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Protective Effects of Silibinin and Its Possible Mechanism of Action in Mice Exposed to Chronic Unpredictable Mild Stress

  • Yan, Wen-Jing;Tan, Ying-Chun;Xu, Ji-Cheng;Tang, Xian-Ping;Zhang, Chong;Zhang, Peng-Bo;Ren, Ze-Qiang
    • Biomolecules & Therapeutics
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    • v.23 no.3
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    • pp.245-250
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    • 2015
  • Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors

  • Han, Jing;Wang, Dong-sheng;Liu, Shui-bing;Zhao, Ming-gao
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.291-297
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    • 2016
  • Cytisine (CYT), a partial agonist of ${\alpha}4{\beta}2-nicotinic$ receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.

The Effects of Aquatic Excercise Program on the Physical Function and Depression in Community Elderly (수중운동 프로그램이 지역사회 노인의 신체기능과 우울에 미치는 영향)

  • Jang Soongnang
    • Journal of Korean Public Health Nursing
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    • v.14 no.1
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    • pp.122-130
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    • 2000
  • This study was designed to investigate the effects of an aquatic exercise program on the physical function and depression among the community elderly. The subjects were 41 cases of aged over 65 who went to elderly college in Hawsung-Kun, Kyeongkee province. Seventeen of them were assigned to control group, while twenty four subjects to the experimental group. The period of data collection was from June., 1999 to November., 1999. The aquatic exercise program was developed by the author with the assistance of rehabilitation medicine doctor and physical therapist in the public health center. The program was carried out once a week for 6 months in regular swimming pool. Data were analyzed with t-test, $X^2$ test, ANCOVA. paired t-test using SAS 6.12. Results were obtained as follows: 1. The increments in the range of motion of the shoulder and knee joints in experimental group after exercise was significantly greater than those in the control group. 2. The physical pain score decreases significantly after the exercise in the experimental group only. 3. The experimental group revealed lower level of depression after exercise than the level before the exercise, whereas control group showed no significant changes in this level. These findings may indicate that the aquatic exercise program is effective in increasing the range of motion of shoulder and knee joints and also effective in decreasing pain, the level of depression. Accordingly. the aquatic exercise program can be adopted as an health promotion program for community elderly.

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Dehydroevodiamine.HCl Improves Stress-Induced Memory Impairments and Depression Like Behavior in Rats

  • Kim, Hee Jin;Shin, Ki Young;Chang, Keun-A;Ahn, Sangzin;Choi, Hee Soon;Kim, Hye-Sun;Suh, Yoo-Hun
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.1
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    • pp.55-59
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    • 2014
  • Dehydroevodiamine HCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impairment and depression induced by stress.

The Effects of Koamsimsinwhan(without Cinnabarite) on Depression in Chronic Mild Stress(CMS)-treated Rats (고마심신환거주사방(古魔心賢丸去朱砂方)이 우울증(憂鬱症) 모형(模型) 흰쥐의 우울(憂鬱) 성향 및 PVN 의 c-Fos 발현(發顯)에 미치는 효과(效果))

  • Kim, Jong-Woo;Whang, Wei-Wan;Kim, Hyun-Taek;Lee, Jae-Hyok
    • Journal of Oriental Neuropsychiatry
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    • v.13 no.2
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    • pp.107-119
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    • 2002
  • This study was performed to evaluate the effects of Koamsimsinwhan (without Cinnabarite) on depression in CMS-treated rats. Rats of trial groups were exposured to chronic mild unpredictable stress for 4 weeks. These CMS-treated rats were stratified into Koamsimsinwhan(without Cinnabarite) group and vehicle(non-drug) group. And there were control rats excluding both CMS and Koamsimsinwhan(without Cinnabarite). Forced swimming test, general activity test and immunohistochemical test(measuring the level of manifestation of c-Fos in PVN) were executed to evaluate the effects of Koamsimsinwhan(without Cinnabarite) on depression after 4 weeks of CMS treatment. The results were as follows 1. In FST, depression was induced from CMS treatment and was supressed with Koamsimsinwhan(without Cinnabarite). 2. The increased activity of nerve cell in PVN, which refers to stress, was induced from CMS treatment and normalized with Koamsimsinwhan (without Cinnabarite).

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Scolopendra Pharmacopuncture Ameliorates Behavioral Despair in Mice Stressed by Chronic Restraint

  • Choi, Yu-Jin;Lee, Hwa-Young;Kim, Yunna;Cho, Seung-Hun
    • Journal of Pharmacopuncture
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    • v.20 no.4
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    • pp.257-264
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    • 2017
  • Introduction: Pharmacopuncture, which combines acupuncture with herbal medicine, is one of the newly developed acupuncture techniques that has recently been put into use. The possible mechanisms of scolopendra pharmacopuncture, as well as its potential effects on depressive symptoms, were investigated in this study by using a mouse model of chronic immobilization stress (CIS). Methods: C57BL/6 male mice were randomly assigned into three groups: mice not stressed with restraint and injected with distilled water, mice stressed with restraint and injected with distilled water, and mice stressed with restraint injected with scolopendra pharmacopuncture at a cervical site. Behavioral tests (an open field test, tail suspension test, and forced swimming test) were carried out after two weeks of CIS and injection treatments. The expression levels of glial fibrillary acidic protein (GFAP) in the hippocampus were determined by using western blot and immunohistochemistry analyses. Results: Mice exposed to CIS showed decreased behavioral activity, while scolopendra pharmacopuncture treatment significantly protected against the depressive-like behaviors induced by CIS. Moreover, scolopendra pharmacopuncture treatment increased GFAP protein levels in the hippocampi of the mice stressed by chronic immobilization. Conclusion: Scolopendra pharmacopuncture has an ameliorating effect on depressive behavior, which is partially mediated through protection against glial loss in the hippocampus.

Comparison of Nelumbinis Semen Extract with Hypericum Perforatum and Fluoxetine in Animal Model of Depression (연자육의 항우울 효과 및 프로티옴 분석을 통한 기전 연구)

  • Lee, Jin-Woo;Hong, Moo-Chang;Shin, Min-Kyu;Bae, Hyun-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.830-843
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    • 2006
  • Clinical evidence suggests that Nelumbinis Semen extracts have antidepressive properties and may offer an interesting alternative for the treatment of mood disorders. It was the aim of the present study to compare the effects of Nelumbinis Semen extracts with those of fluoxetine and hypericum perforatum extract in the rat forced swimming test (FST) and chronic mild stress (CMS), a model of depression. In the FST, p.o. administration of Nelumbinis Semen extracts (1 mg) induced a statistically significant reduction of immobility. The active behaviors in that test did not reflect decreased general activity because Nelumbinis Semen extracts failed to alter the locomotor activity of rats, measured in the open field test. Moreover Nelumbinis Semen extracts was superior to fluoxetine and hypericum perforatum extract in the incidence of sexual side-effects. These effects of Nelumbinis Semen extracts on the rat behavior is to be ascribed to increased Cytochrome c oxidase polypeptide Vla-liver, Mitogen-activated protein kinase 1 , Adenylosuccinate synthetase, and Aldehyde dehydrogenase in rat hippocampus.

The Ameliorating Effect of Kyung-Ok-Go on Menopausal Syndrome Observed in Ovariectomized Animal Model (난소 절제 동물모델을 이용한 경옥고의 갱년기 증후군 개선 효과)

  • Cho, Kyungnam;Jung, Seo Yun;Bae, Ho Jung;Ryu, Jong Hoon
    • Korean Journal of Pharmacognosy
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    • v.51 no.4
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    • pp.310-316
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    • 2020
  • Kyung-Ok-Go (KOK) is a traditional prescription used for debilitating natural aging and post-illness debilitation. KOK has been used in a variety of ways because it strengthens immunity, prevents illness, and helps recovery in case of illness. In particular, recent research has revealed that KOK helps improve memory and cognition. Therefore, in this study, we investigated whether KOK was effective in improving memory decline and depression-state observed during menopause. In the present study, we employed ovariectomized mouse as an animal model for measuring menopausal syndrome. The administration of KOK for 8 weeks, the object recognition memory and working memory were improved in novel object recognition test and Y-maze test. And in the forced swimming test, the immobility time were decreased. Additionally, the expression level of mature brain derived neurotropic factor (mBDNF) was increased by KOK administration in ovariectomized mouse hippocampus. These results suggested that KOK could improve cognitive decline and depression during menopausal period, and it might be come from enhancing expression level of mBDNF in hippocampus.

Antistress effect of Gagamsanzointang on rat chronic stress model (가감산조인탕(加減酸棗仁湯)이 만성 스트레스 모델 쥐에 대한 항스트레스 효과)

  • Kwon, Hyuk-Jin;Kim, Kyeng-Sub;Kang, Su-Kueng;Park, Pil-Sang;Yu, Ji-Yeon;Lim, Ji-Min;Cho, Yong-Sik;Choi, Yoon-Hee;Park, Shin-Young
    • The Korea Journal of Herbology
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    • v.27 no.6
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    • pp.29-35
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    • 2012
  • Objectives : To observe the effect of 4 kinds of Korean medicine and complex extracts on the anti-stress of chronic mild stress Rat model, so as to find out the machanism of its pharmacological effects. Methods : 64 healthy SD Rats were randomly divided into 8 groups. Model Design by chronic stress(CSM), and carried out the forced swimming test. We investigated the body weight, feed and water intake, feed conversion ratio and measured parameters to changes in swimming time, immobility time, 2 and 24 hours of feces, corticosterone hormone and blood glucose level. Results : In this experiments, body weight gain and feed intake were higher in all korean medicinal herb group. Swimming time were increased by Zizyphus jujuba and Gagamsanzointang(SZT) groups and immobility time was significantly lower by Zizyphus jujuba and Fluoxetine(FLX) groups. The result of corticosterone hormone level were significantly lower in Fluoxetine(FLX) and Gagamsanzointang(SZT) but blood glucose was not significantly difference. In 2 hours after fecal frequency result were significantly lower in Zizyphus jujuba group. but SZT group were increased. This result caused by acute stress but 24 hours of feces were restored to normal. Conclusions : 5 kind of Korean Medicinal Herbs extracts has good anti-stress effects, and also to clear the circulatory system and regulate blood glucose and improve bowel function. We suggest that use a single Korean medicine rather than the combination to relieve stress.

The Physiological Activities of Kyung Ok-Ko(II) -Effects on the Hyperglycemia, Hypertension, Anti-Fatigue and Decrease of Body Weight- (경옥고의 생리활성 (II) -고혈당, 고혈압, 지구력 및 체중감소에 미치는 영향-)

  • Whang, Wan-Kyunn;Oh, In-Se;Lee, Suk-Hee;Choi, Soo-Bu;Kim, Il-Hyuk
    • Korean Journal of Pharmacognosy
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    • v.25 no.1
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    • pp.51-58
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    • 1994
  • The studies were conducted to investigate the anti-diabetic activities on the hyperglycemia induced by streptozotocin in rats, anti-hypertensive activities in SHR, anti-fatigue and decrease of body weight activities in mice by Kyung Ok-Ko water extract and drink, which is a traditional preparation in Korea. 1. The blood glucose levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses(300, 600, 1200 mg/kg) of Kyung Ok-Ko water extract. Particularly, administration of 600, 1200 mg/kg were significantly shown to decrease glucose levels comparing with control group. 2. The serum total cholesterol levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses(300, 600, 1200 mg/kg) of Kyung Ok-Ko water extract. Particularly, administration of 600, 1200 mg/kg were significantly shown to decrease total cholesterol levels comparing with control group. 3. The serum triglyceride levels of streptozotocin-induced hyperglycemic rats were dose-dependently decreased by administrations of various doses(300, 600, 1200 mg/kg) of Kyung Ok-Ko water extract. Particularly, administration of 600, 1200 mg/kg were significantly shown to decrease triglyceride levels comparing with control group. 4. The blood pressure in SHRs were dose-dependently lower descended by administration of Kyung Ok-Ko water extract 300, 600, and 1200 mg/kg, respectively. 5. The swimming time of Kyung Ok-Ko water extract(100, 200, 400 mg/kg) and drink(0.7, 1.4, 2.1 ml/kg) were significantly extended to all experimental group dose-dependantly. 6. The decrease of body weight of Kyung Ok-Ko water extract(100, 200, 400 mg/kg) and drink(0.7, 1.4, 2.1 ml/kg) were significantly evaluated dose-dependently in all experimental group.

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