• Journal of Oriental Neuropsychiatry
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• v.25 no.3
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• pp.297-310
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• 2014

Objectives: This study is designed to investigate the effects of Banhahubak-Tang Extract (BHTe) on stress. Methos: BHTe was fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100 mg/kg/day for five days. Mice were then exposed to sociopsychological stress by observing foot shock stressed mice for one hour for five days while restrained. Results: 1) The BHTe-administered group showed a tendency of decreasing of serum corticosterone secretion compared with the control group. 2) The BHTe-administered group showed an increase in noradrenalin secretions in the dorsal cortex of the brain, but it was not significant. 3) BHTe administration had no effect on the brain level of lipid peroxidation. 4) BHTe administration decreased the serum level of lipid peroxidation. 5) BHTe administration decreased the Cu,Zn-SOD in the brain. 6) BHTe administration had no effect on catalase activity in the brain. 7) BHTe administration had no effect on the brain level of GSH. 8) BHTe administration increased the serum level of DPPH free radical scavenging activity, but not significantly enough to make a comparison with BHT. 9) The elevated plus-maze test is designed to detect the effect of anxiolytic drugs. The BHTe group showed a significant increase in latency time. Conclusions: These results suggest that BHTe can effectively rid the subject of the effects of sociopsychological stress.

• Journal of Microbiology and Biotechnology
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• v.21 no.10
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• pp.1088-1096
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• 2011

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety- and depression-like behaviors and expression of corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety- and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxiety- and depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.291-298
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• 2005

Gardenia Jasminoides(GJ) is traditionally used for treatment of hepatic disease, insomnia, anxiety, and inflammatory disease. The aim of this study is to examine effects of GJ extract in response to stress. Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng and GJ supplementary group were orally administered once a day with 100mg of red ginseng extract, 100mg of GJ extract/kg body weight. The mice were given water containing 200mg of red ginseng extract, 200mg of GJ extract/100ml potable water. Animals were given supplements for 7 days without stress, and then were given supplements for 5 days with restraint and electroshock stress. After loading final stress, we examined stress related behavioral changes of experimental animals and measured the levels of blood corticosterone. GJ-supplementation partially blocked the stress effect on locomotion and elevated plus maze test in rats, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, face-washing, smelling and rearing behavior in rats. The effect was almost equipotent to Ginseng's effect. GJ-supplementation didn't influence on fatigue related behavior or physical stress resistance. GJ-supplementation decreased the levels of blood corticosterone which is increased by stress in rats. These results suggest that GJ protects partially the living organism from stress attack and it has the potential to be used as a functional material to alleviate stress response.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.81-88
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• 2012

Objective : Banhahubak-tang is indicated for globus hystericus, marked by a subjective sensation as if something stuffed in the throat, chest distress, cough or vomiting, greasy whitish, taut and smooth pulse. In this study, the effects of Banhahubak-Tang extract (BHTe) were tested for anti-stress action. Methods : BHTe was extracted by pure water using electronic extractor and then fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100mg/kg/day for five days. Mice were exposed to sociopsychological stress by restraining and seeing foot shock stressed mice for one hour for five days. Results : BHTe administered group showed a tendency of decreasing of serum corticosterone secretion when compared with control group, and BHTe administration also significantly up-regulated noradrenaline secretions in the dorsal cortex of brain. Lipid peroxidation of the brain tissues of mice were tested by measuring malondialdehyde, but BHTe showed no significant change. The elevated plus-maze test was designed to detect the effect of anxiolytic drugs, and BHTe administered group showed a significant increase of latency time. Conclusions : These results suggest that BHTe can effectively rid the psychological stress and it's related diseases.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• YAKHAK HOEJI
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• v.51 no.3
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• pp.219-227
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• 2007

Ginsenoside Rgl (Rgl), the pharmacologically active constituent of ginseng (Panax ginseng C.A. Meyer), has a variety of biological activities. The present study was undertaken to evaluate a possibility of Rgl whether it can be used in treatment or prevention of stress disorders. Animals were stressed by immobilization for 2 hours or electroshocks for 20 minutes. The normal group was not exposed to any stress. Rgl was subcutaneously injected as dosages of 5 and 10 mg/kg and red ginseng (RG) was orally administered 200 mg/kg as the positive control. Animals were given supplements for 5 days without stress, and then were given supplements for 5 days with stress. We recorded stress-related behavioral changes of experimental animals using the Etho-vision system. Weight of adrenal gland and levels of corticosterone in plasma were measured and stress related behaviors (smelling, grooming, face washing, rearing) were observed. Rgl didn't make significant behavioral changes in total open field and elevated plus maze test. Rgl did not influence on behavioral changes induced by electroshock stress. Whereas, 10 mg/kg of Rgl alleviated the increment of the freezing and face washing time and the decrement of the smelling and rearing time induced by restraint stress. The administration of Rgl 10 mg/kg has significantly increased the endurance time on rotating rod and swimming pool tests compared to the control group. These results indicate that Rgl can alleviate the damage induced by physical stress. This result suggests that Rgl may bea new candidate for treating stress related disorder.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.34-42
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• 2004

The aim of this study is to investigate anti-stress effect of Scutellaria baicalensis(SB). The experiments were performed with the use of young (9 weeks of age) male rats of SD strain and the male ICR mice (20-25 g) at the time of first treatment with SB. Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng, Diazepam(BZ) and SB supplementary group were orally administered once a day 100 mg of red ginseng extract, 5 mg of BZ or 100 mg of SB extract/kg body weight and they were exposed to stress. The mice of the Ginseng, BZ and SB supplementary group were given water containing 200 mg of red ginseng extract, 10 mg of BZ or SB extract/100 ml potable water and exposed to stress. Animals were given supplements for 7 days without stress, and then were given supplement for 5 days with restraining and electroshock stress. We recorded stress related behavioral changes of the experimental animals by stressing them using the Etho-vision system and measured levels of blood corticosterone and IL-2. SB supplementation partially blocked the stress effect on locomotion in the rats and mice, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, grooming, smelling, and rearing behavior in the rats and smelling, grooming, tailing, and rearing in the mice. in elevated plus maze test, the staying time of the stressed rats and mice in the open area decreased while it increased in the closed area. But these changes also partially were blocked by SB-supplementation. SB-supplementation decreased levels of the blood corticosterone which was increased by stress in the rats but did not significantly increase levels of blood interleukin 2 which was decreased by stress in mice.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.256-263
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• 2014

Background: Korean Red Ginseng (KRG) is known to have antianxiety properties. This study was conducted to investigate the anxiolytic effects of KRG extract (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid dopamine (DA) system in it. Methods: Rats were treated with 3 g/kg/d of ethanol for 28 d, and subjected to 3 d of withdrawal. During EW, KRGE (20 mg/kg/d or 60 mg/kg/d, p.o.) was given to rats once/d for 3 d. Thirty min after the final dose of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA). In addition, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the central nucleus of the amygdala (CeA) were also measured by high performance liquid chromatography (HPLC). Results: The EPM test and RIA revealed KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective DA D2 receptor (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R) antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of DA and DOPAC in a dose-dependent way. Additionally, Western blotting and real-time polymerase chain reaction (PCR) assays showed that KRGE prevented the EW-induced reductions in tyrosine hydroxylase (TH) protein expression in the CeA and TH mRNA expression in the ventral tegmental area (VTA). Conclusion: These results suggest that KRGE has anxiolytic effects during EW by improving the mesoamygdaloid DA system.

• Food Science and Biotechnology
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• v.15 no.1
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• pp.63-69
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• 2006

The primary objective of this study is to determine whether a diet supplemented with brown rice koji (BRK) results in a reduced stress response in rats and mice. BRK, which has been suggested as a candidate for use as a stress- and fatigue-fighting supplement, was compared with red ginseng extract (RG) for its stress-reducing potential. The animals in this study were divided into no-stress, stress, RG, and BRK groups of 8 to 10 animals each. Stress was induced by means of immobilization (being restrained in plastic tubes for 30 min and electroshock (0.5 mA in mice or 2 mA in rats for 5 min). The no-stress group was not exposed to stress. Rats in the RG group received oral doses of 200 mg RG extract/kg body weight daily. The BRK group was fed a 30% BRK diet and exposed to stress. Animals were given supplements for 7 days before being exposed to stress, and then were given supplements for 5 days with exposure to stress. When the stress exposure ended, the animals were observed for stress-related changes in behavior and their plasma corticosterone levels were measured. BRK supplementation was associated with a partial blockade of the effects of stress on locomotion and elevated plus-maze test results in rats and mice. It was also associated with a partial reduction in stress-induced behaviors such as freezing, burrowing, smelling, face-washing, and rearing. BRK supplementation did not have a significant effect on plasma corticosterone levels, which were increased in the animals exposed to stress (p<0.01). The mice in the RG group received RG in water (2 mg RG/ mL $H_2O$), and the BRK group received a 30% BRK diet (weight) for 7 days. Both groups were evaluated for signs of fatigue. BRK supplementation increased endurance, as indicated by time on the rota-rod, in cold water, and on the horizontal wire. These results suggest that BRK supplementation partially protects the animal from the effects of stress and may also contribute to resistance to fatigue on physical exertion.