• The Korea Journal of Herbology
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• v.25 no.2
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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.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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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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• v.46 no.3
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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.

• The Korea Journal of Herbology
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• v.24 no.4
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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.

• Korean Journal of Clinical Pharmacy
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• v.33 no.1
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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.

• Progress in Medical Physics
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• v.19 no.2
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• pp.95-101
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• 2008

In this study, we observed the alteration of choline signal intensity in hippocampus region of the depressive rat model induced by forced swimming test (FST). The purpose of this study was to evaluate the antidepressant efficacy in the depressive animal model using MR spectroscopy. Fourteen experimentally naive male Sprague-Dawley rats weighting $160{\sim}180\;g$ were used as subjects. Drug injection group was exposed to the FST except for control group. The drugs were administered subcutaneously (SC) in a volume equivalent to 2ml/kg. And three injections were administered 23, 5, and 1h before beginning the given test. 1H MR spectra were obtained with use of a point resolved spectroscopy (PRESS) localization sequence performed according to the following parameters: repetition time, 2500 ms; echo time, 144 ms; 512 average; 2048 complex data points; voxel dimensions, $1.5{\times}2.5{\times}2.5\;mm^3$ ; acquisition time, 25min. There were no differences in NAA/Cr and Cho/Cr ratio between the right and the left hippocampus both normal control rats and antidepressant-injected rats. Also, no differences were observed in NAA/Cr and Cho/Cr ratio between the normal control rats and the antidepressant-injected rats both the right and the left hippocampus. In this study, we found the recovery of choline signals in the depressive animal model similar to normal control groups as injecting desipramine-HCl which was antidepressant causing anti-immobility effects. Thus, we demonstrated that MR spectroscopy was able to aid in evaluating the antidepressant effect of desipramine-HCl.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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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.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.107-115
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• 2018

Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and $N_{\omega}$-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.

• Korean Journal of Biological Psychiatry
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• v.26 no.2
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• pp.39-46
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• 2019

Antidepressants are widely used to treat depression in Korea, however, only a few studies have focused on the provider of the treatment. The aim of the study is to compare the differences between patients who were prescribed antidepressants by psychiatrists and those who were prescribed antidepressants by non-psychiatrists in South Korea. Patients with a diagnosis of depressive disorder who had been newly prescribed antidepressants in 2012 were selected from the Health Insurance Review and Assessment Service database. They were classified into two groups depending on whether they received the antidepressant prescription from a psychiatrist or non-psychiatrist. Sociodemographic, clinical, and depression related cost has been investigated. Treatment resistant depression, which is defined as a failure of two antidepressant regimens to alleviate symptoms, was also investigated. Prescription adequacy was assessed based on whether a regimen was maintained for at least 4 weeks. Among the 834694 patients with pharmaceutically treated depression (PTD) examined in this study, 326122 (39.1%) were treated by psychiatrists. Patients who were treated by psychiatrists were younger and had more psychiatric comorbidities than those treated by non-psychiatrists. They had longer PTD duration (229.3 days vs. 103.0 days, p < 0.05) and a larger proportion of treatment resistant depression (9.3% of PTD) when compared to those patients treated by non-psychiatrists. The patients treated by psychiatrists had a smaller proportion of inadequate antidepressant use compared to those patients in the non-psychiatrist group (44.5% vs. 65.1%, p < 0.05). The costs related to depression corrected with PTD duration were higher in the non-psychiatrist group (32214 won vs. 56001 won, p < 0.05). Patients who receive antidepressants from psychiatrists are patients with more severe, treatment-resistant depression. Psychiatrists prescribe antidepressants more adequately and cost- effectively than non-psychiatrists.