• Biomolecules & Therapeutics
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• 제27권2호
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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.

• 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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• 제32권4호
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• pp.247-254
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• 2018

A This study evaluated the antidepressant effects of the herbal mixture CPAE(Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz, and Angelica gigas Nakai) using several tests, including a test for serotonin 6($5-HT_6$) receptor activity, the forced swimming test(FST), and tests for corticosterone(CORT) and monoamine levels. CPAE showed antagonistic effects on the $5-HT_6$ receptor in a stable $5-HT_6$ receptor-expressing cell line. We subsequently confirmed the antidepressant effects of CPAE in chronic stress model in mice and explored the underlying mechanisms of its action. Specifically, we observed that CPAE treatment significantly reduced immobility time in the FST and effectively restored abnormal levels of CORT in plasma and of monoamines(serotonin, dopamine, and norepinephrine) in hippocampus and prefrontal cortex. These results suggest that CPAE has significant antidepressant effects.

• 동의생리병리학회지
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• 제18권2호
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• pp.436-439
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• 2004

Mubigangjang-Ju (MGJ) is a traditional wine, fermented extract of Cynanchum wilfordii, Angelicae gigantis and Epimedium koreanum etc. In the present study, we comparatively investigated the immune-enhancing effect of fermented extract (MGJ) and water extract (WE). Forced swimming test (FST) was performed as a model of activity test in mice and measured blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), glucose (Glc) and total protein (TP) in the serum. Each extracts were orally administered into mice, 10 ㎖/kg, once per day for 7 days using a feeding atraumatic needle. After 3 days, on FST, the immobility time was decreased in the MGJ-fed group (133.7±18.6 s) in comparison with the saline-fed group (155.8±16.6 s). After 7 days, the immobility time was significantly decreased in the MGJ-fed group (105.3±12.7 s) in comparison with the saline-fed group (171.3±8.1 s). In addition, the content of AST was significantly decreased and the contents of BUN, ALT and LDH in the blood serum was also decreased. Whereas, the content of Glc tend to increase and TP level was not changed. However, WE had no effect on all experiments. The present results suggest that fermented extract was more effective than water extract and it may be useful for the immune-enhancing agent.

• 동의생리병리학회지
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• 제34권2호
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• pp.88-96
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• 2020

Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) are herbal extracts widely used in food and traditional herbal medicine, and have the ability to perform a wide range of biological activities. We aimed to investigate the effects of the SH and VB combination (SHVB) on mice models of chronic restraint stress (CRS) and pentobarbital-induced sleeping behaviors to elucidate its possible mechanisms of action. CRS-exposed mice treated with SHVB showed significantly decreased immobility time, increased swimming and climbing times in the forced swim test (FST), and increased locomotor activity in the open field test (OFT). SHVB decreased serum CORT levels, but enhanced brain monoamine neurotransmitters. SHVB significantly decreased the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behavior in mice. SHVB showed inhibitory effect on 5-HT_2A receptor-mediated ERK1/2 phosphorylation. These results suggest that SHVB has antidepressant and hypnotic effects by regulating the 5-HT_2A receptor.

• 대한본초학회지
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• 제30권3호
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• pp.69-76
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• 2015

Objectives : The effect of mixture extracted from Bupleuri Radix and Physalidis Herba(BR+RH) on the LPS-induced Depression in rats was investigated. Methods : Rats were administered intragastrically BR+PH after injectio of LPS to induce deprssion. Immobility was examined using Tail Suspension Test(TST), Forced Swimming Test(FST). The level of plasma corticosterone was measured by an Enzyme-Linked Immunosorbent Assay(ELISA) method. The expressions of c-Fos, Corticotropin Releasing Factor(CRF), NADPH-d in the Paraventricular nucleus(PVN) and TH in the Locus coeruleus(LC) were measured by immunohistochemical method. Results : In the effect of BR + PH on TST, immobility was significantly decreased comparing with the LPS group. In FST, immobility was shown decrease tendency in the BR+PH group. The expression of c-Fos in the PVN was significantly decreased at BR + PH400 group, comparing with the LPS group. The expression of CRF in PVN was shown dto have the decrease tendency in the BR+PH group, comparing with the LPS group. The expression of NADPH-d in PVN was not significantly decreased at BR+PH groups, comparing with the LPS group. The expression of TH in the LC was shown to have the decrease tendency at BR + RH groups, but not significantly, comparing with the LPS group. Conclusions : Anti-depressant effect of mixture after extracted from Bupleuri Radix and Physalidis Herba was through the anti-inflammatory effect via inhibition of HPA axis. NO and catecholamine system is not involved.

• Journal of Ginseng Research
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• 제44권4호
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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.

• 대한한의학방제학회지
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• 제27권2호
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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.

• 대한한의학방제학회지
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• 제27권2호
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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.

• Korean Journal of Acupuncture
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• 제38권2호
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• pp.75-99
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• 2021

Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.