• Journal of Ginseng Research
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• 제45권2호
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• pp.325-333
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• 2021

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

• Journal of Acupuncture Research
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• 제26권4호
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• pp.99-106
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• 2009

Objectives : The antidepressant effect of the subchronic administration of the methanolic extract of wild ginseng(WG) was investigated compared with that of cultivated ginseng(CG, panax ginseng) extract. Methods : To assess the antidepressant effect of the ginseng extracts, tail suspension test(TST) was executed in mice after daily administration of WG or CG extract for five consecutive days. Results : The WG extract at daily dose of 600mg/kg significantly reduced the total duration of immobility in the TST, whereas there was no significant reduction at daily dose of 300mg/kg WG and 600mg/kg CG. There were no individual differences between experimental groups in open field test (OFT) to evaluate psychostimulant effects of WG or CG extract. In the high performance liquid chromatography(HPLC) analysis of the extracts, it was found that WG included four times more ginsenoside Rg1 and Re, three times more Rf, and six times more Rb1 and Rc than CG. Conclusions : It is suggested that WG extract has stronger antidepressant effect than CG extract, which means it includes more antidepressant compounds than CG.

• 동의신경정신과학회지
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• 제22권2호
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• pp.129-146
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• 2011

Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.

• Journal of Microbiology and Biotechnology
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• 제22권11호
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• pp.1510-1517
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• 2012

To evaluate the probiotic potential of Bacillus polyfermenticus CJ6 isolated from meju, a Korean traditional soybean fermentation starter, its functionality and safety were investigated. B. polyfermenticus CJ6 was sensitive to all antibiotics listed by the European Food Safety Authority. The strain was also non-hemolytic, carried no emetic toxin or enterotoxin genes, and produced no enterotoxins. The resistance of B. polyfermenticus CJ6 vegetative cells and spores to simulated gastrointestinal conditions was high (60-100% survival rate). B. polyfermenticus CJ6 produced high amounts (0.36 g as a purified lyophilized form) of ${\gamma}$-polyglutamic acid (PGA). We speculate that the improved cell viability and the production of ${\gamma}$-PGA have a significant correlation. Adhesion of the strain to Caco-2 and HT-29 cells was weaker than that of the reference strain (Lb. rhamnosus GG), but it was comparable to or stronger than those of reported Bacillus spp. When B. polyfermenticus CJ6 spores were given orally to mice, the number of cells excreted in the feces was 4-fold higher than the original inocula. This suggests the inoculated spores propagated within the intestinal tract of the mice. This idea was confirmed by field emission scanning electron microscopy, which revealed directly that B. polyfermenticus CJ6 cells germinated and adhered within the gastrointestinal tract of mice. Taken together, these findings suggest that B. polyfermenticus CJ6 has probiotic potential for both human consumption and use in animal feeds.

• 대한수의학회지
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• 제44권3호
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• pp.415-420
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• 2004

Immunoprophylatic effect of IgY against B. bronchispetica was proven with 100% preventive rate in mice administrated with IgY with antibody titer 1:640~1:2,560. Intramuscular administration was more efficient than oral administration. This phenomenon was also observed in the therapeutic effects of IgY after challenge with B. bronchseptica in mice. In the field trials with the egg yolk antibodies from hens immunized with combined antigens with B. bronchiseptica and parvovirus, curing rates in dogs with severe clnical signs such as bloody diarrhea were 81.6% and 86.7% by intramuscular or subcutaneous administration of IgY, respectively. Safety of the antibodies in dogs was proven without any side effects such as vomiting, edema, fever, etc. by adminstration of double doses for 7 days. These results indicated that the egg yolk antibodies could be used as effective prevention and treatment of alimentary and respiratory diseases in dogs.

• Biomolecules & Therapeutics
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• 제27권4호
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• pp.349-356
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• 2019

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the "antidepressant" properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

• 동의신경정신과학회지
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• 제31권4호
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• pp.269-278
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• 2020

Objectives: Yukmijihwang-won (Liuweidihuang-wan in Chinese) is a frequently used medicinal herbal formula. It is used as Yin tonic in Korea and China to recover patients from Yin deficiency. However, the scientific evidence on this drug has not revealed the beneficial effect or mechanism of its effects on the neurological disorder. We designed this study to examine the antidepressive and analgesic effects of Yukmijihwang-won (YJ-01) and the minor modification of YJ-01, YJ-06 on the reserpine-induced pain-depression dyad mice model. Methods: Reserpine (1 mg/kg) was administered subcutaneously once a day for three consecutive days to induce pain and depression-like behavior. The oral administration of YJ-01 and YJ-06 (100, 200, or 300 mg/kg) was performed once daily from three days after the reserpine injection. Results: Repeated administration of the YJs significantly reduced the immobility time in a forced swimming test and increased the moved distance and number of crossings in the open field test. In the von-Frey filament test, the oral administration of YJs remarkably suppressed the increase in paw withdrawal frequency. Conclusions: The results of this study suggest that YJ-01 and 06 may be good candidates to treat the pain-depression dyad.

• 동의생리병리학회지
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• 제35권1호
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• pp.8-14
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• 2021

Shihogayonggolmoryo-tang (ST) is a Korean medical herb cocktail which has been used to treat anxiety induced insomnia. In this study, we will examine sleep-promoting and anti-anxiety effects of ST, and investigate its mechanism. ICR mice were divided into three groups for the first examination : control group (n=11), ST50 group (50 mg/kg, po, n=11), ST200 group (200 mg/kg, po, n=11). Sleep-promoting effect was confirmed by measuring the sleeping duration time and sleeping onset time after thiopental sodium treatment (50 mg/kg, ip). ICR mice were divided into five groups for the second examination : control group (n=11), ST200 group (200 mg/kg, po, n=11), ST200+Flumazenil group (ST 200 mg/kg, po, flumazenil 0.3 mg/kg, ip, n=11), diazepam group (1 mg/kg, ip, n=11), diazepam+flumazenil group (diazepam 1 mg/kg, ip, Flumazenil 0.3 mg/kg, ip, n=11). Anxiety behavior and sleep-promoting effect was confirmed by open field test and measuring the sleeping duration time and sleeping onset time. Expression levels of c-fos in tuberomammillary nucleus (TMN) and ventrolateral preoptic nucleus (VLPO) were analyzed by immunohistochemistry. ST treated group showed significantly decreased anxiety behavior and enhanced sleeping duration time and sleeping onset time concentration dependently. The expression of c-fos was significantly upregulated in VLPO as sleep-inducing center and TMN as downregulated in arousal center by ST treatment. In addition, all effects of ST were reversed by flumazenil. Our results suggest that ST has sleep-promoting and anti-anxiety effects through regulating arousal center (TMN) and sleep-inducing center (VLPO).

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.219-225
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• 2010

We tested whether ginsenosides $Rg_3$-standardized ginseng extract (RGE) has anti-stress effects in restraint-stressed animals. RGE increased time spent in the open arms and open arm entries in the elevated plus-maze test. In addition, RGE blocked the reduction of center zone distance and stereotypes behaviors in the open-field test. RGE also increased head dips in stressed mice, indicating anxiolytic-like effects. Stress decreased movement distance and duration, burrowing, and rearing frequency but increased face washing and grooming. RGE significantly reversed burrowing and rearing activity in stressed mice. In addition, we measured sleep architecture in restraint stressed rats using EEG recorder. Stress increased rapid eye movement (REM) sleep, but total sleep and non-rapid eye movement (NREM) sleep were not changed. RGE did not affect sleep architecture in stressed rats. These behavioral experiments suggest that RGE has anti-stress effects in restraint-stressed animal models.

• 생물정신의학
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• 제9권1호
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• pp.8-14
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• 2002

Patients with attention deficit hyperactivity disorder(ADHD) have symptoms of inattention, hyperactivity, impulsivity. Symptoms of ADHD are responsive to medications such as methylphenidate, dextroamphetamine, pemoline, and bupropion. The functional change of the dopamine transporter is related to the therapeutic effect of these drugs. This can be one reason for the dopamine transporter to be emphasized in the research field of ADHD. ADHD has a genetic tendency. Since dopamine transporter gene(DAT1) knock out mice were reported to be several times more active than normal mice in a novel situation, lights has been shed on DAT1 as a candidate gene for ADHD. Though there have been several studies which reported an association between DAT1 and ADHD, the association between DAT1 and ADHD is not conclusive. Since Vandenbergh reported the DAT1 polymorphism with variable number of tandem repeats(VNTR), and the racial differences in allelic frequencies of the DAT1, wide ethnic variation in the distribution of the DAT1 polymorphism had been confirmed. Wide ethnic variation in the distribution of the DAT1 suggested that there might be ethnic difference in the association between DAT1 and ADHD. Before applying previous findings to Koreans, verification might be needed for Korean patients with ADHD.