• 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.

• Biomedical Science Letters
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• v.24 no.3
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• pp.206-212
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• 2018

Depression is a type of mood disorder characterized by hypochondriasis, decreased appetite, and insomnia. Depression is a disease that affects more than 100 million people worldwide. 2-Nonadecanone (NAC) is a bioactive substance that constitutes Fomes fomentarius, and NAC is expected to have an antidepressant effect. By using the forced swimming test (FST), we investigated the effects of treatment with NAC on immobility subacutely in rats after oral dosing once a day for 2 days. Serum levels of cytokine interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-2 (Nrf-2) and inducible nitric oxide synthases (iNOS) were analyzed by western blot method. NAC dose-dependently decreased immobility in the FST. NAC dosedependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on $IL-1{\beta}$ and $TNF-{\alpha}$ levels at higher doses than the lowest dose of NAC. Western blot analysis showed that Nrf-2 was significantly lower in the NAC-treated group than in the disease-induced group. The iNOS results were also significantly lower in the NAC-treated group than in the other groups. Considering FST results, the antidepressant effect of NAC is effective. Considering the results of cytokine and protein expression, this anti-depressant effect may be related to the anti-inflammatory effect. Therefore, it can be said that the anti-inflammatory effect of NAC increases the antidepressant effect in the FST experiment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.876-880
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• 2011

Gammakdaejo-Tang (GMT) is a traditional oriental medicinal formula, a mixture of 3 crude drugs, and it has been clinically used for treating mild depressive disorders. The purpose of the study was to examine the effect of Gammakdaejo-Tang (GMT) on repeated stress-induced alterations of learning and memory on a passive avoidance test (PAT) test and also the anxiety-related behavior on the elevated pulse maze (EPM) in ovariectomized female rats. We assessed the changes in the reactivity of the cholinergic system by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral testing. The rats were exposed to the immobilization (IMO) stress for 14 days (2hours/day), and Gammakdaejo-Tang (400 mg/kg, p.o.) was administered 30 min before IMO stress. Treatments with GMT caused significant reversals of the stress-induced deficits in learning and memory on a working memory test, and it also produced an anxiolytic-like effect on the EPM, and increased the ChAT reactivities (p<0.001, respectively). These results suggest that Gammakdaejo-Tang might prove to be an effective antidepressant agent.

• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.209-220
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• 2019

Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.603-610
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• 2020

Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

• Molecules and Cells
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• v.43 no.3
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

• Journal of the Korea Convergence Society
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• v.9 no.8
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• pp.219-224
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• 2018

We have studied anemarrhena asphodeloides, a hair growth promoter as an alternative medicine agent to compensate for the disadvantages of minoxidil, which has excellent hair growth promoting effect on follicular epithelial cells. anemarrhena asphodeloide, an Rhizome plant of aemarrhena asphodeloide family, is a traditional medicinal plant used in Korea as an antipyretic, antidiabetic, antidepressant, antiinflammatory. We applied and observed anemarrhena asphodeloides ethanol extracts to the back of mice, and there was no significant difference in body weight and food intake among all groups of mice. The ethanol extract of anemarrhena asphodeloides showed vigorous hair growth promoting effect without changing the serum composition and thus it is considered to be useful as a hair growth promoter in the future.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.40-44
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• 2006

Mirtazapine is an antidepressant agent with dual action on both the noradrenergic and serotonergic neurotransmitter systems. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of mirtazapine in human plasma. A reversed-phase Cl8 column was used for the determination of mirtazapine with a mobile phase composed of 0.01M ammonium acetate solution (pH 4.2) and acetonitrile (75:25, v/v%) at a flow rate of 1.2 mL/min. Terazosin hydrochloride was used as an internal standard. The fluorescence detector was set at excitation and emission wavelengths of 290 and 350 nm, respectively. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 3 ng/mL. Mirtazapine was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study using plasma samples after oral administration of a single 30 mg dose as mirtazapine base to 8 healthy volunteers. The maximum plasma concentration of mirtazapine was $64.1{\pm}28.0ng/mL$ at 1.8 h, and the area under the curve and elimination half-life were calculated to be $674.1{\pm}218.5ng\;h/mL\;and\;23.4{\pm}3.8h$, respectively.

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.119-124
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• 2017

Taraxacum platycarpum H. Dahl. (Compositae) has been used as an anti-inflammatory or anti-cancer agent in the clinic. Although its antidepressant effect has been reported, however, its cognitive function is not investigated until yet. In the present study, we investigated whether the water extract of T. platycarpum (WETP) could improve cognitive function in cholinergic blockade-induced amnesia mouse model using the passive avoidance or Y-maze task. WETP (12.5, 25 or 50 mg/kg) significantly ameliorated the scopolamine-induced cognitive impairment both in the passive avoidance test and the Y-maze test. In addition, WETP significantly inhibited acetylcholinesterase (AChE) activity measured by an ex vivo study using the mouse whole brain. These results suggest that WETP alleviates the cognitive dysfunction caused by the cholinergic blockade, in part, via AChE inhibition, and that it may be a useful for treating cognitive dysfunction.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.81-87
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• 2019

Ketamine has long been used as an anesthetic agent. However, ketamine use is associated with numerous side effects, including flashbacks, amnesia, delirium, and aggressive or violent behavior. Ketamine has also been abused as a cocktail with ecstasy, cocaine, and methamphetamine. Several studies have investigated therapeutic applications of ketamine, demonstrating its antidepressant and anxiolytic effects in both humans and rodents. We recently reported that neonatal maternal separation causes enhanced anxiety- and aggressive-like behaviors in adolescent. In the present study, we evaluated how acute and chronic ketamine administration affected the behavioral consequences of neonatal maternal separation in adolescent mice. Litters were separated from dams for 4 hours per day for 19 days beginning after weaning. Upon reaching adolescence (post-natal day 35-49), mice were acutely (single injection) or chronically (7 daily injections) treated with a sub-anesthetic dose (15 mg/kg) of ketamine. At least 1 h after administration of ketamine, mice were subjected to open-field, elevated-plus maze, and resident-intruder tests. We found that acute ketamine treatment reduced locomotor activity. In contrast, chronic ketamine treatment decreased anxiety, as evidenced by increased time spent on open arms in the elevated-plus maze, and remarkably reduced the number and duration of attacks. In conclusion, the present study suggests that ketamine has potential for the treatment of anxiety and aggressive or violent behaviors.