale. 2013. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Molecular Pain 9(1): 53.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bormann, J., and A. Feigenspan. 1995. GABAC receptors. Trends in Neurosciences 18(12): 9–515.

    Article  Google Scholar 

  • Boue-Grabot, E., A. Taupignon, G. Tramu, and M. Garret. 2000. Molecular and electrophysiological evidence for a GABAc receptor in thyrotropin-secreting cells. Endocrinology 141: 1627–1632.

    CAS  PubMed  Google Scholar 

  • Chebib, M. 2004. GABAC receptor ion channels. Clinical and Experimental Pharmacology and Physiology 31: 800–804.

    Article  CAS  PubMed  Google Scholar 

  • Enz, R., J.H. Brandstätter, H. Wässle, and J. Bormann. 1996. Immunocytochemical localization of the GABAc receptor rho subunits in the mammalian retina. Journal of Neuroscience 16(14): 90–4479.

    Google Scholar 

  • Goutman, J.D., and D.J. Calvo. 2004. Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA rho 1 receptor. British Journal of Pharmacology 141(4): 27–717.

    Article  Google Scholar 

  • Goutman, J.D., M.D. Waxemberg, F. Doñate-Oliver, P.E. Pomata, and D.J. Calvo. 2003. Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors. European Journal of Pharmacology 461(2–3): 79–87.

    Article  CAS  PubMed  Google Scholar 

  • Griebel, G., G. Perrault, S. Tan, H. Schoemaker, and D.J. Sanger. 1999. Pharmacological studies on synthetic flavonoids: comparison with diazepam. Neuropharmacology 38(7): 77–965.

    Article  Google Scholar 

  • Harborne, J.B., and C.A. Williams. 2000. Advances in flavonoid research since 1992. Phytochemistry 55(6): 481–504.

    Article  CAS  PubMed  Google Scholar 

  • Havsteen, B.H. 2002. The biochemistry and medical significance of the flavonoids. Pharmacology and Therapeutics 96(2–3): 67–202.

    Article  CAS  PubMed  Google Scholar 

  • Jansen, A., M. Hoepfner, K.H. Herzig, E.O. Riecken, and H. Scherübl. 2000. GABA(C) receptors in neuroendocrine gut cells: a new GABA-binding site in the gut. Pflugers Archiv. European Journal of Physiology 441: 294–300.

    Article  CAS  PubMed  Google Scholar 

  • Kambe, D., M. Kotani, M. Yoshimoto, S. Kaku, S. Chaki, and K. Honda. 2010. Effects of quercetin on the sleep–wake cycle in rats: involvement of gamma-aminobutyric acid receptor type A in regulation of rapid eye movement sleep. Brain Research 1330: 8–83.

    Article  Google Scholar 

  • Kandaswami, C., and E. Middleton Jr. 1994. Free radical scavenging and antioxidant activity of plant flavonoids. Advances in Experimental Medicine and Biology 66: 76–351.

    Google Scholar 

  • Kyselova, Z., M. Stefek, and V. Bauer. 2004. Pharmacological prevention of diabetic cataract. Journal of Diabetes and Its Complications 18(2): 40–129.

    Article  Google Scholar 

  • Lee, B.H., S.M. Jeong, J.H. Lee, J.H. Kim, I.S. Yoon, J.H. Lee, S.H. Choi, S.M. Lee, C.G. Chang, H.C. Kim, Y. Han, H.D. Paik, Y. Kim, and S.Y. Nah. 2005. Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I. Molecules and Cells 20(1): 69–73.

    CAS  PubMed  Google Scholar 

  • Lee, B.H., J.H. Lee, I.S. Yoon, J.H. Lee, S.H. Choi, M.K. Pyo, S.M. Jeong, W.S. Choi, T.J. Shin, S.M. Lee, H. Rhim, Y.S. Park, Y.S. Han, H.D. Paik, S.G. Cho, C.H. Kim, Y.H. Lim, and S.Y. Nah. 2007. Human glycine alpha1 receptor inhibition by quercetin is abolished or inversed by alpha267 mutations in transmembrane domain 2. Brain Research 1161: 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Lukasiewicz, P.D., and F.S. Werblin. 1994. A novel GABA receptor modulates synaptic transmission from bipolar to ganglion and amacrine cells in the tiger salamander retina. Journal of Neuroscience 14: 23–1213.

    Google Scholar 

  • Macdonald, R.L., and R.W. Olsen. 1994. GABAA receptor channels. Annual Review of Neuroscience 17: 569–602.

    Article  CAS  PubMed  Google Scholar 

  • Marder, M., H. Viola, C. Wasowski, C. Wolfman, P.G. Waterman, B.K. Cassels, J.G. Medina, and A.C. Paladini. 1996. 6-Bromoflavone, a high affinity ligand for the central benzodiazepine receptors is a member of a family of active flavonoids. Biochemical and Biophysical Research Communications 223(2): 9–384.

    Article  Google Scholar 

  • Medina, J.H., H. Viola, C. Wolfman, M. Marder, C. Wasowski, D. Calvo, and A.C. Paladini. 1997. Overview—flavonoids: a new family of benzodiazepine receptor ligands. Neurochemical Research 22(4): 25–419.

    Article  Google Scholar 

  • Miksicek, R.J. 1993. In situ localization of the estrogen receptor in living cells with the fluorescent phytoestrogen coumestrol. Journal of Histochemistry and Cytochemistry 41(6): 10–801.

    Article  Google Scholar 

  • Nilsson, E., and B. Eyrich. 1950. On treatment of barbiturate poisoning. Acta Medica Scandinavica 137(6): 381–389.

    Article  CAS  PubMed  Google Scholar 

  • Oyama, Y., P.A. Fuchs, N. Katayama, and K. Noda. 1994. Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons. Brain Research 635(1–2): 9–125.

    Google Scholar 

  • Picq, M., S.L. Cheav, and A.F. Prigent. 1991. Effect of two flavonoid compounds on central nervous system. Analgesic activity. Life Sciences 49(26): 88–1979.

    Article  Google Scholar 

  • Polenzani, L., R.M. Woodward, and R. Miledi. 1991. Expression of mammalian gamma-aminobutyric acid receptors with distinct pharmacology in Xenopus oocytes. Proceedings of the National Academy of Sciences of the United States of America 88(10): 22–4318.

    Article  Google Scholar 

  • Pyo, M.K., Y.K. Koo, and H.S. Yun-Choi. 2002. Anti-platelet effect of the phenolic constituents isolated from the leaves of Magnolia obovata. Nat Prod Sci 8(4): 147–151.

  • Sine, S.M., and P. Taylor. 1982. Local anesthetics and histrionicotoxin are allosteric inhibitors of the acetylcholine receptor. Studies of clonal muscle cells. Journal of Biological Chemistry 257(14): 104–8106.

    Google Scholar 

  • Speroni, E., and A. Minghetti. 1988. Neuropharmacological activity of extracts from Passiflora incarnata. Planta Medica 54(6): 91–488.

    Article  Google Scholar 

  • Stefek, M., and C. Karasu. 2011. Eye lens in aging and diabetes: effect of quercetin. Rejuvenation Res 14(5): 34–525.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Basic Science Research Program (2011-0021144) and the Priority Research Centers Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science, and Technology (2012-0006686) and by the BK21 plus project fund to S.-Y. Nah.

Author information

Authors and Affiliations

  1. Department of Physiology, College of Veterinary Medicine and BioMolecular Informatics Center, Konkuk University, Seoul, 143-701, Korea

    Hyeon-Joong Kim, Byung-Hwan Lee, Sun-Hye Choi, Seok-Won Jung, Hyun-Sook Kim & Seung-Yeol Nah

  2. Department of Physical Therapy, College of Health Science, Cheongju University, Chungbuk, 360-764, Korea

    Joon-Hee Lee

  3. Department of Pharmaceutical Engineering, Sangji University, Wonju, 220-702, Korea

    Sung-Hee Hwang

  4. International Ginseng and Herb Research Institute, Geumsan, 312-804, Korea

    Mi-Kyung Pyo

  5. Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea

    Hyoung-Chun Kim

Authors
  1. Hyeon-Joong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byung-Hwan Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sun-Hye Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seok-Won Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyun-Sook Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joon-Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sung-Hee Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mi-Kyung Pyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hyoung-Chun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Seung-Yeol Nah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seung-Yeol Nah.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 51 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, HJ., Lee, BH., Choi, SH. et al. Differential effects of quercetin glycosides on GABAC receptor channel activity. Arch. Pharm. Res. 38, 108–114 (2015). https://doi.org/10.1007/s12272-014-0409-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-014-0409-2

Keywords

Search

Navigation