Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Sinomenine, an Alkaloid Derived from Sinomenium acutum Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep in Rodents

  • Yoo, Jae Hyeon (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Ha, Tae-Woo (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Hong, Jin Tae (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Oh, Ki-Wan (College of Pharmacy and Medical Research Center, Chungbuk National University)
  • Received : 2017.08.07
  • Accepted : 2017.09.07
  • Published : 2017.11.01
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Abstract

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

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References

  1. Abourashed, E. A., Koetter, U. and Brattstrom, A. (2004) In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine 11, 633-638. https://doi.org/10.1016/j.phymed.2004.03.005
  2. Bao, G. H., Qin, G. W., Wang, R. and Tang, X. C. (2005) Morphinane alkaloids with cell protective effects from Sinomenium acutum. J. Nat. Prod. 68, 1128-1130. https://doi.org/10.1021/np050112+
  3. Bu, D. F., Erlander, M. G., Hitz, B. C., Tillakaratne, N. J., Kaufman, D. L., Wagner-McPherson, C. B., Evans, G. A. and Tobin, A. J. (1992) Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc. Natl. Acad. Sci. U.S.A. 89, 2115-2119. https://doi.org/10.1073/pnas.89.6.2115
  4. Chen, Y.-J., Shiao, M. S., Lee, S. S. and Wang, S. Y. (1997) Effect of Cordyceps sinensis on the proliferation and differentiation of human leukemic U937 cells. Life Sci. 60, 2349-2359. https://doi.org/10.1016/S0024-3205(97)00291-9
  5. Collinson, N., Kuenzi, F. M., Jarolimek, W., Maubach, K. A., Cothliff, R., Sur, C., Smith, A., Otu, F. M., Howell, O., Atack, J. R., McKernan, R. M., Seabrook, G. R., Dawson, G. R., Whiting, P. J. and Rosahl, T. W. (2002) Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the $GABA_A$ receptor. J. Neurosci. 22, 5572-5580. https://doi.org/10.1523/JNEUROSCI.22-13-05572.2002
  6. Crestani, F., Keist, R., Fritschy, J. M., Benke, D., Vogt, K., Prut, L., Bluthmann, H., Mohler, H. and Rudolph, U. (2002) Trace fear conditioning involves hippocampal ${\alpha}_5$ $GABA_A$ receptors. Proc. Natl. Acad. Sci. U.S.A. 99, 8980-8985. https://doi.org/10.1073/pnas.142288699
  7. Crestani, F., Low, K., Keist, R., Mandelli, M., Mohler, H. and Rudolph, U. (2001) Molecular targets for the myorelaxant action of diazepam. Mol. Pharmacol. 59, 442-445. https://doi.org/10.1124/mol.59.3.442
  8. Datta, S. and Hobson, J. A. (2000) The rat as an experimental model for sleep neurophysiology. Behav. Neurosci. 114, 1239-1244. https://doi.org/10.1037/0735-7044.114.6.1239
  9. Gottesmann, C. (1996) The transition from slow-wave sleep to paradoxical sleep: evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep. Neurosci. Biobehav. Rev. 20, 367-387. https://doi.org/10.1016/0149-7634(95)00055-0
  10. Han, S., Niu, W., Li, H., Hu, L., Yuan, Y. and Xu, G. (2010) Effect of hydroxyl and amino groups on electrochemiluminescence activity of tertiary amines at low tris(2,2'-bipyridyl)ruthenium(II) concentrations. Talanta 81, 44-47. https://doi.org/10.1016/j.talanta.2009.11.037
  11. Hu, Z., Kim, C.-S., Oh, E. H., Lee, M. K., Eun, J. S., Hong, J. T. and Oh, K. W. (2012) Methanol extract of zizyphi spinosi semen augments pentobarbital-induced sleep through the modification of GABAergic systems. Nat. Prod. Sci. 18, 67-75.
  12. Jin, H. Z., Wang, X. L., Wang, H. B., Wang, Y. B., Lin, L. P., Ding, J. and Qin, G. W. (2008) Morphinane alkaloid dimers from Sinomenium acutum. J. Nat. Prod. 71, 127-129. https://doi.org/10.1021/np0704654
  13. Kim, C. S., Han, J. Y., Kim, S., Hong, J. T. and Oh, K. W. (2011) Herbs for the treatment of insomnia. Biomol. Ther. (Seoul) 19, 274-281. https://doi.org/10.4062/biomolther.2011.19.3.274
  14. Li, S. P., Zhao, K. J., Ji, Z. N., Song, Z. H., Dong, T. T., Lo, C. K., Cheung, J. K., Zhu, S. Q. and Tsim, K. W. (2003) A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury. Life Sci. 73, 2503-2513. https://doi.org/10.1016/S0024-3205(03)00652-0
  15. Low, K., Crestani, F., Keist, R., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., Rulicke, T., Bluethmann, H., Mohler, H. and Rudolph, U. (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290, 131-134. https://doi.org/10.1126/science.290.5489.131
  16. Ma, Y., Eun, J. S., Lee, K. S., Lee, E. S., Kim, C. S., Hwang, B. Y. and Oh, K. W. (2009) Methanol extract of longanae arillus regulates sleep architecture and EEG power spectra in restraint-stressed rats. Nat. Prod. Sci. 15, 213-221.
  17. Ma, Y., Han, H., Eun, J. S., Kim, H. C., Hong, J. T. and Oh, K. W. (2007) Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems. Biol. Pharm. Bull. 30, 1748-1753. https://doi.org/10.1248/bpb.30.1748
  18. Macdonald, R. L. and Olsen, R. W. (1994) $GABA_A$ receptor channels. Annu. Rev. Neurosci. 17, 569-602. https://doi.org/10.1146/annurev.ne.17.030194.003033
  19. McCarley, R. W. (2007) Neurobiology of REM and NREM sleep. Sleep Med. 8, 302-330. https://doi.org/10.1016/j.sleep.2007.03.005
  20. McKernan, R. M., Rosahl, T. W., Reynolds, D. S., Sur, C., Wafford, K. A., Atack, J. R., Farrar, S., Myers, J., Cook, G., Ferris, P., Garrett, L., Bristow, L., Marshall, G., Macaulay, A., Brown, N., Howell, O., Moore, K. W., Carling, R. W., Street, L. J., Castro, J. L., Ragan, C. I., Dawson, G. R. and Whiting, P. J. (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the $GABA_A$ receptor ${\alpha}1$ subtype. Nat. Neurosci. 3, 587-592. https://doi.org/10.1038/75761
  21. Morton, G. J., Kaiyala, K. J., Fisher, J. D., Ogimoto, K., Schwartz, M. W. and Wisse, B. E. (2011) Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice. Am. J. Physiol. Endocrinol. Metab. 300, E392-E401. https://doi.org/10.1152/ajpendo.00546.2010
  22. Paxinos, G., Watson, C., Pennisi, M. and Topple, A. (1985) Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J. Neurosci. Methods 13, 139-143. https://doi.org/10.1016/0165-0270(85)90026-3
  23. Rao, S., Liu, S., Zou, L., Jia, T., Zhao, S., Wu, B., Yi, Z., Wang, S., Xue, Y., Gao, Y., Xu, C., Li, G., Xu, H., Zhang, C. and Liang, S. (2017) The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia. Purinergic Signal. 13, 227-235. https://doi.org/10.1007/s11302-016-9554-z
  24. Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., Martin, J. R., Bluethmann, H. and Mohler, H. (1999) Benzodiazepine actions mediated by specific ${\gamma}$-aminobutyric acidA receptor subtypes. Nature 401, 796-800. https://doi.org/10.1038/44579
  25. Rudolph, U. and Mohler, H. (2006) GABA-based therapeutic approaches: $GABA_A$ receptor subtype functions. Curr. Opin. Pharmacol. 6, 18-23. https://doi.org/10.1016/j.coph.2005.10.003
  26. Sanford, L. D., Yang, L., Liu, X. and Tang, X. (2006) Effects of tetrodotoxin (TTX) inactivation of the central nucleus of the amygdala (CNA) on dark period sleep and activity. Brain Res. 1084, 80-88. https://doi.org/10.1016/j.brainres.2006.02.020
  27. Seifi, M., Brown, J. F., Mills, J., Bhandari, P., Belelli, D., Lambert, J. J., Rudolph, U. and Swinny, J. D. (2014) Molecular and functional diversity of GABA-A receptors in the enteric nervous system of the mouse colon. J. Neurosci. 34, 10361-10378. https://doi.org/10.1523/JNEUROSCI.0441-14.2014
  28. Siegel, J. M. (2005) Clues to the functions of mammalian sleep. Nature 437, 1264-1271. https://doi.org/10.1038/nature04285
  29. Sieghart, W. (1995) Structure and pharmacology of ${\gamma}$-aminobutyric acidA receptor subtypes. Pharmacol. Rev. 47, 181-234.
  30. Tillakaratne, N. J., Medina-Kauwe, L. and Gibson, K. M. (1995) ${\gamma}$-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Comp. Biochem. Physiol. A Physiol. 112, 247-263. https://doi.org/10.1016/0300-9629(95)00099-2
  31. Tokunaga, S., Takeda, Y., Niimoto, T., Nishida, N., Kubo, T., Ohno, T., Matsuura, Y., Kawahara, Y., Shinomiya, K. and Kamei, C. (2007) Effect of valerian extract preparation (BIM) on the sleep-wake cycle in rats. Biol. Pharm. Bull. 30, 363-366. https://doi.org/10.1248/bpb.30.363
  32. Trachsel, L., Tobler, I., Achermann, P. and Borbély, A. A. (1991) Sleep continuity and the REM-nonREM cycle in the rat under baseline conditions and after sleep deprivation. Physiol. Behav. 49, 575-580. https://doi.org/10.1016/0031-9384(91)90283-T
  33. Wagner, C., Vargas, A. P., Roos, D. H., Morel, A. F., Farina, M., Nogueira, C. W., Aschner, M. and Rocha, J. B. (2010) Comparative study of quercetin and its two glycoside derivatives quercitrin and rutin against methylmercury (MeHg)-induced ROS production in rat brain slices. Arch. Toxicol. 84, 89-97. https://doi.org/10.1007/s00204-009-0482-3
  34. Wang, W. and Xu, T. L. (2006) Chloride homeostasis differentially affects $GABA_A$ receptor- and glycine receptor-mediated effects on spontaneous circuit activity in hippocampal cell culture. Neurosci. Lett. 406, 11-16. https://doi.org/10.1016/j.neulet.2006.06.064
  35. Wang, X., Jin, H., Li, Z. and Qin, G. (2007) 8-demethoxyrunanine from Sinomenium acutum. Fitoterapia 78, 593-595. https://doi.org/10.1016/j.fitote.2007.03.018
  36. West, M. R. and Molloy, C. R. (1996) A microplate assay measuring chloride ion channel activity. Anal. Biochem. 241, 51-58. https://doi.org/10.1006/abio.1996.0377
  37. Wolfman, C., Viola, H., Marder, M., Wasowski, C., Ardenghi, P., Izquierdo, I., Paladini, A. C. and Medina, J. H. (1996) Anxioselective properties of 6,3'-dinitroflavone, a high-affinity benzodiazepine receptor ligand. Eur. J. Pharmacol. 318, 23-30. https://doi.org/10.1016/S0014-2999(96)00784-4
  38. Zhu, Q., Sun, Y., Zhu, J., Fang, T., Zhang, W. and Li, J. X. (2014) Antinociceptive effects of sinomenine in a rat model of neuropathic pain. Sci. Rep. 4, 7270.

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