The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass)

Ethnopharmacological relevance

The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system.

Materials and methods

The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT_1A receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment.

Results

The present work found anxiolytic-like activity of the EO at the dose of 10 mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LDB, indicating that the EO activity occurs via the GABA_A receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus.

Conclusions

The results corroborate the use of Cymbopogon citratus in folk medicine and suggest that the anxiolytic-like effect of its EO is mediated by the GABA_A receptor-benzodiazepine complex.     

Anxiolytic-like effect of lavender essential oil inhalation in mice: Participation of serotonergic but not GABAA/benzodiazepine neurotransmission

Ethnopharmacological relevance

Lavandula angustifolia (lavender) inhalation has been used in folk medicine for the treatment of anxiety, and clinical and animal studies have corroborated its anxiolytic effect, although its mechanism of action is still not fully understood.

Aims of the study

The objective of the present study was to determine whether the GABA_A/benzodiazepine complex or serotonin neurotransmission mediates the anxiolytic-like effect of lavender essential oil.

Materials and methods

Male Swiss mice were subjected to the marble-burying test after being exposed to the aroma of lavender essential oil (1–5%), amyl acetate (5%; used as a behaviorally neutral odor), or distilled water for 15 min via inhalation. Additionally, the effect of 5% lavender essential oil was also evaluated in mice subjected to the elevated plus maze. GABA_A/benzodiazepine mediation was evaluated by pretreating the mice with the GABA_A receptor antagonist picrotoxin before the marble burying test and [³H]flunitrazepam binding to the benzodiazepine site on the GABA_A receptor. Serotonergic mediation was studied by pretreating the mice with O-methyl-[3H]-N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635), a serotonin 5-HT_1A receptor antagonist before the marble burying test. We also evaluated changes in the pharmacologically induced serotonin syndrome and the effects of combined administration of subeffective doses of lavender essential oil and the 5-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

Results

Lavender essential oil (1–5%) decreased the number of marbles buried compared with the control and amyl acetate groups. In the elevated plus maze, 5% lavender essential oil inhalation increased the percentage of time spent on and number of entries into the open arms compared with controls. No effect was seen in the number of closed arm entries or number of beam interruptions in the automated activity chamber. Pretreatment with the GABA_A receptor antagonist picrotoxin (0.5 mg/kg) did not modify the behavioral effect of 5% lavender essential oil in the marble-burying test. Lavender essential oil also did not alter [³H]flunitrazepam binding to the benzodiazepine site on the GABA_A receptor. Pretreatment with the serotonin 5-HT_1A receptor antagonist WAY100635 (3 mg/kg) blocked the anxiolytic-like effect of lavender essential oil and the 5-HT_1A receptor agonist 8-OH-DPAT (3 mg/kg). A combination of ineffective doses of 8-OH-DPAT (0.5 mg/kg) and lavender essential oil (0.1%) reduced the number of marbles buried. Finally, 5% lavender essential oil attenuated the serotonin syndrome induced by 40 mg/kg fluoxetine plus 80 mg/kg 5-hydroxytryptophan.

Conclusions

These results indicate an important role for the serotonergic system in the anxiolytic-like effect of lavender essential oil.     

Neuropharmacological in vivo effects and phytochemical profile of the extract from the aerial parts of Heteropterys brachiata (L.) DC. (Malpighiaceae)

Ethnopharmacological relevance

Heteropterys brachiata is a plant species that has been used in traditional Mexican medicine for the treatment of nervous disorders.

Aim of the study

To evaluate the anxiolytic, anticonvulsant, antidepressant and sedative effects produced by the methanolic extract of Heteropterys brachiata (HbMeOH) in ICR mice. Additionally, we determine the acute toxicity profiles of the extract and the presence of its main constituents.

Material and methods

The neuropharmacological effects of the extract were evaluated using a variety of models, such as the elevated plus maze (EPM), the forced swimming test (FST), the pentobarbital potentiation test (PTBt), pentylenetetrazole-induced seizures test (PTZt), and the open field test (OFT). HPLC was employed for obtention of phytochemical profile.

Results

HbMeOH produced a significant antidepressant effect in FST at 500 and 750 mg/kg doses, while doses from 500 to 1500 mg/kg exhibited a clear dose-dependent anxiolytic activity in EPM. A dose of 500 mg/kg showed a significant anticonvulsant activity in PTZt and an absence of sedation effects in PTBt. The main compounds of HbMeOH were chlorogenic acid and chlorogenic acid methyl ester, as well as less abundant terpene-type compounds. Furthermore, the extract was either safe with no deaths in mice treated orally with 2000 mg/kg.

Conclusions

HbMeOH extract which contains mainly hydroxycinnamic acids and triterpene-type compounds, possesses antidepressant, anxiolytic and anticonvulsive properties and can be considered safe or of low toxicity when orally administrated. These findings lend pharmacological justification to the traditional use of Heteropterys brachiata in the treatment of nervous disorders.     

Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina

Ethnopharmacological relevance

Hemerocallis citrina, a traditional herbal medicine, has been used for the improvement of emotions in Eastern-Asia countries.

Aim of the study

Herein, we explored the antidepressant-like effect and its monoaminergic mechanism of the ethanol extracts from Hemerocallis citrina (HCE).

Materials and methods

Effect of HCE (90, 180 and 360 mg/kg, p.o.) on the immobility time was assessed in the mouse forced swim test (FST) and tail suspension test (TST), and locomotor activity was evaluated in the open-field test (OFT). Additionally, the monoamine neurotransmitters serotonin (5-HT), noradrenaline (NA) and dopamine (DA) levels involved in the antidepressant-like effect of HCE were also measured in the mice brain regions of frontal cortex and hippocampus.

Results

HCE (90, 180 and 360 mg/kg, p.o.) administration significantly reduced the immobility time in both the FST and TST without accompanying changes in locomotor activity in the OFT. The pretreatment of mice with WAY 100635 (0.1 mg/kg, s.c., a 5-HT_1A receptor antagonist), cyproheptadine (3 mg/kg, i.p., a 5-HT₂ receptor antagonist), prazosin (62.5 μg/kg, i.p., an α₁-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α₂-adrenoceptor antagonist), propranolol (5 mg/kg, i.p., a β-adrenoceptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D₂ receptor antagonist), but not SCH23390 (0.05 mg/kg, s.c., a dopamine D₁ receptor antagonist) prevented the antidepressant-like effect of HCE (360 mg/kg, p.o.) in the TST. In addition, HCE enhanced 5-HT and NA levels in the frontal cortex and hippocampus as well as elevated DA levels in the frontal cortex.

Conclusion

The results indicate that the antidepressant-like effect of HCE is dependent on the serotonergic (5-HT_1A and 5-HT₂ receptors), noradrenergic (α₁-, α₂- and β-adrenoceptors) and dopaminergic (D₂ receptor) systems as well as the elevation of 5-HT, NA and DA levels in the mouse brain.     

Anxiolytic effects of yokukansan, a traditional Japanese medicine, via serotonin 5-HT(1A) receptors on anxiety-related behaviors in rats experienced aversive stress

Ethnopharmacological relevance

Yokukansan, a traditional Japanese medicine (Kampo), has been reported in the treatment of behavioral and psychological symptoms of dementia (BPSD) such as aggression, anxiety and depression in patients with Alzheimer’s disease and other forms of senile dementia.

Aims of the study

In the present study, we investigated the anxiolytic effects of yokukansan on anxiety-related behaviors in rats that have experienced aversive stress.

Materials and methods

We used male Wistar/ST rats which received an electrical footshock as aversive stress. Yokukansan at a dose of 1.0 g/kg was administered orally once a day for 14 or 16 day before behavioral tests. To evaluate the anxiolytic effects, we used the contextual fear conditioning (CFC) test and elevated plus-maze (EPM) test. And we also investigated effects of yokukansan on locomotor activity in the Open-field (OF) test and on the change in plasma corticosterone after CFC stress, in rats that had experienced footshock stress.

Results

In the CFC test, rats that had experienced footshock showed significant freezing behavior on re-exposure to the box 14 day after footshock stress. Yokukansan significantly suppressed freezing behavior in the CFC test. In the EPM test on the 16th day after the CFC test, yokukansan significantly increased the time spent in open arms after footshock stress compared to control rats. However, repeated administration of yokukansan on the 14th day did not affect the decrease in locomotor activity and the increase in plasma corticosterone by re-exposure to the box 14 day after footshock stress in the OF test and determination of serum corticosterone, respectively. These anxiolytic effects by yokukansan were antagonized by WAY-100635, a selective 5-HT_1A receptor antagonist, in the CFC test, but not the EPM test. Furthermore, 5-HT_1A receptor agonist buspirone significantly suppressed freezing behavior in the CFC test; however, buspirone induced no change in the time spent in open arms in the EPM test.

Conclusion

These findings suggested that yokukansan has anxiolytic effects on anxiety-like behaviors induced by both innate fear and memory-dependent fear. In particular, yokukansan produced anxiolytic effects via 5-HT_1A receptors in memory-dependent fear induced by aversive stress. Furthermore, yokukansan could be useful as one of the therapeutic drugs for the treatment of anxiety disorders and various mental disorders that have comorbid anxiety.     

Horse chestnut extract contracts bovine vessels and affects human platelet aggregation through 5‐HT2A receptors: an in vitro study

Extract from seeds and bark of horse chestnut (Aesculus hippocastanum L) is used as an herbal medicine against chronic venous insufficiency. The effect and mechanism of action on veins, arteries, and platelets are not fully understood. The aim of this study was to investigate the effects and mechanisms of action of horse chestnut on the contraction of bovine mesenteric veins and arteries, and human platelet aggregation. Contraction studies showed that horse chestnut extract dose‐dependently contracted both veins and arteries, with the veins being the most sensitive. Contraction of both veins and arteries were significantly inhibited by the 5‐HT_2A receptor antagonist ketanserin. No effect on contraction was seen with the cyclooxygenase inhibitor indomethacin, the α₁ receptor antagonist prazosin or the angiotensin AT₁ receptor antagonist saralasin neither in veins nor arteries. ADP‐induced human platelet aggregation was significantly reduced by horse chestnut. A further reduction was seen with the extract in the presence of ketanserin. In conclusion, horse chestnut contraction of both veins and arteries is, at least partly, mediated through 5‐HT_2A receptors. Human platelet aggregation is reduced by horse chestnut. The clinical importance of these findings concerning clinical use, possible adverse effects, and drug interactions remains to be investigated. Copyright © 2010 John Wiley & Sons, Ltd.     

Postnatal development and reproductive performance of F1 progeny exposed in utero to an ayurvedic contraceptive: Pippaliyadi yoga

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from the leaves of Apocynum venetum (AV) using the elevated plus maze (EPM) in mice. Male C75BL/6 mice were either treated orally with the AV extract or the positive controls diazepam and buspirone, respectively, 1 h before behavioral evaluation in the EPM. A single treatment of AV extract markedly increased the percentage time spent on and the number of entries into the open arms of the EPM in doses of 30 and 125 mg/kg p.o., respectively. This effect was comparable to that of the benzodiazepine diazepam (1.5 mg/kg p.o.) and the 5-HT_1A agonist buspirone (10 mg/kg p.o.). The effects of AV in 125 mg/kg were effectively antagonized by the benzodiazepine antagonist flumazenil (3 mg/kg i.p.). However, the effects of AV extract could only partially be blocked by the unspecific 5-HT_1A receptor antagonist WAY-100635 (0.5 mg/kg i.p.). Neither diazepam and buspirone nor the AV extract produced any overt behavioral change or motor dysfunction in the open field test. These results indicate that AV extract is an effective anxiolytic agent, and suggest that the anxiolytic-like activities of this plant are mainly mediated via the GABAergic system.     

Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (P<0.05). However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus saline controls. In the hole-board test, repeated treatment with the aqueous extract of Uncaria rhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (P<0.05). In addition, the anxiolytic-like effects of Uncaria rhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.     

Citrus essential oils inhalation by mice: Behavioral testing,GCMS plasma analysis,corticosterone, and melatonin levels evaluation

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex? immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic‐like, sedative, and antidepressant‐like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic‐like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels.     

Central Nervous System Activities of Hypericum origanifolium Extract via GABAergic and Opioidergic Mechanisms

Pharmacological effects of hydroalcoholic extract prepared from Hypericum origanifolium Willd. (Guttiferae) on behavioral parameters and pain perceptions of mice were investigated in this study. Depression, anxiety, spontaneous locomotor activity, and motor coordination parameters of mice were assessed by modified forced swimming, hole board, activity cage, and rota‐rod tests, respectively. In addition, antinociceptive effect was evaluated by performing hot‐plate, tail‐clip, and formalin tests. Reboxetine (20 mg/kg), diazepam (1 mg/kg), and morphine (10 mg/kg) were used as reference antidepressant, anxiolytic, and analgesic drugs, respectively. Phytochemical analyses exhibited that chlorogenic acid (2317.12 ppm) and rutin (2108.79 ppm) were the main phenolic compounds in the H. origanifolium extract. The extract (50, 100, and 250 mg/kg) induced significant antidepressant, anxiolytic, and antinociceptive activities following the acute administrations. Anxiolytic effect was antagonized by flumazenil (a benzodiazepine receptor antagonist, 2.5 mg/kg, i.p.) pre‐treatment, which indicated the participation of GABA(A)‐benzodiazepine receptor complex in the activity. Moreover, centrally and peripherally mediated antinociception reversed by naloxone (a non‐selective opioid receptor antagonist, 5 mg/kg, i.p.) pre‐treatment, indicating the involvement of opioid system in the pharmacological action. These findings are the first to indicate the pharmacological effects of the H. origanifolium extract on the emotional state and pain perceptions of mice. Copyright © 2012 John Wiley & Sons, Ltd.     

Anti-stress effect of astragaloside IV in immobilized mice

Ethnopharmacological relevance

Astragaloside IV, a major component extracted from the roots of Astragalus membranaceus (AM), possesses anti-inflammatory, anti-oxidative, anti-fibrotic, anti-infarction and immunoregulatory effects. To clarify anti-stress effect of AM, anxiolytic and anti-inflammatory effects of 80% ethanol extract of AM and astragaloside IV were investigated in immobilization stress model.

Materials and methods

The mice were orally administered with AM (50, 200, and 500 mg/kg), astragaloside IV (5, 10, and 20 mg/kg) and buspirone, a positive drug, 1 h before immobilization treated for 2 h. For anxiolytic activity assay, EPM test was performed in mice. For anti-inflammatory activity assay, serum levels of corticosterone, IL-6 and TNF-α were measured using ELISA kits.

Results

AM extract and astragaloside IV increased dose-dependently time spent on open arms and open arm entries in the EPM test. Anxiolytic effects of AM extract (500 mg/kg) and astragaloside IV (20 mg/kg) were comparable to those of buspirone (1 mg/kg). Their anxiolytic effects were blocked by WAY-100635 (0.5 mg/kg, i.p.), a 5-HT_1A receptor antagonist (p<0.01), but not by flumazenil (3 mg/kg, i.p.) and bicuculline (0.5 mg/kg, i.p.), GABA_A receptor antagonists. AM extract and astragaloside IV also reduced serum levels of corticosterone, IL-6 and TNF-α dose-dependently.

Conclusions

AM, particularly astragaloside IV, may ameliorate immobilized stress-induced anxiety and inflammation.     

牡丹皮中丹皮酚的抗焦虑作用

目的:探讨中药牡丹皮抗焦虑作用物质基础.方法:80只成年雄性昆明种小鼠随机分为空白组(Control),阳性药组(地西泮,BZ,1 mg·kg-1),牡丹皮水蒸气蒸馏馏分低、中、高剂量组(Px,50,100,200 mg· kg-1),牡丹皮蒸馏剩余药渣水提物低、中、高剂量组(Wx,100,200,400 mg· kg-1);实验依次进行自由探索模型实验(FEP)、旷场实验(OFT)、高架十字迷宫实验(EPM)、高架○迷宫实验(EZM)和明暗箱实验(LDB);FEP实验参数包括陌生区时间百分率(Ntime％)、陌生区水平运动百分率(Ncross％)、陌生区垂直运动百分率(Nrear％)、总水平运动(Cross)和总垂直运动(Rear);OFT实验参数包括中央区时间百分率(Ctime％)、中央区水平运动百分率(Ccross％)、总水平运动(Cross)和总垂直运动(Rear);EPM和EZM实验参数包括开臂时间百分率(Otime％)、开臂进入次数百分率(Oentries％)和两臂总进入次数(Entries);LDB实验参数包括明区停留时间百分率(Ltime％)、明区水平运动百分率(Lcross％)、明区垂直运动百分率(Lrear％)、穿梭次数(Transition)、总水平运动(Cross)和总垂直运动(Rear).结果:与Control组比较,BZ及Px低、中、高剂量可显著增加FEP_Ntime％,FEP_Ncross％,FEP_Nrear％,OFT_Ctime％,OFT_ Ccross％,EPM_Otime％,EPM_Oentries％,EZM_Otime％,EZM_Oentries％,LDB_ Ltime％,LDB_Lcross％,LDB_Lrear％(P＜0.05);Wx仅高剂量可显著增加OFT_Ccross％,EZM_Otime％,LDB_Lrear(P＜0.05);BZ及Px,Wx低、中、高剂量对FEP_Cross,FEP_Rear,OFT_Cross,OFT_Rear,EPM/EZM_Entries,LDB_Transition,LDB_Cross,LDB_Rear实验参数影响均无统计学差异.结论:牡丹皮抗焦虑作用有效部位是水蒸气蒸馏馏分(Px),即丹皮酚类成分,其可能的作用靶点是γ-氨基丁酸A受体(GABAAR).     

Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae)

An aqueous alcohol extract of Eschscholzia californica (Ec) has been evaluated for benzodiazepine, neuroleptic, antidepressant, antihistaminic and analgesic properties, in order to complete the study of the sedative and anxiolytic effects previously demonstrated. The plant extract did not protect mice against the convulsant effects of pentylenetetrazol, and did not cause muscle relaxant effects but appeared to possess an affinity for the benzodiazepine receptor: thus, flumazenil, an antagonist of these receptors, suppressed the sedative and anxiolytic effects of the extract. The Ec extract induced peripheral analgesic effects in mice but did not possess antidepressant, neuroleptic or antihistaminic effects.     

Evidence of the involvement of the monoaminergic systems in the antidepressant-like effect of Aloysia gratissima

Ethnopharmacological relevance

Aloysia gratissima (Verbenaceae) is an aromatic plant distributed in South America and, employed in folk medicine for the treatment of nervous systems illness, including depression. The neuroprotective and antidepressant-like activities of the aqueous extract of Aloysia gratissima (AE) administered orally has already been demonstrated.In this study the involvement of monoaminergic systems in the antidepressant-like effect of the AE was investigated.

Materials and methods

The implication of the monoaminergic systems in the antidepressant-like activity of Aloysia gratissima was evaluated using different pharmacological antagonists that were administered previously to the acute oral administration of AE (10 mg/kg). The antidepressant-like effect was assessed in the TST and locomotor activity was evaluated in the open-field test in mice.

Results

The anti‐immobility effect elicited by AE in the TST was prevented by the pre-treatment of mice with the antagonists, NAN‐190 (5‐HT_1A receptor), ketanserin (5‐HT_2A/2C receptor), prazosin (α₁‐adrenoceptor), yohimbine (α₂‐adrenoceptor), SCH23390 (dopamine D₁ receptor), or sulpiride (dopamine D₂ receptor).

Conclusions

These results indicate that the antidepressant‐like effect of AE in the TST is dependent on its interaction with the serotonergic (5‐HT_1A and 5‐HT_2A/2C), noradrenergic (α₁ and α₂₋adrenoceptors) and dopaminergic (D₁ and D₂ receptors) systems, suggesting that this specie might act as a new potential resource for developing antidepressants to treat depressive disorders.     

Central nervous system activity of the hydroalcoholic extract of Casimiroa edulis in rats and mice

In order to evaluate the effects produced by the hydroalcoholic extract of leaves from Casimiroa edulis on the central nervous system, different behavioral tests and animal models of depression and anxiety were performed. The extract was administered intraperitoneally in male and female rats and tested on spontaneous motor activity, locomotor activity, exploration of an elevated plus-maze (EPM) and in the forced swimming test (FST). In addition, the extract was administered orally in male and female mice and evaluated in the following tests: general observation, pentobarbital-induced hypnosis, EPM, rota-rod, hole-board, and marble-burying. The results revealed that, in rats, the extract caused considerable reduction of locomotor and exploratory activities and increased the exploration of the EPM open arms in a similar way that diazepam. In the FST, the extract was as effective as fluoxetine in inducing shortening of immobility, along with a significant increase on climbing duration. On the other hand, in mice, the extract prolonged pentobarbital-induced hypnosis, increased exploration of the EPM open arms and partially protected from the pentylenetetrazol-induced convulsions. No significant effect was evident on motor coordination, hole-board and marble-burying tests. These results suggest that the hydroalcoholic extract of Casimiroa edulis may contain sedative principles with potential anxiolytic and antidepressant properties, which need further investigation.     

虎杖水提和乙醇提取物抗抑郁作用的比较

目的:考查虎杖水提物(HZ-W)和虎杖75％乙醇提取物(醇提物,HZ-E)的抗抑郁作用.方法:雄性昆明种小鼠随机分为模型组、盐酸氟西汀(FH,10 mg ·kg-1)、HZ-W(1.5,3 g·kg-1)和HZ-E(1.5,3 g·kg-1)组,连续灌胃(ig)给药7d,1次/d,末次给药后1h,进行悬尾实验(TST)、强迫游泳实验(FST)和开场实验(OFT)测试.结果:模型组小鼠TST和FST不动时间分别为(95.83±17.18),(126.00±20.79)s,HZ-W低剂量和高剂量、HZ-E高剂量以及FH均显著缩短了不动时间(P＜0.05),而HZ-E低剂量对此无显著影响.OFT中,模型组小鼠3 min内穿格次数为(88.44±19.22)次,各给药组与之相比均无显著差异.结论:首次证实HZ-W和HZ-E均具有抗抑郁活性,且以HZ-W作用更强.     

Effect of lyophilized extracts from guaraná seeds [Paullinia cupana var. sorbilis (Mart.) Ducke] on behavioral profiles in rats

The aim of the present study was to investigate the pharmacological properties of the crude lyophilized extract (EBPC) of Paullinia cupana seeds (guaraná) and the semi-purified extracts (EPA and EPB) after acute or chronic administration by the oral route in rats. Anxiolytic-like, antidepressant-like and motor stimulant effects were evaluated using the plus maze (PMT), forced swimming (FST) and open field (OFT) tests, respectively. Acute or chronic administration of EBPC (3.0, 30.0 or 60.0 mg/kg) did not alter the percentage of entries or the time spent in the open arm in the PMT. In the FST, chronic treatment with 30.0 mg EBPC/kg and 4.0 mg EPA/kg extract decreased the immobility time similarly to the antidepressant reference drug, imipramine (20.0 mg/kg). Locomotor activity in the OFT was not increased by these extracts. Caffeine (10.0 mg/kg) significantly reduced the immobility time in the FST, but increased locomotor activity in the OFT, indicating psychostimulant activity. The EPB extract did not induce any effect after acute or chronic treatment in the different models used. The present results suggest that the crude EBPC extract and EPA extract produced an antidepressant-like effect after long-term administration.     

半夏泻心汤抗抑郁作用实验研究

目的:探讨中药经方半夏泻心汤(BXT)抗抑郁作用.方法:补给药途径、天数及与检测的时间关系120只成年雄性昆明种小鼠随机分为空白组(Control;n=24),阳性药氟西汀组(FLU,10 mg·kg-1,ig,n=24),BXT低、中、高剂量组(50,100,200 mg· kg-1;n=24),分别进行旷场实验(open field test,OFT;n =8)、悬尾实验(tail suspension test,TST;n =8)和强迫游泳实验(forced swimming test,FST;n=8);OFT实验参数包括水平运动得分、垂直运动得分和总得分,TST和FST实验参数是不动状态持续时间.结果:OFT结果提示,与Control比较,FLU和BXT低、中、高剂量对OFT水平运动得分、垂直运动得分及总得分影响差异均无统计学意义;TST结果提示,与Control比较,FLU和BXT低、中、高剂量可明显缩短TST不动状态持续时间(P＜0.01,P＜0.05,P＜0.01,P＜0.01);FST结果提示,与Control比较,FLU和BXT低、中、高剂量可明显缩短FST不动状态持续时间(P＜0.01,P＜0.05,P＜0.01,P＜0.01).结论:半夏泻心汤具有明显抗抑郁作用,但其具体作用机制尚未明确.     

Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats

Aim of the study

The purpose of the present study was to screen aromatic essential oils that have antidepressant effects to identify the regulatory mechanisms of selected essential oils.

Materials and methods

The antidepressant effects of essential oils of Anthemis nobilis (chamomile), Salvia sclarea (clary sage; clary), Rosmarinus officinalis (rosemary), and Lavandula angustifolia (lavender) were assessed using a forced swim test (FST) in rats. Rats were treated with essential oils by intraperitoneal injection or inhalation. Serum levels of corticosterone were assessed by enzyme-linked immunosorbent assay (ELISA).

Results

Among the essential oils tested, 5% (v/v) clary oil had the strongest anti-stressor effect in the FST. We further investigated the mechanism of clary oil antidepression by pretreatment with agonists or antagonists to serotonin (5-HT), dopamine (DA), adrenaline, and GABA receptors. The anti-stressor effect of clary oil was significantly blocked by pretreatment with buspirone (a 5-HT_1A agonist), SCH-23390 (a D₁ receptor antagonist) and haloperidol (a D₂, D₃, and D₄ receptor antagonist).

Conclusions

Our findings indicate that clary oil could be developed as a therapeutic agent for patients with depression and that the antidepressant-like effect of clary oil is closely associated with modulation of the DAnergic pathway.     

Bioassay‐guided isolation of apigenin with GABA‐benzodiazepine activity from Tanacetum parthenium

Extracts of Tanacetum parthenium are used in the prophylactic treatment of migraine and have also been used in Danish folk medicine for the treatment of epilepsy. An ethanol extract of T. parthenium showed high affinity for the GABA_A‐benzodiazepine site. An ethanol extract of T. parthenium was fractionated by VLC on silica and preparative C18 HPLC. Each step was monitored with the GABA_A‐benzodiazepine bioassay. The fractionation led to the isolation of apigenin, which may be responsible for CNS‐effects of T. parthenium extracts. Copyright © 2009 John Wiley & Sons, Ltd.