• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.195-211
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• 2002

Gagamguibitang, a composite Korean medicinal drug prescribed by us, was evaluated for its sedative effects by measurements of potentiation on pentobarbital-induced sleeping time, anticonvulsive activities in animal model, inhibitory effect on GABA transaminase activity, and antioxidative activities in vitro- and/or in vivo assay. The results were summerized as follows : 1. Gagamguibitang showed about 2-fold prolongation of pentobarbital-induced sleeping time compared to the control group after administration(p.o) with 2.0g/kg of mice body weight. 2. Gagamguibitang strongly lengthened onset time of pentylenetetrazole-induced convulsion, shortened the duration of convulsion and diminished the lethality after treatment(p.o) with 1.0g/kg of mice body weight. 3. Gagamguibitang inhibited dose-dependently the brain GABA transaminase activity in vitro compared to the control group and in vivo compared to the pentylenetetrazole-treated group. 4. Gagamguibitang inhibited effectively brain lipid peroxidation by 45.8% at a dose of l0mg/ml in vitro and by 47.5% after oral treatment with 0.5g/kg of mice body weight in vivo assay. 5. Gagamguibitang exhibited a potent scavenging activity on DPPH radical in a dose-dependent manner with ca. 92% activity at l0mg/ml. As a result, Gagamguibitang can be useful for the effective sedative drug in clinical application.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.201-208
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• 2017

Background: Panax vietnamensis Ha et Grushv. or Vietnamese ginseng (VG) is a recently discovered ginseng species. Studies on its chemical constituents have shown that VG is remarkably rich in ginseng saponins, particularly ocotillol saponins. However, the psychopharmacological effects of VG have not been characterized. Thus, in the present study we screened the psychopharmacological activities of VG in mice. Methods: VG extract (VGE) was orally administered to mice at various dosages to evaluate its psychomotor (open-field and rota-rod tests), sedative-hypnotic (pentobarbital-induced sleeping test), anti-stress (cold swimming test), anxiolytic (elevated plus-maze test), and cognitive (Y-maze and passive-avoidance tests) effects. Results: VGE treatment increased the spontaneous locomotor activity, enhanced the endurance to stress, reduced the anxiety-like behavior, and ameliorated the scopolamine-induced memory impairments in mice. In addition, VGE treatment did not alter the motor balance and coordination of mice and did not potentiate pentobarbital-induced sleep, indicating that VGE has no sedative-hypnotic effects. The effects of VGE were comparable to those of the Korean Red Ginseng extract. Conclusion: VG, like other ginseng products, has significant and potentially useful psychopharmacological effects. This includes, but is not limited to, psychomotor stimulation, anxiolytic, antistress, and memory enhancing effects.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.614-619
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• 2011

Nelumbo nucifera(NN) is a oriental medicinal herb which has been used traditionally for the treatment of antidiarrhea, sedative action and various brain diseases including convulsion and epilepsy. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of NN(100, 200 mg/kg, P.0) to the sleeping time and pentylenetetrazole(PTZ)-induced convulsive mice. The methanol extract of NN prolonged sleep time by pentobarbital. Methanol extracts of NN were not effected the concentration of GABA and GABA-T activity in the brain of PTZ-induced mice. Methanol extracts of NN significantly inhibited the convulsion state as well as the level of lipid peroxidation in the brain. The butanol and dichloromethane fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently($5.0{\times}10^{-6}\sim2.0{\times}10^{-5}\;g/ml$). These results suggest that the anticonvulsive effect of NN is possibly due to the antioxidative effects of the free radical formation at brain for the PTZ-induced convulsion if it were by due to generating system.

• Journal of Life Science
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• v.32 no.8
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• pp.601-610
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• 2022

P. tenebrifer (PT) belongs to the Diptera order and Stratiomyidae family. Recently, insect industry have been focused as food, animal feed and environmental advantages. γ-aminobutyric acid (GABA) and melatonin have been associated with regulating sleep and depression. GABA is the primary inhibitory neurotransmitter and is synthesized via biotransformation of monosodium glutamate (MSG) to GABA by lactic acid bacteria. In this study, we first used a GABA-enhanced PT extract, wherein GABA was enhanced by feeding MSG to PT. The underlying mechanisms preventing stress and insomnia were investigated in a corticosterone (CORT)-induced endoplasmic reticulum (ER) stress and chronic restraint stress (CRS)-exposed mouse model, as well as in pentobarbital (45 mg/kg)-induced sleep behaviors in mice. In the present study, the GABA peak was detected in high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) analysis and showed in Ptecticus tenebrifer water extract (PTW) but not in non-PTW extract. The results showed that PTW and Ptecticus tenebrifer with 70% ethanol extract (PTE) exerted neuroprotective effects by protecting against CORT-induced downregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP-response element binding protein (CREB) expression. In addition, PTW (300 mg/kg) significantly reduced CORT levels in CRS-exposed mice. Furthermore, PTW (100 and 300 mg/kg) significantly reduced sleep latency and increased total sleep duration in pentobarbital (45 mg/kg)-induced sleeping behaviors, which was related to serum melatonin levels. In conclusion, our results suggest that PTW exerts anti-stress and sleep-enhancing effects by regulating serum CORT and melatonin levels.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.233-248
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• 1998

This study was conducted to investigate effects of Dansambohyultang on serum gastrin, secretin release and CNS in rats and mice. One group of seven rats was intactly in normal condition, the other group of seven rats was respectively heated, starved, and stressfully immobilized. The third group of seven rats was provided with Dansambohyultang before the stress, and the forth one after the stress. And, gastrin concentration and secretin concentration were measured. Mice were studied with regard to convulsion time, total sleep time and analegic effects on cental nerve system. The results were as follows: 1. Gastrin concentration was significantly decreased, and secretin concentration was significantly increased. 2. Analegic effect by acetic acid method was recognizably observed. 3. Effect of total sleep time done by pentobarbital-Na was recognizably observed. 4. Anti-convulsion effects induced by strychnine, picrotoxin and caffeine were recognizable. It is inferred from above results that Dansambohyultang inhibits gastin release, stimulates secretin release and palliate the pain.

• The Journal of Korean Medicine
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• v.15 no.2 s.28
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• pp.184-197
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• 1994

In order to investigate the effects of Kamikwakjeongtang by using the experimental animals. the action on gastrointestinal smooth muscles. the action of gastric juice secretion, the action of antiulcer. the transport ability of intestinal contents. the action of anticatharsis and the actions on the central nervous system were studied. The results were as follow: 1. Spontaneous motility of the isolated ileum of mice was suppressed and antiacetylcho-line chloride action was recognized. 2. Anti-action on barium chloride of fundus-strip of white rat was recognized. 3. Supression effects on gastric juice secretion. free acidity was recognized. 4. Preventive effect on the ulcer induced by pylorus-ligated was recognized. 5. Supression effects of large intestinal transport ability was recognized. 6. Anti-carthartic action was shown but was not recognized. 7. Analgesic effect by the acetic-acid method and prolonged effect of the total sleep time by pentobarbital-Na were recognized. According to the above results, effects based on oriental medical reference were consistent with the actual experimental effects.

• Korean Journal of Plant Resources
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• v.26 no.1
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• pp.44-51
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• 2013

Morinda officinalis (MO) is a oriental medicinal herb which has been used traditionally for the treatment of impotence, anti-inflammatory, menstrual irregularity action and various brain diseases including antidepressant and anti-stress. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of MO (100, 200 mg/kg, P.0) to the sleeping time and pentylenetetrazol (PTZ)-induced convulsive mice. The methanol extract of MO prolonged sleep time by pentobarbital. Dose-dependent of methanol extracts of MO were effected the concentration of GABA and GABA-T activity in the brain of PTZ-induced mice. Methanol extracts of MO significantly inhibited the convulsion state as well as the level of lipid peroxidation in the brain. The butanol and dichloromethane fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently ($5.0{\times}10^{-2}{\sim}20.0{\times}10^{-2}g/ml$).

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.101-119
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• 2004

Ginseng Radix Alba and Cyperi Rhizoma were investigated for their anti-depressant effects. For this purpose, forced-swimming test, tail suspension test, hot plate test, reserpine-induced hypothermia, aggressive behavior test were performed. In addition, the brain content of 5-hydroxyindoleacetic acid(a metabolite of serotonin), the monoamine oxidase activity, anticonvulsant effect, sleep enhancement effect were determined. The results are as follows: In the forced swimming test, Ginseng Radix diminished the duration of immobility by 45.5% compared to the control group, while Cyperi Rhizoma showed weaker effect (12.4% reduction) at 2g/kg. In the tail suspension test, the effect of Ginseng Radix(43.7% reduction) are also better than that of Cyperi Rhizoma(15.6% reduction) at 2g/kg. In the hot plate test, Ginseng Radix showed no difference as compared to control, while Cyperi Rhizoma increased the jump latency time by about 25% after administration for 10 days. In the reserpine-induced hypothermia test, both drugs slowly dropped the body temperature compared to the control group, especially the rate of hypothermia of Ginseng Radix was 24.0% at 1g/kg. In the aggressive behavior test, both drugs delayed the onset time, decreased the duration and frequency, of which effects were better in Cyperi Rhizoma. The content of 5-hydroxyindoleacetic acid in mice brain was slightly increased in Ginseng Radix, while Cyperi Rhizoma increased its level almost to the control group. Both drugs inhibited the monoamine oxidase activity in a dose-dependent manner, but the effect(51.2%) of Cyperi Rhizoma was more potent than the effect(11.8%) of Ginseng Radix. In the pentobarbital-induced sleep test, Cyperi Rhizoma exhibited no significant difference against the control group, while Ginseng Radix showed about two-fold enhancement at 2g/kg. The anticonvulsant effect of both drugs delayed the onset time, shortened the duration of convulsion and diminished the lethality, but Ginseng Radix were better than Cyperi Rhizoma.

• Natural Product Sciences
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• v.18 no.4
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• pp.215-220
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• 2012

The stem of Lindera obtusiloba (Lauraceae), has been widely used as a traditional medicine for the treatment of abdominal pain, bruise and hepatocirrhosis. In the present study, antinociceptive and sedative properties of the methanol extract of L. obtusiloba (MLO) were evaluated. MLO demonstrated strong and dose-dependent antinociceptive activities on various experimental pain models including thermal nociception and chemical nociception, compared to tramadol and indomethacin, reference drugs. In combination test using naloxone, the diminished analgesic activity of MLO was observed, indicating the relation with opioid receptor. Moreover, MLO also decreases pentobarbital-induced sleep latency and increases sleeping time suggesting its hypnotic and sedative action. The present results indicate that MLO could be used as valuable antinociceptive and sedative agent for the treatment of various diseases.