• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• 동의생리병리학회지
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• 제34권2호
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• pp.88-96
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• 2020

Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) are herbal extracts widely used in food and traditional herbal medicine, and have the ability to perform a wide range of biological activities. We aimed to investigate the effects of the SH and VB combination (SHVB) on mice models of chronic restraint stress (CRS) and pentobarbital-induced sleeping behaviors to elucidate its possible mechanisms of action. CRS-exposed mice treated with SHVB showed significantly decreased immobility time, increased swimming and climbing times in the forced swim test (FST), and increased locomotor activity in the open field test (OFT). SHVB decreased serum CORT levels, but enhanced brain monoamine neurotransmitters. SHVB significantly decreased the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behavior in mice. SHVB showed inhibitory effect on 5-HT_2A receptor-mediated ERK1/2 phosphorylation. These results suggest that SHVB has antidepressant and hypnotic effects by regulating the 5-HT_2A receptor.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• 동의생리병리학회지
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• 제24권5호
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• pp.770-778
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• 2010

To establish the fundament for EBM of Traditional Korean Medicine, the papers on Pyeongwi-san (Pingwei-san) frequently used in medical institutions of Traditional Korean Medicine were analyzed through researching domestic and international papers. The papers were classified by the registration of domestic or international journals, the year of publishment, experimental fields and the kinds of studies on biological activities. Of total 518 papers on Pyeongwi-san (Pingwei-san), 32 volumes were selected according to selection creteria. 20 volumes were published in domestic journals, 11 in Chinese journal and 1 in Japanese journal. The papers on instrumental analyses reported the quantification of standard compounds of herbal medicines in Pyeongwi-san (Pingwei-san) using HPLC, GC-MS. The papers on biological activities of Pyeongwi-san (Pingwei-san) showed improvement of gastrointestinal activity and water-electrolyte metabolism, immune regulation, anti-oxidant, anti-inflammatory, analgesic, anti-convulsant activities, hypnotic duration, blood pressure regulation, hepatic protection, congestive heart failure, anti-cancer activities. Further studies including gastrointestinal activity need to be preceeded to establish the fundament for EBM of Pyeongwi-san (Pingwei-san).

• 대한약리학회지
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• 제19권1호
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• pp.77-84
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• 1983

The behavioral pattern of an animal is influenced by endogenous and endogenous stimuli such as humoral secretion, neurohumoral transmitters, drugs, light and environmental change. It has teen known that adenosine is a normal constituent of brain, and has sedative or hypnotic effects and anticonvulsant effects, inhibiting the spontaneous firing of cells in the brain via membrane adenosine receptors. Recent studies suggest that the excitatory responses to xanthines in the CNS might be related to the competitive antagonism of xanthines to adenosine. This study was undertaken to Investigate the effects of adenosine and the CNS stimulants such as picrotoxin, strychnine and caffeine on the spontaneous activity of mire, and to examine the influence of adenosine on the seizures induced by large doses of CNS stimulants. Subjects were $20{\sim}30\;g$ adult mice, and the spontaneous activity was measured using the Selective Activity Meter after intraperitoneal injection of adenosine (10 mg/kg), caffeine (100 mg/kg), strychnine(0.2 mg/kg) or picrotoxin(0.5 mg/kg) with or without adenosine pretreatment. The seizures were induced with caffeine(200, 250 and 300 mg/kg), strychnine(1.25 and 1.5 mg/kg) or picrotoxin(10 and 15 mg/kg). The results are summarized as follows : 1) The spontaneous activity in mite was significantly inhibited between 10 and 20 minutes after adenosine treatment. 2) Caffeine and picrotoxin increased the motor activity significantly while strychnine had no effect on the activity. 3) The ambulatory activity in the caffeine, strychnine and picrotoxin treated groups was significantly inhibited by adenosine pretreatment. 4) The seizures were observed with caffeine(200, 250 and 300 m9/kg), strychnine(1.25 and 1.5 mg/kg) or picrotoxin(10 and 15 mg/kg). The caffeine induced seizures were inhibited by adenosine pretreatment, but the strychnine or picrotoxin induced seizures were not affected.

• Natural Product Sciences
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• 제19권2호
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• pp.179-185
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• 2013

Polygalae radix (PR) has traditionally been used as a sedative and anti-stress agent in oriental countries for a long time. PR which contains many ingredients is especially rich in saponins. This study was performed to investigate whether ethanol extract of PR enhances pentobarbital-induced sleep behaviors. In addition, possible mechanisms also were investigated. PR inhibited locomotor activity in mice. PR increased sleep rate and sleep time by concomitant administration with sub-hypnotic dose of pentobarbital (28 mg/kg). PR prolonged total sleeping time, and shortened sleep latency induced by pentobarbital (42 mg/kg). In addition, PR increased intracellular chloride concentration in primary cultured neuronal cells. The expression level of glutamic acid decarboxylase (GAD) were increased, and ${\gamma}$-aminobutyric acid $(GABA)_A$ receptors subunits were modulated by PR, especially increasing ${\gamma}$-subunit expression. In conclusion, PR augments penobarbital-induced sleep behaviors through activation of $GABA_A$ receptors and chloride channel complex.

• Natural Product Sciences
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• 제5권3호
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• pp.142-147
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• 1999

Tiliacora racemosa Colebr. belonging to the family Menispermaceae is the biggest store-house of diphenyl bisbenzylisoquinoline (DBBI) alkaloids. Exhaustive chemical processing of the root of T. racemosa by the application of modern separation techniques yielded a DBBI alkaloid which was identified as tiliacorine using sophisticated spectroscopic methods (UV, IR, $1^H-NMR$, Mass). Tiliacorine potentiated the sleeping time induced by standard hypnotics viz. chlorpromazine (CPZ), pentobarbitone (PB) and diazepam (DZ) in a dose dependent manner. Tiliacorine potentiated the analgesic action of standard analgesic agents viz., morphine and meperidine. It was also found to possess anti convulsive activity in the strychnine induced convulsion model.

• Natural Product Sciences
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• 제18권2호
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• pp.67-75
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• 2012

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.

• 생명과학회지
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• 제16권1호
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• pp.156-161
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• 2006

The essential oil of Nardostachys jatamansi (Valerianaceae), which has been used for a long time in aroma therapy, was investigated after inhalation or oral administration for its analgesic effect, anticonvulsant action, hypnotic effect and in vitro inhibitory activity on monoamine oxidase. This fragrance oil showed a significant analgesic effect in the phenylquinone-induced .writhing test, suppressed the convulsion induced by pentylenetetrazole and lengthened the pentobarbital-induced sleeping time in a time-dependent manner after fragrance inhalation or dose-independently by oral administration. Its inhibitory activity on monoamine oxidase was remarkable, showing $49.4\%$ inhibition at a concentration of 5.0 mg/ml. Six new terpenes with seven known compounds were detected by our GC-MS analytical conditions used. As a result, the essential oil fragrance of Nardostachys jatamansi would be clinically useful for a sedative by either inhalation or oral administration.

• 생물정신의학
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• 제4권1호
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• pp.54-59
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• 1997

Objects : Sanjoin, the seeds of Zizyphus vulgaris var. spinosus has been used as the most important hypnotic agent in chinese medicine to treat insomnia. This research was performed in order to examine the effect of betulinic acid and sanjoinine-A which are components of Sanjoin. Method : Sleeping time, sleep recordings of EEG, EMG, serum serotonin level, and locomotor activity were measured in rats which received betulinic acid and sanjoinine-A as sleep induction material extracted from Sanjoin. Results : 1) Groups received betulinic acid, sanjoinine-A, and lorazepam showed increased sleep time than control group with saline. 2) Groups with betulinic acid, sanjoinine-A, lorazepam and saline recorded ${\beta}$-wave in sleep recordings of EEG. In EMG, there was no significant difference among all groups. 3) No significant difference in serum serotonin level among all groups was found. 4) In autonomic activity testing, groups of betulinic acid, sanjoinine-A, and lorazepam showed significantly more decreased in activity than saline group. In comparison of groups of betulinic acid and sanjoinine-A with a group of lorazepam, there was no significant difference. Conclusion : These results suggest that betulinic acid and sanjoinine-A have the sedative effect like lorazepam rather than sleep effect.