• 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.

• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.708-720
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• 2012

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stress-induced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced open-arm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

• Journal of Microbiology and Biotechnology
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• v.22 no.3
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• pp.422-430
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• 2012

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxiety-like behaviors and alters the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamic-pituitary-adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

• 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.

• Animal cells and systems
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• v.14 no.4
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• pp.253-259
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• 2010

Artemisia capillaris Thunb. is widely used in the herbal medicine field. This study describes the antidepressant effect of a flavonoid (chlorogenic acid) isolated from the Artemisia capillaris Thunb. The expression of the pituitary gland and hypothalamic POMC mRNA or plasma ${\beta}$-endorphin levels were increased by extract of Artemisia capillaris Thunb. or its flavoniod administered orally. In addition, antidepressant activity was studied using the tail suspension test (TST), the forced swimming test (FST) and the rotarod test in a chronically restrained immobilization stress group in mice. After restraint stress (2 h/day for 14 days), animals were kept in a cage for 14 days without any further stress, but with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with chlorogenic acid (30 mg/kg/day). POMC mRNA or the plasma ${\beta}$-endorphin level was increased by the extract of Artemisia capillaris Thunb. and its flavoniod. In addition, the immobility time in TST and FST was significantly reduced by chlorogenic acid. In the rotarod test, the riding time remained similar to that of the control group at 15 rpm. Our results suggest that the flavonoid (chlorogenic acid) isolated from Artemisia capillaris Thunb. shows a potent antidepressant effect.

• Korean Journal of Food Science and Technology
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• v.41 no.4
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• pp.413-416
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• 2009

The sap of the white birch is one of the most widely used herbal medicines to treat gastrointestinal tract, jaundice, and various periodontal diseases. The purpose of this study was to measure the effect of white birch sap on in vivo immune agents in mice. The treatment of white birch sap on the forced swimming test has been used as a screening model for new immune enhancement agents. The hematological examination was significantly different in neutrophil, lymphocyte, and monocyte counts between treatment and control groups. Moreover the white birch sap changed the phagocytic index, immobility duration time, and leukocyte counts in mice.

• Journal of Sasang Constitutional Medicine
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• v.26 no.2
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• pp.165-179
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• 2014

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

• Herbal Formula Science
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• v.27 no.2
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• pp.121-136
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• 2019

Objective : To investigate the effect of sihogayonggolmoryeotang (SY) on Single Prolonged Stress(SPS)-induced Post Traumatic Stress Disorder(PTSD). Method : To confirm the effects of SY on SPS-induced PTSD, Changes in body weight, sucrose intake open field test(OFT) and forced swimming test(FST)were observed. After behavioral tests, the plasma corticosterone(CORT) from the abdominal aorta, serotonin(5-HT) from prefrontal cortex, hippocampus, amygdala and striatum, norepinephrine(NE) and dopamine(DA) from hippocampus was measured by ELISA. mRNA expression of brain-derived neurotrophic factor(BDNF) and cAMP response element-binding protein(CREB) in hippocampus was measured by RT-PCR. Result : Weight change and sucrose intakes of rats in 14th day after the administration of SY were significantly increased in the SPS + SY450 group compared to the SPS group (p<0.05). Numbers of crossing in the central zone in the OFT were significantly increased in the SPS + SY450 group (p<0.05) compared with the SPS group. The immobility time of FST was significantly decreased in SPS + SY450 group compared with SPS group (p<0.05). The change of plasma CORT concentration was significantly decreased in SPS + SY450 group compared with that in SPS group (p<0.05). The change of 5-HT concentration was significantly increased in the SPS + SY450 group at hippocampus and amygdala compared with the SPS group (p<0.05). The concentration of DA was significantly increased in the SPS + SY450 group compared with the SPS group (p<0.05). The expression of BDNF and CREB were significantly increased in SPS + SY450 group compared with the SPS group (p<0.05). Conclusion : SY administration lowered the increase of CORT caused by PTSD and increases the 5-HT concentration and reversed the decreased expression of NE and DA and BDNF and CREB by PTSD. It is postulated that SY is effective in treating PTSD by restoring cognitive function, memory impairment, unstable emotional disturbances.

• Herbal Formula Science
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• v.27 no.2
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• pp.137-149
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• 2019

Objective : This study is conducted in order to investigate the effect of Banggibongnyeongtang(BBT) on Lipopolysaccharide (LPS)-induced depression. Method : LPS $5{\mu}g$ was injected to lateral ventricle. Experimental groups were administered BBT intraperitoneally. Depressive behavior was confirmed by weight change, sucrose preference, open field test(OFT), and forced swimming test(FST). The plasma concentration of $IL-1{\beta}$ and $TNF-{\alpha}$, Corticotropin-Releasing Factor(CRF), Adrenocorticotropin Hormone(ACTH) and Corticosterone(CORT) were measured by ELISA. Result : BBT did not change the body weight significantly than LPS group, but on sucrose preference, BBT increased significantly in LPS+BBT400 group compared to LPS group (P<0.05). In the OFT, BBT increased spending time in the central zone and decreased grooming number. LPS+BBT400 group increased central zone-spending time, and decreased grooming number than LPS group significantly (P<0.05). In the FST, LPS+BBT400 group decreased immobility time than LPS group significantly (P<0.05). BBT decreased $IL-1{\beta}$ concentration does-dependently, but only with significant decrease in LPS+BBT400 group than LPS group in plasma (P<0.05). But BBT did not decrease $TNF-{\alpha}$ concentration significantly in plasma. BBT decreased plasma CRF, ACTH, and CORT. And CRH and CORT of LPS+BBT400 group were shown significant decrease comparing with LPS group (P<0.05). Conclusion : It is postulated that the anti-depressant effect of BBT can be validated through inhibition of HPA axis abnormal activity by the anti-inflammatory effect.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.160-167
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• 2019

Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.