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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

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      https://www.riss.kr/link?id=A104735685

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      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 γ-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 (GAD65/67) and GABAA receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through GABAA-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.
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      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 Sinome...

      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 γ-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 (GAD65/67) and GABAA receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through GABAA-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

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      참고문헌 (Reference)

      1 Tillakaratne, N. J., "γ-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues" 112 : 247-263, 1995

      2 Bu, D. F., "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene" 89 : 2115-2119, 1992

      3 Crestani, F., "Trace fear conditioning involves hippocampal α5 GABAA receptors" 99 : 8980-8985, 2002

      4 Gottesmann, C., "The transition from slow-wave sleep to paradoxical sleep: evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep" 20 : 367-387, 1996

      5 Datta, S., "The rat as an experimental model for sleep neurophysiology" 114 : 1239-1244, 2000

      6 Rao, S., "The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia" 13 : 227-235, 2017

      7 Sieghart, W., "Structure and pharmacology of γ-aminobutyric acidA receptor subtypes" 47 : 181-234, 1995

      8 Trachsel, L., "Sleep continuity and the REM-nonREM cycle in the rat under baseline conditions and after sleep deprivation" 49 : 575-580, 1991

      9 McKernan, R. M., "Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor α1 subtype" 3 : 587-592, 2000

      10 Ma, Y., "Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems" 30 : 1748-1753, 2007

      1 Tillakaratne, N. J., "γ-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues" 112 : 247-263, 1995

      2 Bu, D. F., "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene" 89 : 2115-2119, 1992

      3 Crestani, F., "Trace fear conditioning involves hippocampal α5 GABAA receptors" 99 : 8980-8985, 2002

      4 Gottesmann, C., "The transition from slow-wave sleep to paradoxical sleep: evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep" 20 : 367-387, 1996

      5 Datta, S., "The rat as an experimental model for sleep neurophysiology" 114 : 1239-1244, 2000

      6 Rao, S., "The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia" 13 : 227-235, 2017

      7 Sieghart, W., "Structure and pharmacology of γ-aminobutyric acidA receptor subtypes" 47 : 181-234, 1995

      8 Trachsel, L., "Sleep continuity and the REM-nonREM cycle in the rat under baseline conditions and after sleep deprivation" 49 : 575-580, 1991

      9 McKernan, R. M., "Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor α1 subtype" 3 : 587-592, 2000

      10 Ma, Y., "Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems" 30 : 1748-1753, 2007

      11 McCarley, R. W., "Neurobiology of REM and NREM sleep" 8 : 302-330, 2007

      12 Bao, G. H., "Morphinane alkaloids with cell protective effects from Sinomenium acutum" 68 : 1128-1130, 2005

      13 Jin, H. Z., "Morphinane alkaloid dimers from Sinomenium acutum" 71 : 127-129, 2008

      14 Crestani, F., "Molecular targets for the myorelaxant action of diazepam" 59 : 442-445, 2001

      15 Low, K., "Molecular and neuronal substrate for the selective attenuation of anxiety" 290 : 131-134, 2000

      16 Seifi, M., "Molecular and functional diversity of GABA-A receptors in the enteric nervous system of the mouse colon" 34 : 10361-10378, 2014

      17 Zhenzhen Hu, "Methanol Extract of Zizyphi Spinosi Semen Augments Pentobarbital-Induced Sleep through the Modification of GABAergic Systems" 한국생약학회 18 (18): 67-75, 2012

      18 Yuan Ma, "Methanol Extract of Longanae Arillus Regulates Sleep Architecture and EEG Power Spectra in Restraint-Stressed Rats" 한국생약학회 15 (15): 213-221, 2009

      19 Abourashed, E. A., "In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors" 11 : 633-638, 2004

      20 Morton, G. J., "Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice" 300 : E392-E401, 2011

      21 Chung-Soo Kim, "Herbs for the Treatment of Insomnia" 한국응용약물학회 19 (19): 274-281, 2011

      22 Macdonald, R. L., "GABAA receptor channels" 17 : 569-602, 1994

      23 Rudolph, U., "GABA-based therapeutic approaches:GABAA receptor subtype functions" 6 : 18-23, 2006

      24 Collinson, N., "Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor" 22 : 5572-5580, 2002

      25 Sanford, L. D., "Effects of tetrodotoxin (TTX) inactivation of the central nucleus of the amygdala (CNA) on dark period sleep and activity" 1084 : 80-88, 2006

      26 Tokunaga, S., "Effect of valerian extract preparation (BIM) on the sleep-wake cycle in rats" 30 : 363-366, 2007

      27 Han, S., "Effect of hydroxyl and amino groups on electrochemiluminescence activity of tertiary amines at low tris(2,2’-bipyridyl)ruthenium(II) concentrations" 81 : 44-47, 2010

      28 Chen, Y. -J., "Effect of Cordyceps sinensis on the proliferation and differentiation of human leukemic U937 cells" 60 : 2349-2359, 1997

      29 Wagner, C., "Comparative study of quercetin and its two glycoside derivatives quercitrin and rutin against methylmercury (MeHg)-induced ROS production in rat brain slices" 84 : 89-97, 2010

      30 Siegel, J. M., "Clues to the functions of mammalian sleep" 437 : 1264-1271, 2005

      31 Wang, W., "Chloride homeostasis differentially affects GABAA receptor- and glycine receptor-mediated effects on spontaneous circuit activity in hippocampal cell culture" 406 : 11-16, 2006

      32 Paxinos, G., "Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight" 13 : 139-143, 1985

      33 Rudolph, U., "Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes" 401 : 796-800, 1999

      34 Wolfman, C., "Anxioselective properties of 6,3’-dinitroflavone, a high-affinity benzodiazepine receptor ligand" 318 : 23-30, 1996

      35 Zhu, Q., "Antinociceptive effects of sinomenine in a rat model of neuropathic pain" 4 : 7270-, 2014

      36 Li, S. P., "A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury" 73 : 2503-2513, 2003

      37 West, M. R., "A microplate assay measuring chloride ion channel activity" 241 : 51-58, 1996

      38 Wang, X., "8-demethoxyrunanine from Sinomenium acutum" 78 : 593-595, 2007

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