• 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.

• Journal of Oriental Neuropsychiatry
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• v.17 no.3
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• pp.21-43
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• 2006

This study was designed to assess Effects of jingansikpungtanggagam-bang on Central Nerve System. Method : jingansikpungtanggagam-bang, a Korean traditional prescription, was evaluated for its anticonvulsant effect, hypnotic activity, analgesic action, anxiolytic effect, memory enhancement, and MAO inhibitory activity and detennined the content of neurotransmitter in brain by HPLC method. Result : 1. The extract increased potently anticonvulsant effect at 1g/kg by 5.6-fold extention of onset time against control group. 2. The extract increased hvrmsis at 500mg/kg by over twofold length of sleeping time compared to control. 3. The extract showed a significant analgesic effect with 86.0% inhibition on writhing frequency at 500mg/kg by phenylquinone-induced writhing test. 4. The extract inhibited dose-dependently the activity of monoamine oxidase in vitro. 5. This prescription increased the brain levels of serotonin and 5-hydroxyindoleacetic acid by 3.3% and 1.4%, respectively. 6. the extract exhibited the anxiolytic effect with 21.3% decrease of the immobility duration against control group. 7. the extract enhanced memory recovery on scopolamine-induced impairment of passive avoidance performance at 1g/kg pretreatment with 20.2% increase of latency time. Conclusion : The result sugguest that jiugansikpungtanggagam-bang can be used effectively as a sedative prescription in Korean traditional medicine.

• Archives of Pharmacal Research
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• v.11 no.1
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• pp.33-40
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• 1988

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treating t-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate and t-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate with p-toluenesulfonic acid in $CH_3$CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at both in vitro and ex vivo levels. It was found from in vitro measurements that (E)-p-NTCP at $6.0{\times}10^{-5}M$ elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast, (E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with $IC_{50}$ values, $2.5{\times}10^{-7}M\;and\;1.4{\times}10^{-6}M$, respectively. It was also noted from (E)-m-NTCP that m-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According to ex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by (E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas, (E)-m-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between (E)-m-NTCP and (E)-p-NTCP were sought in relation to differing electron withdrawing effects of m- and p-substituents which will influence electron density of the side chain amino functions and the partitions.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.

• Journal of Oriental Neuropsychiatry
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• v.32 no.1
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• pp.25-37
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• 2021

Objectives: Depression is a mood disorder showing low energy, loss of interest, anhedonia, and anxiety. It affects a patients' daily life. This disease is considered a social problem because the patient may commit suicide in extreme cases. JSB is composed of 12 Korean medicinal herbs. It has been prescribed to patients with depression. The objective of this study is to investigate anti-depressive effects of JSB on restraint stress-induced depression in a mouse model. Methods: Depression was induced by restraint stress. Mice were orally administered JSB at 10, 20, or 40 mg/kg for 14 days. Forced swimming test (FST) and open field test (OFT) were performed. Brain-derived neurotrophic factor (BDNF) mRNA level was measured by real time-PCR. Plasma levels of corticosterone and serotonin were measured by ELISA. Blood levels of AST and ALS were measured using a biochemical analyzer. Results: JSB treatment significantly reduced the immobility time in FST. BDNF mRNA level was increased by JSB treatment in the hippocampi of mice. Although the expression of TNF-α was also increased by JSB, such increase was not statistically significant. The increase of corticosterone level in plasma induced by restraint stress was significantly down-regulated by JSB. JSB reduced blood level of AST, but not ALT. Conclusions: JSB has a potential to manage depression, setting a foundation for clinical application of Korean medicine with safety.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.245-250
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• 2015

Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.202-202
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• 1996

The antihistaminic action of eighteen herbal medicines was investigated by the radioligand binding and functional assays. The hexane fractions of Trichosanthis radix, Mori cortex radicis and Evodiae fructus dose-dependently inhibited [$^3$H]mepyramine binding to H$_1$ receptor and histamine-induced contraction in guinea-pig brain homogenates and isolated guinea-pig ilea, respectively. Antihistaminic action of the hexane and ethylacetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus was more potent than their antimuscarinic action evaluated from the inhibition of [$^3$H]QNB binding and carbachol response. The ethylacetate and chloroform fractions and six known flavonoids from Scutellariae radix also inhibited histamine-induced contraction, but antihistaminic potencies of these fractions and compounds were almost identical with their antimuscarinic potencies. The hexane fractions of Mori cortex radicis and Evodiae fructus, as shown in ketotifen, inhibited selectively the increase of cutaneous vascular permeability induced by histamine. However, wogonin (SC-1) from Scutellariae radix was a nonselective inhibitor for the effect of histamine and serotonin on the vascular permeability. These results demonstrate that the hexane and ethylacetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus have the selective histamine H$_1$ receptor blocking activities.

• YAKHAK HOEJI
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• v.53 no.5
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• pp.241-249
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• 2009

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the combination relieving effect of green tea extract(GTE) and L-theanine on the stress induced by electric foot shock. Four week oral administration of GTE (24 mg/kg), L-theanine (4 mg/kg) or their combination reduced the levels of dopamine, noradrenaline and corticosterone in blood, brain cortex, hippocampus, and striatum, wherease increased serotonin level. The combination of GTE and L-theanine showed much greater effects than single treatment of each component, and the effects are comparable to diazepam (2 mg/kg). Therefore, this study suggests that the combination of GTE and L-theanine may act effective and be useful for stress relieving treatment.

• Bulletin of the Korean Chemical Society
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• v.27 no.8
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• pp.1189-1193
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• 2006

In order to develop radiopharmaceuticals for targeting a serotonin receptor such as $5-HT_{1A}$, histidine-$C_n$-arylpiperazines (AP) (C = alkyl, n = 2, 3, 4) were prepared in five steps with yields of 25%, 37% and 51%, respectively, and radiolabeled with the $[^{99m}Tc(CO)_3(H_2O)+3]^+$. The $^{99m}Tc(CO)_3$-Histidine-Cn-APs were prepared with a high yield (>99%) and characterized as a tridentate complex with a neutral charge to pass through the blood-brain barrier (BBB). The rhenium complexes with $Re(CO)_3$ were also synthesised and comparative experiments were achieved to evaluate the nature of the $^{99m}Tc$ complexes.

• Sleep Medicine and Psychophysiology
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• v.2 no.2
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• pp.133-137
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• 1995

The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.