• 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.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.22-37
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• 2001

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.

• 대한본초학회지
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• 제25권2호
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• pp.117-128
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• 2010

Objectives : In this study the antidepressant effects of mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex on the change of HPA-Axis and Catecholamic system was investigated Methods : The forced swimming test(FST) was performed. The expression of corticotropin-releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN), and tyrosine hydroxylase(TH) in the ventral tegmental area(VTA) and locus coeruleus(LC) was measured with immunohistochemical method and the concentration of seum adrenocorticotropic hormone(ACTH) was measured with ELISA method. And the experimental groups were divided into the extraction after mixing(A) and mixture after extraction(B). The effects of both group were compared. Results : The duration of immobility in the forced swimming test was significantly decreased in the A400 group(P<0.01). The expression of CRF in PVN were significantly reduced in the A100, A400, B100, B400groups(P<0.001). but the expression of c-fos in PVN weren't reduced in all groups. And the concentration of ACTH in Plasma were significantly reduced in the A 100 group(P<0.01). The expression of TH in LC were significantly reduced in the A 400, B 100 and B400 groups(P<0.05~P<0.01). Conclusion : Mixture of Citri Peticulatae Viride Pericarpium and Lycii Radicis Cortex has antidepressant effects. But the difference between mixing and extracting methods was not shown.

• 동의신경정신과학회지
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• 제16권1호
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• pp.171-183
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• 2005

Objective : The Korean famous medicinal prescription of Subi-jeon was investigated for their antidepressant effects by tail suspension test, hot plate test, reserpine-induced hypothermia test. In addition, the monoamine oxidase activity was determined in vivo. Methods : The methanol extract reduced dose-dependently the duration of immobility in the tail suspension test, by 31.4 and 34%(p<0.05) at doses of 500mg/kg and 1g/kg, respectively, compared with control group. In comparison with this, the effect of the water extract was very weak. Results : 1. In the hot plate test, the methanol extract potently increased the jump latency time(p<0.05) compared to the control group, exhibiting the inhibition rate of 197% and 256% at doses of 500mg/kg and 1g/kg(per os), respectively, which is more effective than the water extract. 2. Both extracts suppressed the fall of body temperature induced by reserpine(reserpine-induced hypothermia) in a dose-dependent manner, showing the less effect at lower doses and better effect at higher doses compared to the water extract. 3. Both extracts inhibited the brain monoamine oxidase activity in an in vivo assay compared to the control group, the activity of water extract was better than that of the methanol extract. Conclusion : The prescription of Subi-jeon can be useful for the prevention and treatment of depression.

• Journal of Ginseng Research
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• 제46권3호
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• pp.376-386
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• 2022

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

• 대한본초학회지
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• 제24권4호
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• pp.143-148
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• 2009

Objectives : Anxiety and depression are stress-related disorders. Their prevalence are increasing rapidly. Ginseng is the root of Panax ginseng C.A. Meyer (Araliaceae) which has been used for many centuries in asian region. Anxiolytic effect is one of the popular effects of ginseng. Several studies reported saponin fraction of ginseng, including ginsenoside, is a major ingredient of anxiolytic effect. In present study, we investigated anxiolytic-like and antidepressant-like effect of non-saponin fraction in mice. Material and Method : Mice were divided into five groups. Experimental groups were administered non-saponin fractions (25 mg/kg; nsp25, 50 mg/kg; nsp50, 100 mg/kg; nsp100) respectively once a day in the morning at 9am for 1 week. Then, we performed elevated plus-maze (EPM) test for investigating the anxiolytic-like effect and forced swimming test (FST) for investigating the antidepressant-like action. Results : Non-saponin fraction 50 mg/kg group increased frequency and time spent (p<0.05) in open arm on EPM test and decreased immobility time (p<0.05) on FST compared with control group. Conclusions : We suggest that non-saponin fraction has anxiolytic-like effect and antidepressant like effect in mice.

• 한국임상약학회지
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• 제33권1호
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• pp.62-69
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• 2023

Objective: Adherence is an important component in the treatment of various diseases, and poor adherence to antidepressants in patients with major depressive disorder is common. Non-adherence can be more prevalent in elderly patients with multiple morbidity and polypharmacy, resulting in negative treatment outcomes. The purpose of this study was to analyze adherence to antidepressants in Korean elderly patients with major depressive disorder. Method: A retrospective study was conducted using the Korean National Health Insurance claims database, and the subjects of this study were patients aged 65 or older who received at least one prescription of antidepressant monotherapy for the treatment of major depressive disorder between January 1, 2020 and June 30, 2020. Adherence was measured using the proportion of days covered at 6 months after the initial antidepressant prescription date. Logistic regression analysis was used to identify factors associated with adherence. Results: A total of 416,766 patients were finally included in the study. Over half of patients were non-adherent (52.67%) to antidepressants. According to the multivariate logistic regression analysis, national health insurance or medical aid, taking selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors, and having comorbidities were significantly associated with greater rates of adherence in the study subjects. The highest adherence rate was observed in patients taking vortioxetine. Conclusion: There was a considerable rate of non-adherence in Korean elderly patients with major depressive disorder. Health care professionals should try to improve adherence in elderly patients with major depressive disorder.

• 한국의학물리학회지:의학물리
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• 제19권2호
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• pp.95-101
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• 2008

본 기초연구에서는 강제수영검사(forced swimming test, FST)에 의해 우울증이 유발된 쥐의 해마(hippocampus) 부위에서 뇌 대사물질(brain metabolites)중에 choline 신호의 변화를 관찰하였다. 본 연구의 목적은 우울증이 유발된 쥐에 항우울제인 desipramine-HCl을 투여하여 정상 쥐와 약물을 투여한 쥐 사이의 뇌 대사물질의 차이를 자기공명분광법(magnetic resonance spectroscopy: MRS)을 통하여 알아보는 것이다. 실험대상으로는 6주령의 SD rat을 사용하였으며 우울증을 유발시키고 항우울제의 약물평가를 위한 모델링 방법으로 강제수영검사를 시행하였다. 자기공명분광법을 시행하기 위한 localization 방법으로는 PRESS 펄스시퀀스를 사용하였다(TR: 2,500 ms, TE: 144 ms, averaging: 512, complex data point: 2048, scan time: 25 min). 정상 쥐 그룹과 우울증을 유발시킨 뒤 항우울제를 투여한 쥐 그룹 모두 양쪽 해마부위에서의 NAA/Cr, Cho/Cr 비율(ratio)은 차이가 나지 않았다. 또한 왼쪽 해마에서 정상 쥐와 항우울제를 투여한 쥐 사이에서 NAA/Cr, Cho/Cr 비율도 차이가 나지 않았고, 오른쪽 해마부위에서도 통계적으로 유의한 차이가 없었다. 본 연구를 통하여 anti-immobility효과를 나타내는 항우울제를 투여함으로써 choline 신호가 정상 쥐와 비슷하게 회복되는 것을 관찰하였다. 이는 앞으로의 항우울제 약물 평가에 있어 자기공명분광법을 도입함으로써 기존의 주관적인 판단을 배제할 수 없었던 행동변화분석만으로 항우울제의 효과를 평가하는 방법에 비해 객관적이고 정량적인 분석을 할 수 있다는 점에서 아주 유용한 방법이라 사료된다.

• 생물정신의학
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• 제8권1호
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• pp.85-95
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• 2001

This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine ${\leq}10{\mu}M$, amitriptylne ${\leq}10{\mu}M$) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine ${\geq}100{\mu}M$, amitriptyline ${\geq}100{\mu}M$) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.

• 생물정신의학
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• 제10권2호
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• pp.126-132
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• 2003

Objectives:The purpose of this study is to examine the effects of venlafaxine, one of novel antidepressant drugs, on neurite growth in PC12 cells. Methods:PC12 cells were cultured with NGF for eight days. Then different concentrations($0{\mu}M$, $1{\mu}M$, $5{\mu}M$) of venlafaxine were mixed with cultured PC12 cells. After 24 hours and 48 hours of culture, we compared the effects of venlafaxine on the total length of neurites of cultured PC12 cells between no venlafaxine treated group($0{\mu}M$) and venlafaxine treated groups($1{\mu}M$ and $5{\mu}M$). Additionally, we studied the concentration-dependent effect of venlafaxine on differentiation in PC12 cells. Results:Experimental results showed that 1) the mean length of neurites in $1{\mu}M$ and $5{\mu}M$ venlafaxine treated group was more increased than no venlafaxine treated group(p=0.002). 2) the length of neurite in $5{\mu}M$ venlafaxine treated group was more elongated than $1{\mu}M$ venlafaxine treated group(p=0.046). 3) the length of neurite in $6{\mu}M$ venlafaxine treated group was more elongated than all the other concentrations in our experiment. Above $6{\mu}M$, the length of neurite was shortened in inverse proportion to the concentration of venlafaxine. Conclusions:This results suggest that venlafaxine, one of novel antidepressant drugs, promotes the differentiation of neuron. This study is believed to be a first step toward understanding the molecular and cellular mechanisms of antidepressant treatment.