Methanol Extract of Zizyphi Spinosi Semen Augments Pentobarbital-Induced Sleep through the Modification of GABAergic Systems

  • Hu, Zhenzhen (College of Pharmac, Chungbuk National University) ;
  • Kim, Chung-Soo (College of Pharmac, Chungbuk National University) ;
  • Oh, Eun-Hye (Department of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Lee, Mi-Kyung (College of Pharmacy, Woosuk University) ;
  • Eun, Jae-Soon (College of Pharmacy, Woosuk University) ;
  • Hong, Jin-Tae (College of Pharmac, Chungbuk National University) ;
  • Oh, Ki-Wan (College of Pharmac, Chungbuk National University)
  • Received : 2012.02.04
  • Accepted : 2012.04.10
  • Published : 2012.06.30

Abstract

Zizyphi Spinosi Semen (ZSS) have been widely used for the treatment of insomnia in Asia. This experiment was performed to investigate whether methanol extract of ZSS (MEZSS) has hypnotic effects through the ${\gamma}$-amino butyric acid (GABA)ergic systems. MEZSS inhibited the locomotor activity. MEZSS enhanced pentobarbital-induced sleep behaviors. However, MEZSS itself did not induce sleep at higher dose, similar to muscimol. On the other hand, both pentobarbital and MEZSS increased the non rapid eye move (NREM) sleep, especially reducing the -wave electroencephalogram (EEG) activity in REM sleep. MEZSS showed similar effects with muscimol on potentiating chloride influx induced by pentobarbital. MEZSS significantly increased GABAA receptors ${\gamma}$-subunit expression and slightly decreased ${\beta}$-subunit expression in hypothalamus and thalamus, showing that subunit-expression was similar to diazepam. In addition, MEZSS enhanced the expression of glutamic acid decarboxylase (GAD). In conclusion, it is suggested that MEZSS might augment pentobarbital-induced sleep behaviors through the modification of GABAergic systems.

Keywords

References

  1. Cao, J.X., Zhang, Q.Y., Cui, S.Y., Cui, X.Y., Zhang, J., Zhang, Y.H. et al Hypnoticeffect of jujubosides from Semen Ziziphi Spinosae. Journal of Ethnopharmacology 130, 163-166 (2010). https://doi.org/10.1016/j.jep.2010.03.023
  2. Doghramji, K. The epidemiology and diagnosis of insomnia. American Journal of Managed Care 12, 214 (2006).
  3. Eun, J.S., Bae, K., Yun, Y.P., Hong, J.T., Kwon, H.N., and Oh, K.W., Inhibitory effects of paeonol on morphine-induced locomotor sensitization and conditioned place preference in mice. Archives of Pharmacal Research 29, 904-910 (2006). https://doi.org/10.1007/BF02973913
  4. Fang, X., Hao, J.F., Zhou, H.Y., Zhu, L.X., Wang, J.H., and Song, F.Q., Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine 17, 75-80 (2010). https://doi.org/10.1016/j.phymed.2009.07.004
  5. Guevara, M., Ramos, J., Hernandez-Gonzalez, M., Zarabozo, D., and Corsi-Cabrera, M., POTENCOR: a program to calculate power and correlation spectra of EEG signals. Computer Methods and Programs in Biomedicine 72, 241-250 (2003). https://doi.org/10.1016/S0169-2607(02)00128-1
  6. Han, H.S., Ma, Y., Eun, J.S., Hong, J.T., and Oh, K.W., Anxiolytic-like effects of cyclopeptide fration alkaloids of zizyphi spinosi semen: possible involvement of $GABA_A$ receptors. Biomolecules & Therapeutics 16, 261-269 (2008). https://doi.org/10.4062/biomolther.2008.16.3.261
  7. Houston, C.M. and Smart, T.G., CaMK-II modulation of GABA(A) receptors expressed in HEK293, NG108-15 and rat cerebellar granule neurons. European Journal of Neuroscience 24, 2504-2514 (2006). https://doi.org/10.1111/j.1460-9568.2006.05145.x
  8. Johnston, G.A., GABAA receptor pharmacology. Pharmacology and Therapeutics 69, 173-198 (1996). https://doi.org/10.1016/0163-7258(95)02043-8
  9. Kim, J.W., Han, J.Y., Hong, J.T., Li, R., Eun, J.S., and Oh, K.W., Ethanol Extract of the Flower Chrysanthemum morifolium Augments Pentobarbital-Induced Sleep Behaviors: Involvement of Cl- Channel Activation. Evidence-based Complementary and Alternative Medicine: eCAM 2011 (2011).
  10. Le Croueour, G., Thepenier, P., Richard, B., Petermann, C., Ghedira, K., and Zeches-Hanrot, M., Lotusine G: a new cyclopeptide alkaloid from Zizyphus lotus. Fitoterapia 73, 63-68 (2002). https://doi.org/10.1016/S0367-326X(01)00363-X
  11. Lee, S.M., Park, J.G., Lee, Y.H., Lee, C.G., Min, B.S., Kim, J.H. et al., Anti-complementary activity of triterpenoides from fruits of Zizyphus jujuba. Biological and Pharmaceutical Bulletin 27, 1883-1886 (2004). https://doi.org/10.1248/bpb.27.1883
  12. Liu, J., Chen, B., and Yao, S., Simultaneous analysis and identification of main bioactive constituents in extract of Zizyphus jujuba var. sapinosa (Zizyphi spinosi semen) by high-performance liquid chromatography-photodiode array detection-electrospray mass spectrometry. Talanta 71, 668-675 (2007). https://doi.org/10.1016/j.talanta.2006.05.014
  13. Ma, Y., Han, H., Eun, J.S., Kim, H.C., Hong, J.T., and Oh, K.W., Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems. Biological and Pharmaceutical Bulletin 30, 1748-1753 (2007). https://doi.org/10.1248/bpb.30.1748
  14. Ma, Y., Ma, H., Jo, Y.J., Kim, D.S., Woo, S.S., and Li, R., Honokiol potentiates pentobarbital-induced sleeping behaviors through $GABA_A$ Receptor $Cl^-$ Channel activation. Biomolecules & Therapeutics 16, 328-335 (2008). https://doi.org/10.4062/biomolther.2008.16.4.328
  15. Murillo-Rodriguez, E., Arias-Carrion, O., Sanguino-Rodriguez, K., Gonzalez-Arias, M., and Haro, R., Mechanisms of sleep-wake cycle modulation. CNS Neurol Disord Drug Targets 8, 245-253 (2009). https://doi.org/10.2174/187152709788921654
  16. Park, J.H., Lee, H.J., Koh, S.B., Ban, J.Y., and Seong, Y.H., Protection of NMDA-induced neuronal cell damage by methanol extract of zizyphi spinosi semen in cultured rat cerebellar granule cells. Journal of Ethnopharmacology 95, 39-45 (2004). https://doi.org/10.1016/j.jep.2004.06.011
  17. Park, K.S., Oh, J.H., Yoo, H.S., Lee, Y.M., Lee, M.K., Hong, J.T. et al., (-)-Epigallocatechin-3-O-gallate (EGCG) reverses caffeine-induced anxiogenic-like effects. Neuroscience Letters 481, 131-134 (2010). https://doi.org/10.1016/j.neulet.2010.06.072
  18. Sapin, E., Berod, A., Leger, L., Herman, P.A., Luppi, P.H., and Peyron, C., A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia. PLoS One 5, e11766 (2010). https://doi.org/10.1371/journal.pone.0011766
  19. Suksamrarn, S., Panseeta, P., Kunchanawatta, S., Distaporn, T., Ruktasing, S., and Suksamrarn, A., Ceanothane- and lupane-type triterpenes with antiplasmodial and antimycobacterial activities from Ziziphus cambodiana. Chemical and Pharmaceutical Bulletin 54, 535-537 (2006). https://doi.org/10.1248/cpb.54.535
  20. Vale, C., Fonfria, E., Bujons, J., Messeguer, A., Rodriguez-Farre, E., and Sunol, C., The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience 117, 397-403 (2003). https://doi.org/10.1016/S0306-4522(02)00875-8
  21. Wang, G.H., Jiang, Z.L., Fan, X.J., Zhang, L., Li, X., and Ke, K.F., Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors. Neuropharmacology 52, 1199-1209 (2007). https://doi.org/10.1016/j.neuropharm.2006.10.022
  22. Wang, L.E., Bai, Y.J., Shi, X.R., Cui, X.Y., Cui, S.Y., Zhang, F. et al., Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system. Pharmacology, Biochemistry and Behavior 90, 399-403 (2008). https://doi.org/10.1016/j.pbb.2008.03.022
  23. Wang, L.E., Cui, X.Y., Cui, S.Y., Cao, J.X., Zhang, J., Zhang, Y.H. et al., Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors. Phytomedicine 17, 404-409 (2010). https://doi.org/10.1016/j.phymed.2010.01.014
  24. West, M.R. and Molloy, C.R., A microplate assay measuring chloride ion channel activity. Analytical Biochemistry 241, 51-58 (1996). https://doi.org/10.1006/abio.1996.0377
  25. Winsky-Sommerer, R., Role of GABAA receptors in the physiology and pharmacology of sleep. European Journal of Neuroscience 29, 1779-1794 (2009). https://doi.org/10.1111/j.1460-9568.2009.06716.x
  26. Wu, X.Y., Zhao, J.L., Zhang, M., Li, F., Zhao, T., and Yang, L.Q., Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum. Journal of Ethnopharmacology 135, 325-329 (2011). https://doi.org/10.1016/j.jep.2011.03.016
  27. Yi, P.L., Lin, C.P., Tsai, C.H., Lin, J.G., and Chang, F.C., The involvement of serotonin receptors in suanzaorentang-induced sleep alteration. Journal of Biomedical Science 14, 829-840 (2007). https://doi.org/10.1007/s11373-007-9197-8
  28. Yi, P.L., Tsai, C.H., Chen, Y.C., and Chang, F.C., Gamma-aminobutyric acid (GABA) receptor mediates suanzaorentang, a traditional Chinese herb remedy, -induced sleep alteration. Journal of Biomedical Science 14, 285-297 (2007). https://doi.org/10.1007/s11373-006-9137-z
  29. Yoon, S.R., Jo, Y.J., Yang, S., Kim, Y.B., Nam, S.Y., Kim, H.C. et al., Sanjoinine A isolated from Semen Zizyphi Spinosi protects against kainic acid-induced convulsions. Archives of Pharmacal Research 32, 1515-1523 (2009). https://doi.org/10.1007/s12272-009-2103-3
  30. Zhang, M., Ning, G., Shou, C., Lu, Y., Hong, D., and Zheng, X., Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Medica 69, 692-695 (2003). https://doi.org/10.1055/s-2003-42786
  31. Zhang, M., Zhang, Y., and Xie, J., Simultaneous determination of jujuboside A, B and betulinic acid in semen Ziziphi spinosae by high performance liquid chromatography-evaporative light scattering detection. Journal of Pharmaceutical and Biomedical Analysis 48, 1467-1470 (2008). https://doi.org/10.1016/j.jpba.2008.09.022