• Archives of Pharmacal Research
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• 제19권6호
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• pp.480-485
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• 1996

Brain GABA transaminase is inactivated by preincubation with antidepressant/antipanic drug pheneizine (${\beta}$ethylphenylhydrazine) (mixing molar ratio 10:1) at pH 7.4. The reaction of enzyme with phenelzine was monitored by absorption and fluorescence spectroscopic methods. The inactive enzyme was fully reconstituted by addition of cofactor pyridoxal-5-phosphate. This result implies that the blocking of 1 mol of pyridoxal-5-phosphate per enzyme dimer is needed for inactivation of the enzyme. The time course of the reaction is significantly affected by the substrate .alpha.-ketoglutarate, which afforded complete protection against the loss of catalytic activity. The kinetic studies shows that phenelzine reacts with the cofactor of enzyme with a second-order rate constant of $2.1{\times}10^3M^{-1}s^{-1}$. It is postulated that the antidepressant/antipanic drug phenelzine is able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on GABA degradative enzyme GABA transaminase.

• Biomolecules & Therapeutics
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• 제15권1호
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• pp.27-33
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• 2007

The psychopharmacological profile of ginsenosides has not yet been confirmed systematically although various neuropharmacological activities associated with them have been investigated. In the present study, the psychological activities of Rb1 were investigated to evaluate whether it can be used in treatment or prevention of psychological disorders. Rb1 was intravenously injected at doses of O.2,2,5 and 10 mg/kg. The effects of Rb1 on the $Cl^-$ ion influx were investigated using IMR-32 human neuroblastoma cells. Moreover, locomotor activity, forced swimming activity, activity on rotating rod and activity in elevated plus-maze were tested in mice. Rb1 increased the $Cl^-$ influx into the intracell region in a dose-dependent manner. Rb1 did not cause change in behavior in total open field when locomotor activity was tested, however it increased activities, especially, such as rearing frequency in center area. Administration of Rb1 at 0.2 mg/kg significantly reduced activities on rotating rod however administration at high dosages had no effect on them. Rb1 administration decreased animal immobile time in a water chamber in a dose dependent manner, and increased the strong mobile time of animals. In conclusion, the present results demonstrate that Rb1 contributes to the psychopharmacological effects of ginseng and may be used in treatment or prevention of psychological disorders such as anxiety or depression.

• Korean Journal of Acupuncture
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• 제38권3호
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• pp.162-174
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• 2021

Objectives : We aimed to identify the antidepressant effect of liver tonification acupuncture treatment (ACU (LT); KI10, LR8, LU8, LR4) and four gate acupuncture treatment (ACU (FG); LI4, LR3) and its brain neural activity in the normal and chronic restraint stress (CRS)-induced mouse model. Methods : Firstly, normal mice were given ACU (LT) or ACU (FG) and the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Secondly, CRS was administered to mice for 4 weeks, then ACU (LT) or ACU (FG) was performed for 2 weeks. The depression-like behavior was evaluated using open field test (OFT) before and after acupuncture treatment. Then, the c-Fos expressions in each brain region were analyzed to examine brain neural activity. Results : In normal mice, ACU (FG) regulated brain neural activities in the hypothalamus, hippocampus, and periaqueductal gray. ACU (LT) changed more brain regions in the prefrontal cortex, insular cortex, striatum, and hippocampus, including those altered by ACU (FG). In CRS-induced model, ACU (LT) alleviated depression-like behavior more than ACU (FG). Also, brain neural activities in the motor cortex area 2 (M2), agranular ventral part and piriform of insular cortex (AIV and Pir), and cornu ammonis (CA) 1 and CA3 of hippocampus were changed by ACU (LT), and those of AIV and CA3 were also changed by ACU (FG). As in normal mice, ACU (LT) resulted in changes in more brain regions, including those altered by ACU (FG) in CRS model. M2, Pir, and CA1 were only changed by ACU (LT) in depression model, suggesting that these brain regions reflect the specific effect of ACU (LT). Conclusions : ACU (LT) relieved depression-like behavior more than ACU (FG), and this acupuncture effect was associated with modulation of brain neural activities in the motor cortex, insular cortex, and hippocampus.

• Journal of Ginseng Research
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• 제46권5호
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• pp.666-674
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• 2022

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

• Natural Product Sciences
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• 제19권1호
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• pp.8-14
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• 2013

The inhibitory effect and the structure-activity relationships of luteolin and its related derivatives isolated from Taraxacum mongolicum against MAO activities were investigated. The activity-guided isolation of extract from Taraxacum mongolicum led to the isolation of three flavonoids, luteolin, diosmetin, and luteolin-7-glucoside, a polyphenol, chlorogenic acid, a tyrosine and a uridine. The inhibitory activities of luteolin and its related derivatives against MAOs activities are dependent on their molecular structures. The presence of the phenolic hydroxy group at para-position is the active site for MAO-A inhibition as well as of MAO-B. The methoxy group has no potential on MAO-A inhibition. An additional phenolic hydroxy group at the ortho-position alleviates about 4-fold MAO-A inhibitory activity of phenolic hydroxy group at para-position. A carboxylic group seems to be critical for DBH inhibition and has no effects on MAO.

• 한국산학기술학회논문지
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• 제15권11호
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• pp.6739-6745
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• 2014

은행속에 속하는 산청목은 중국과 한국 북동부지역에 널리 분포하는 자생 식물로 전통적으로 항염증제로 사용되었으며 현재까지 항우울에 대한 효능과 그에 대한 면역변화에 대한 연구는 미흡한 실정이다. 본 연구실에서는 100, 200, 그리고 400 mg/kg 농도의 산청목추출물을 실험쥐에게 경구투여를 실행하였으며 강제수영실험을 통하여 항우울효과를 평가 그리고 혈 중 코티솔, ACTH, 그리고 사이토카인의 농도를 측정하였다. 실험 결과 실험쥐에 경구투여한 산청목 투입량이 증가함에 따라 강제수영실험에서의 행동불능시간이 감소하였으며 수중공포에 의해 분비유도된 사이토카인 농도 또한 감소함을 볼 수 있었다. 특히 코티솔, IL-6 과 $IL-1{\beta}$농도가 산청목 투입군에서 유의하게 감소함을 알 수 있었다. 산청목 경구투여군에서의 부동시간의 감소와 전염증성 사이토카인의 저하를 종합하여 볼 때 산청목의 항염증 효능으로 인한 작용에 의하여 강제수영 실험에서 항우울효과가 발현했다고 간주된다.

• 동의신경정신과학회지
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• 제12궈1호
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• pp.123-135
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• 2001

Objective: This study was designed to assess antidepressant effects of Quibitang on an Animal Model of Depression induced by Chronic Mild Stress. Method: The consumption of 1% sucrose solution and active avoidance learning test were used to evaluate antidepressant effect of Quibitang. The consumption of 1% sucrose solution was measured every week for 8 weeks, and active avoidance learning test was executed after 4 weeks treatment of saline or Quibitang. Result: 1. The consumption of 1% sucrose solution was significantly reversed in test group (Quibitang-treated group) at 5th, 7th, 8th weeks, but there was no significant change in control group. 2. Chronic Mild Stress was found to suppress the increase of body weight at 5th, 6th, 7th, 8th weeks. Treatment of Quibitang did not enhanced the body weigt, but it enhanced the consumption of sucrose solution. 3. In order to measure the learning ability of rat which drived to be depressed, we executed active avoidance test. The result revealed that depressed rat showed impaired acquisition than control group, and the treatment of Quibitang restored the learning activity. Conclusion: These results suggest that Quibitang may have antidepressant effects on depression induced by chronic mild stress.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.79-83
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• 2013

The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

• 대한본초학회지
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• 제26권2호
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.114-118
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• 2006

Depression is a very difficult disease to be cured because several nervous systems are involved. In the present study, we evaluated the effects of Keum-Ryung-Ja-San (KRJS), a traditional herbal prescription, on depressive behaviors in mice using the forced swimming test. KRJS was given 1 h prior to the forced swimming test (50, 100, 200, an400 mg/kg, p.o.). The duration of immobility time in the forced swimming test was significantly reduced by KRJS treatment (200 mg/kg, P<0.05) and similar effects were observed with a classical antidepressant, imipramine (15 mg/kg, i.p.). With subchronic administrations of KRJS and its constituents at several doses for 1 week, a decreased duration of immobility time was observed with KRJS and Corydalis ternata (200 mg/kg, p.o. P<0.05). These results suggest that KRJS may have antidedpressive activities and CT may contribute to the antidepressive activity of KRJS.