• 약학회지
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• 제38권6호
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• pp.733-741
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• 1994

To detect anxiolytic activity from Sanguisorbae Radix we used various animal models of fear or anxiety that are sensitive to known anxiolytic drugs. While diazepam showed significant anxiolytic activities in all five animal models empolyed in this study, $5-HT_3$ antagonist ondansetron and ethylacetate fraction of Sanguisorbae Radix did show anti-anxiety effects in social interaction and two compartment exploration tests. Ethylacetate fraction of Sanguisorbae Radix and 5-HT related drugs like ondansetron and buspirone, however, seem to have merit over diazepam in terms of not causing drowsiness. Among ten subfractions obtained from ethylacetate fraction of Sanguisorbae Radix by silica gel chromatography, subfraction I showed higher anxiolytic activities than subfraction DEF in two animal models, social interaction and two compartment exploration tests. There is growing evidence for the role of 5-HT in the control of anxiety. We hope that new compound(s) will be found from the active fractions of Sanguisorbae Radix as a potential anxiolytic agent in the future.

• Journal of Ginseng Research
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• 제46권6호
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• pp.819-829
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• 2022

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABA_A antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABA_A receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.156-164
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• 2005

This study was performed to investigate the anxiolytic-like effects Panax ginseng in mice using the elevated plus-maze model. Furthermore, the anxiolytic-like effects of Panax ginseng were compared to a known active anxiolytic drug, diazepam. Ginseng total saponin (GTS, 100 mg/kg) from red ginseng (RG), sun ginseng (SG) total extract (50 mg/kg), butanol fraction of SG(25 and 50 mg/kg) and ginsenosides ($Rb_1,\;Rg_1,\;and\;Rg_5$ and Rk mixture) significantly increased the number of open arm entries and the time spent on the open arm, compared with that of control. However, Red ginseng (RG) total extract (l00 mg/kg), GTS (25, 50 mg/kg), SG total extract (25 mg/kg) and ginsenosides ($Rg_{3}-R\;and\;Rg_{3}-S$) did not increase the number of open arm entries and the time spent on the open arm. On the other hand, butanol fraction of RG (l00 mg/kg), total extract of SG (50 mg/kg), butanol fraction of SG (50 mg/kg), ginsenosides ($Rb_{1},\;and\;Rg_{5}$ and Rk mixture) decreased the locomotor activity, in a similar fashion to diazepam. These data support that ginseng has the anxiolytic-like effects and the anxiolytic potential of SG was stronger than that of RG. Ginsenosides $Rb_{1},\;Rg_{1},\;and\;Rg_{5}$ and Rk mixture play important role on the anxiolytic-like effects of Panax ginseng. We provide evidence that ginseng and some ginsenosides may be useful for the treatment of anxiety.

• Journal of Ginseng Research
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• 제31권4호
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• pp.217-221
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• 2007

Ginseng has been widely used for the management of anxiety and emotional instability, but there is little experimental evidence supporting these clinical applications. The anxiolytic-like effect of ginseng saponin and polysaccharide fractions of white (WG) and red ginsengs (RG) was investigated using the elevated plus-maze test. The saponin (SF) and polysaccharide (PF) fractions were orally administered to male ICR mice for 3 days and behavioral test for the anxiolytic activity were performed. SF significantly increased the time-spent open arms and number into the in the open arm entries. However, PF weakly increased the time-spent in the open arms, but did not increase number into the open ann entries. The WG showed more potent anxiolytic-like effect than that of RG. The anxiolytic-like activities were antagonized by flumazenil, but not by esmolol. These findings suggest the saponin fractions of WG and RG promote the anxiolytic-like activity by antagonizing GABN/benzodiazepine receptors in mice.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.125-130
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• 2001

Shin-Ki-Hwan (Shen-Qi-Wan, SKH), Bo-Jung-Ik-Ki-Tang (Bu-Zhong-Yi-Qi-Tang, BJIKT), and Sa-Mul-Tang (Si-Wu-Tang, SMT) have been used for various kinds of deficiency syndromes, such as 'yang', 'qi', and 'blood', respectively. The objects of this study were to determine the effects of water extracts of three different kinds of traditional Chinese medicine (TCM), SKH, BJIKT, and SMT, on the anxiolytic activities in the elevated plus-maze test and to clarify the differences among 'yang', 'qi', and 'blood'. The water extracts of SKH, BJIKT, and SMT were orally administered to male SD rats, at 1.0 g/kg for 10 days. All rats were subjected to behavioral tests for the anxiolytic activity at 10 days. SKH, for the benefiting 'yang'agents, significantly increased the ratio of open arms entry to the total arms entry and time spent in the open arms (p<0.05), suggesting anxiolytic effect. However, both BJIKT and SMT decreased the ratio of open arms entry to the total arms entry and increased times spent in the closed arms (p<0.05). From these findings, it can be speculated that SKH only exhibits anxiolytic effect and that the different anxiolytic effects in the elevated plus-maze test may be come from the meanings of 'yang', 'qi', and 'blood'in oriental diagnostics though the cases are restricted.

• 생물정신의학
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• 제4권1호
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• pp.102-107
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• 1997

홍삼사포닌분획의 항불안작용의 양상을 검색하고자 사포닌분획을 사용하여 실험 동물에서 항불안작용을 검색하고 이들의 작용을 benzodiazepine의 대표적 약물인 diazepam의 효과와 비교하여 보았다. 실험동물에서 항불안효과의 검정을 위하여 생쥐에게 각각 상이 한 단일성분 함량을 지닌 여러분획들을 투여 후 elevated plus maze법을 사용하여 항불안효과를 비교, 관찰하였다. 실험결과 홍삼 ginsenoside Rg1, Rf 및 Re 등의 함량이 보다 높은 TSI 분획에서 항불안 효과를 관찰하였다. 중추신경계에 작용하여 진정효과를 나타내는 약물 중 특히 항불안제의 작용에 관여하는 신경전달물질 수용체로 현재까지 가장 주목을 받고 있는 것은 GABA A-benzodiazepine 수용체-chloride통로 복합체에 있는 benzodiazepine 수용체이다. 본 실험결과 관찰한 홍삼 사포닌의 항불안작용의 기전 규명을 위한 접근방법으로 홍삼 사포닌의 benzodiazepine 수용체에 대한 수용체 결합력을 관찰하고자, 흰쥐의 대뇌 피질을 검체로 하여 benzodiazepine 수용체에 대한 [$^3H$] Ro15-1788 결합 실험을 실시하였다. 홍삼 사포닌 분획들은 benzodiazpine 수용체에 결합하는 반응성을 보였으며, ginsenoside Rb, Re 및 Rd등의 함량이 높은 TSIV 분획이 가장 높은 결합력을 나타내었는데, 이 분획에서는 항불안 작용을 관찰할 수 없었다. 이상의 결과에서 볼 때 홍삼사포닌은 항불안작용을 나타내었으며, 이 항불안작용과 benzodiazepine 수용체에 대한 결합력과의 연관성은 관찰되지 않았다.

• Advances in Traditional Medicine
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• 제5권4호
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• pp.301-307
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• 2005

The roots of the plant Korean ginseng have been extensively used in the traditional Chinese herbal medicine. We investigated the standardized extract of Korean ginseng on animal models of anxiety based on exploratory behavior. Korean ginseng extract (KGE) (3, 10 and 30 mg/kg) was administered intra-peritoneally. The anxiolytic activity was studied using elevated plus maze (EPM) paradigm, light/dark apparatus (LDA), open field apparatus (OFA) and the hole board apparatus (HBA). Diazepam (1mg/kg) was used as a standard anxiolytic drug. In EPM, KGE (10 mg/kg) significantly (P < 0.05) increased the time spent in open arms and the number of entries in open arms. In LDA, KGE (10 mg/kg) increased the number of transitions. In OFA, KGE (3 and 10 mg/kg) significantly increased (P < 0.05) the number of squares traversed. In HBA the number of head pokes were significantly increased with KGE (3 and 10 mg/kg). KGE at all selected doses did not affect the motor coordination. Thus, the study suggests that saponin containing standardized Korean ginseng extract possess anxiolytic activity.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.261-269
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• 2008

This experiment was performed to investigate the anxiolytic-like effects of cyclopeptide fraction alkaloids of Zizyphi Spinosi Semen (CFAZ), by using the experimental paradigms of anxiety, and compared with those of a known anxiolytic, diazepam. CFAZ (8.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of center zone ambulatory time in the open-field box. However, CFAZ has no effect on the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly reduced locomotor activity. CFAZ did not influence the grip force in the grip strength meter test, either. From the molecular experiments, CFAZ increased chloride influx in cultured cerebellar granule cells. In addition, $GABA_A$ receptors $\gamma$-subunit were over-expressed by CFAZ in cultured cerebellar granule cells. It is concluded that CFAZ may have anxiolytic-like effects, and these effects may be mediated by $GABA_A$ receptors.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• Natural Product Sciences
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• 제15권3호
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• pp.115-120
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• 2009

Woohwangcheongsimwon (WHCSW) is a traditional oriental medicinal fomula which has been clinically used for treating strokes, palpitation, loss of consciousness and anxiety. The purpose of this study was to characterize the putative anxiolytic properties of WHCSW using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). In the EPM test, WHCSW significantly increased the percentage of time-spent in the open arms (200 mg/kg, P < 0.05) and the percentage of open arm entries (200 and 400 mg/kg, P < 0.05). WHCSW also significantly increased the number of head-dips in the hole-board test (200 mg/kg, P < 0.05). In addition, the anxiolytic properties of WHCSW examined in the EPM test were inhibited by flumazenil (10 mg/kg, i.p.), a GABA$_A$ antagonist. However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus 10% Tween 80 controls. These results suggested that WHCSW is an effective anxiolytic agent, and that its anxiolytic effects are mediated via GABA$_A$ receptors.