• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.25-33
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• 1999

Benzodiazepines(BZDs) are among the most widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the $GABA_A$/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.

• Animal cells and systems
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• v.1 no.3
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• pp.467-473
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• 1997

Taurine (2-aminoethanesulfonic acid), one of bioactive amino acid in the mammalian brain, is known to exert inhibitory effects on neurons via GABA receptor. In the present study, we examined effects of taurine on glutamateinduced neurotoxicity on hippocampal neuron cell culture using cell counting method and lactate dehydrogenase (LDH) assay. After 10 d of culture, cells were stimulated with appropriate drugs. Only 43% of cultured neuronal cells survived at one day after stimulation with 500 uM L-glutamate for 10 min. Survival rate was enhanced by 82% in the presence of 10 mM taurine. LDH activity from the culture supernatant incubated with a combination of L-glutamate and taurine was less than half of that with L-glutamate alone. In the next series of experiments, interleukin-6 (IL-6) mRNA expression in cultured astrocytes was investigated using reverse tanscription-PCR (RT-PCR). IL-6 mRNA was detected in the astrocytes stimulated with L-glutamate in a dose-dependent manner, while not detected in the unstimulated control astrocytes. The expression of IL-6 mRNA caused by 10 mM glutamate was inhibited by taurine, but not by GABA. These findings demonstrated a neuroprotective action of taurine against glutamate-induced toxicity.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.213-218
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• 2011

The aim of this study is to evaluate the sedative effects of ethanol extract and the three major constituents of Cimicifugae Rhizoma. They decreased locomotor activity significantly, and enhanced sleeping duration induced by thiopental sodium. The ethanol extract of Cimicifugae rhizoma and 24-epi-7,8-didehydrocimigenol-3-xyloside (24-epi.) increased the $Cl^-$ influx into the intracellular area of SH-SY5Y neuroblastoma cells significantly. The present results demonstrate that the sedative effects of Cimicifugae rhizoma are mediated via the GABA-gated $Cl^-$ channel, partly by 24-epi.

• Journal of Acupuncture Research
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• v.17 no.4
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• pp.5-17
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• 2000

To research the characteristics of ion currents induced by Bujaijung-tang and Bojungikgi-tang, nystatin-perforated patch clamp technique under voltage-c(amp condition was used. Periaqueductal gray neuron was dissociated from Sprauge-Dawley rat, 10-15 days old. Cytotoxicity of Bujaijung-tang and Bojungikgi-tang showed incubation time and concentration dependent manner. Ion current activated by Bujaijung-tang and Bojungikgi-tang were inhibited by bicuculline and strychnine and CNQX. It can be suggested that Bujaijung-tang and Bojungikgi-tang modulate inhibitory and excitatory neurotransmitters-, GABA, glycine and non-NMDA, acticvated ion channels. Modulatory effect of Bujaijung-tang and Bojungikgi-tang was more greater in inhibitory neurotransmitters. Low concentration of Bujaijung-tang which dose not elicit ion current itself, activated GABA and glycine induced chloride currents. In this study, we can found that the activation of Bujaijung-tang and Bojungikgi-tang on non-NMDA subtypes of glutamate receptor is its major action mechanism and can be used as very effective Herb treatment on Myasthenia gravis patient.

• Natural Product Sciences
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• v.15 no.3
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• pp.115-120
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• 2009

Woohwangcheongsimwon (WHCSW) is a traditional oriental medicinal fomula which has been clinically used for treating strokes, palpitation, loss of consciousness and anxiety. The purpose of this study was to characterize the putative anxiolytic properties of WHCSW using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). In the EPM test, WHCSW significantly increased the percentage of time-spent in the open arms (200 mg/kg, P < 0.05) and the percentage of open arm entries (200 and 400 mg/kg, P < 0.05). WHCSW also significantly increased the number of head-dips in the hole-board test (200 mg/kg, P < 0.05). In addition, the anxiolytic properties of WHCSW examined in the EPM test were inhibited by flumazenil (10 mg/kg, i.p.), a GABA$_A$ antagonist. However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus 10% Tween 80 controls. These results suggested that WHCSW is an effective anxiolytic agent, and that its anxiolytic effects are mediated via GABA$_A$ receptors.

• Journal of Ginseng Research
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• v.36 no.4
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• pp.403-410
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• 2012

The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented ${\alpha}$-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The ${\alpha}$-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both ${\alpha}$- and ${\beta}$-subunits of the ${\gamma}$-aminobutyric acid $(GABA)_A$ receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via $GABA_A$ergic systems.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.255-262
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• 2005

Striatum is involved in the control of movement and habitual memory. It receives glutamatergic input from wide area of the cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from the raphe nuclei. In our study, the effects of 5-HT on synaptic transmission were studied in the rat corticostriatal brain slice using in vitro whole-cell recording technique. 5-HT inhibited the amplitude as well as frequency of spontaneous excitatory postsynaptic currents (sEPSC) significantly, and neither ${\gamma}-aminobutyric$ acid (GABA)A receptor antagonist bicuculline (BIC), nor $N-methyl-_{D}-aspartate$ (NMDA) receptor antagonist, $_{DL}-2-amino-5-phosphonovaleric$ acid (AP-V) could block the effect of 5-HT. In the presence non-NMDA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenxo[f] quinoxaline-7-sulfonamide (NBQX), the inhibitory effect of 5-HT was blocked. We also figured out that 5-HT change the channel kinetics of the sEPSC. There was a significant increase in the rise time during the 5-HT application. Our results suggest that 5-HT has an effect on both pre- and postsynaptic site with decreasing neurotransmitter release probability of glutamate and decreasing the sensitivity to glutamate by increasing the rise time of non-NMDA receptor mediated synaptic transmission in the corticostriatal synapses.

• 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 Life Science
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• v.29 no.5
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• pp.564-569
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• 2019

Heavy drinking disrupts the nervous system by activation of GABA receptors and inhibition of glutamate receptors, thereby preventing short-term memory formation. Degradation of cognition by alcohol induces blackouts, and it can lead to alcoholic dementia if repeated. Therefore, drugs need to be developed to prevent alcohol-induced blackout. In this study, we confirmed the effect of an ethanol extract of Cassia obtusifolia seeds (COE) on alcohol-induced memory impairment. The effects of COE and ethanol on cognitive functions mice were examined using the passive avoidance and Y-maze tests. The manner in which alcohol affects long-term potentiation (LTP) in relation to the learning and memory was confirmed by electrophysiology performed on mouse hippocampal slices. We also measured N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory synapses (fEPSPs), which have a known association with cognitive impairment caused by ethanol. Ethanol caused memory impairments in passive avoidance and Y-maze tests. COE prevented these ethanol-induced memory impairments in these tests. Ethanol also blocked LTP induction in the mouse hippocampus, and COE prevented this ethanol-induced LTP deficit. Ethanol decreased NMDA receptor-mediated fEPSPs in the mouse hippocampus, and this decrease was prevented by COE. These results suggest that COE might be useful in preventing alcohol-induced neurological dysfunctions, including blackouts.

• Natural Product Sciences
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• v.26 no.1
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• pp.1-9
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• 2020

Flavonoids are mainly contained in the vegetables and medicinal herbs. Until now, over 5,000 kinds of flavonoid have been identified and their biological activities have been reported. Among them, we are interested in oroxylin A and spinosin because of their specific structures having bulky group at C-6 of ring A. Oroxylin A is contained in the Scutellaria baicalensis and exhibits cognitive enhancing activity as a GABA_A receptor antagonist, which is different from those of mainly contained in the S. baicalenis, baicalein or wogonin. Spinosin is isolated from Zizyphus jujuba var. spinosa and mainly studied as a hypnotic or anxiolytic agent because of traditional knowledge about its original herb. As far as we know, the cognitive function of spinosin was first identified by our group. In this review, we discuss how such flavonoids exert their pharmacological activities associated with cognitive function based on the receptor binding study and behavioral studies. Traditional knowledge and reverse pharmacology may be addressed in the research field of phytochemical pharmacology and useful to unveil the secret of phytochemicals.