Anxiolytic effect of saponins from Panax quinquefolium in mice

The anxiolytic effect of the saponins from Aniliaeea Panax quinquefolium L. (PQS) was studied in male mice by using a number of experimental paradigms of anxiety and compared with that of the known anxiolytic compound diazepam. Use of the elevated plus-maze test revealed that PQS (50 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) increased the percentage of time and entries spent in open arms. In the light/dark test, PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) prolonged the time spent in the light area. In the hole-board test, PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) significantly increased both head-dip counts and head-dip duration. Both PQS (50 and 100 mg/kg, p.o.) and diazepam (2.5 mg/kg, p.o.) decreased the total fighting time in the isolation-induced aggressive test. Since PQS, in contrast to diazepam, had no effect on locomotion in these tests, its side-effect profile might be considered superior to the benzodiazepines. Thus, the present findings suggest that PQS might be a potential candidate for use as an anxiolytic drug.     

The anxiolytic effect of Sho-ju-sen, a Japanese herbal medicine, assessed by an elevated plus-maze test in mice

Sho-ju-sen (SK), a Japanese herbal medicine with a nourishing tonic action, is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) (SS), and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. et Zucc) (PN) and Ginseng roots (Panax ginseng C. A. Meyer) (PX) in the ratio 8:1:1. In this study, an elevated plus-maze test in mice was carried out to assess whether SK had an anxiolytic effect. No significant change was observed in either the plus-maze or activity test following a single administration of SK (10 and 20 mL/kg p.o.). However, mice allowed a free intake of SK (10% solution) for 5 days and longer showed a significant prolongation of the time spent in the open arms (an anxiolytic effect), as long as that caused by the benzodiazepine anxiolytic diazepam (1 mg/kg p.o.). SK (1%, 3% and 30% solutions for 7 days) tended to develop the anxiolytic effect. Of the constituents of SK, SS (8% solution), but not PN (1% solution) or PX (1% solution), resulted in the anxiolytic effect. Except for a slight acceleration in the motor activity by PN (1% solution), no significant change in the motor activity was produced by any treatment with SK, SS or PX. The combined treatment of SK (10% solution) or SS (8% solution) with 1 mg/kg diazepam enhanced the anxiolytic effect. Flumazenil (0.1 mg/kg s.c.), a benzodiazepine receptor antagonist, alone did not change the time spent in the open arms. However, it completely reversed the anxiolytic effect of SK, SS and diazepam. The present results suggest that: (1) long-term treatment with SK develops an anxiolytic effect, (2) SS is the main constituent for the anxiolytic effect of SK, and (3) benzodiazepine receptors are involved in the anxiolytic effect of SK and SS.     

Anxiolytic‐like effects of standardized extract of Justicia pectoralis (SEJP) in mice: Involvement of GABA/benzodiazepine in receptor

Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic‐like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic‐like effect, disproving sedative effects. Copyright © 2010 John Wiley & Sons, Ltd.     

Effects of Methyl and Isopropyl N‐methylanthranilates from Choisya ternata Kunth (Rutaceae) on Experimental Anxiety and Depression in Mice

Choisya ternata Kunth (Rutaceae) is a plant species used in Mexican folk medicine for its antispasmodic and simulative properties. Recently, we identified a new alkaloid, isopropyl N‐methylanthranilate, and a related one, methyl N‐methylanthranilate, from the essential oil of this species and have proven them to possess antinociceptive activity even at 0.3 mg/kg. In the present study, anxiolytic and antidepressant effects of the two compounds have been studied in open field, horizontal wire, light/dark, forced swimming and tail suspension tests, as well as the effect on the onset and duration of diazepam‐induced sleep in BALB/c mice. The volatile alkaloids (50–200 mg/kg, administered intraperitoneally), without having a muscle relaxant effect, caused a significant increase in the time the animals spent in an unsecured and putatively dangerous area when compared with the control group but had no effect on the number of crossings between the light/dark compartments. In addition to this anxiolytic activity, a significantly antidepressant‐like effect was apparent at all tested doses, which was not due to an increase in locomotive activity. The anthranilates administered on their own did not induce sleep in mice but significantly prolonged the diazepam‐induced sleep, in a dose‐dependent way, suggesting an interaction with the gamma‐aminobutyric acid receptor complex. Copyright © 2012 John Wiley & Sons, Ltd.     

Possible anxiolytic effect of two extracts of Passiflora quadrangularis L. in experimental models

Several species of the genus Passiflora, known in Brazil as 'maracujá', have widespread use in folk medicine as sedatives and anxiolytics. The anxiolytic activities of aqueous and hydroalcohol extracts of Passiflora quadrangularis leaves were evaluated using the elevated plus-maze, open field and holeboard tests. The hydroalcohol extract presented results suggestive of anxiolytic activity in dosages around 100, 250 and 500 mg/kg, as expressed by elevation of the time spent on the open arms in the plus-maze; a decrease of freezing and an increase of deambulation and rearing in the open field test. The hydroalcohol extract showed results similar to diazepam on the holeboard. No positive results were found for the aqueous extract.     

The nitrergic neurotransmission contributes to the anxiolytic‐like effect of Citrus sinensis essential oil in animal models

Citrus fragrances have been used in aromatherapy for the treatment of anxiety, and the essential oil of Citrus sinensis (sweet orange) has shown promising results, although its mechanism of action was not known. The objective of this study was to evaluate the involvement of nitric oxide (NO) neurotransmission in the anxiolytic‐like effect of C. sinensis essential oil. Swiss male mice were submitted to 15 min of C. sinensis essential oil inhalation (1%, 2.5%, 5%, and 10%) and tested in the marble‐burying test, neophobia‐induced hypophagia, and light/dark test. Locomotor activity was evaluated in an automated locomotor activity box. The coadministration of C. sinensis essential oil with L‐arginine (200 mg/kg, i.p.), an NO precursor, was used for the behavioral evaluation of nitrergic system mediation. Additionally, the NO synthase activity was measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) analysis in the cerebral cortex. C. sinensis essential oil exerted anxiolytic‐like effect at dose that did not change locomotor activity. Moreover, L‐arginine pretreatment prevented this anxiolytic‐like effect on marble‐burying test. Finally, C. sinensis essential oil reduced the NADPH‐d positive cells. Thus, the nitrergic neurotransmission plays a relevant role in the anxiolytic‐like effect C. sinensis essential oil.     

Dominant lethal study of α‐asarone in male and female mice after sub‐chronic treatment

Dominant lethal studies were conducted in male and female mice with α‐asarone, the active hypolipidaemic component of Guatteria gaumeri Greenman, by per os sub‐chronic treatment (10 and 20 mg/kg, 5 days/week, for 8 weeks) and subsequent mating. α‐Asarone did not produce germinal mutations in either males or females. Epididymal sperm examination of male mice immediately after treatment failed to­reveal any alteration in sperm count on shape. No significant alterations were observed in testicular or epididymal weights or testicular histology. Copyright © 1999 John Wiley & Sons, Ltd.     

Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL

The sedative, anxiolytic and muscle-relaxant effects of the ethyl acetate leaf extract of Baphia nitida (BN) was investigated in intact mice, using the hole-board head-dip test for exploratory behavioural effect, elevated plus maze (EPM) and Y-maze (YM) models of anxiety; chimney, inclined screen, traction and climbing tests for muscle-relaxant effects. In each of these tests, BN (100-400mg/kg, p.o.), diazepam (1mg/kg, i.p.) or distilled water (10ml/kg, p.o.) was administered, 30 or 60min before performing the tests in mice. For exploratory behavioural test, number of head-dip within 15min was counted. For EPM and YM tests, the cumulative time spent in open and closed arms was recorded within 5min. In the muscle-relaxant tests, mice were subjected to modified models such as chimney, inclined screen, traction and climbing tests. BN produced a significant (P<0.05) dose-related decrease in exploratory behaviour in the head-dip test and prolongation of cumulative time spent in open arms of both EPM and YM. BN did not show any significant effect in the chimney and traction tests, but produced significant, dose-dependent muscle relaxation in the inclined screen and climbing tests. Furthermore, BN (200-1200microg/ml) non-competitively shifted the curves of acetylcholine contractions of the toad Rectus abdominis muscle to the right. Oral doses of BN (0.1-20g/kg) did not produce mortality, but the LD(50) when given intraperitoneally, was 645.65mg/kg. Results suggest that the leaf extract of Baphia nitida has sedative, anxiolytic and skeletal muscle-relaxant effects and support its neurosedative use in traditional African medicine.     

Anxiolytic effects of Salvia reuterana Boiss. on the elevated plus-maze model of anxiety in mice

The anxiolytic and sedative effects of hydroalcoholic extract (HE) of Salvia reuterana Boiss. was evaluated in mice. The HE of Salvia reuterana (100 mg/kg), increased the percentage of time-spent and the percentage of arm entries in the open arms of the elevated plus-maze. Spontaneous locomotor activity count measured in 15 min of the test was significantly decreased in animals pretreated with diazepam and 100 mg/kg of Salvia reuterana extract. Results of the present study provide support for the traditional usage of Salvia reuterana as a sedative and anxiolytic medicinal plant.     

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.     

Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats

Bergamot essential oil (BEO), Citrus aurantium subsp. bergamia (Risso) Wright & Arn. (Rutaceae), is used widely in aromatherapy to reduce stress and anxiety despite limited scientific evidence. A previous study showed that BEO significantly increased gamma-aminobutyric acid levels in rat hippocampus, suggesting potential anxiolytic properties. The aim of this study was to investigate the effect of BEO (1.0%, 2.5% and 5.0% w/w) administered to rats on both anxiety-related behaviours (the elevated plus-maze (EPM) and hole-board tests) and stress-induced levels of plasma corticosterone in comparison with the effects of diazepam. Inhalation of BEO (1% and 2.5%) and injection of diazepam (1 mg/kg, i.p.) significantly increased the percentage of open arm entries on the EPM. The percentage time spent in the open arms was also significantly enhanced following administration of either BEO (2.5% and 5%) or diazepam. Total arm entries were significantly increased with the highest dose (5%), suggesting an increase in locomotor activity. In the hole-board test, 2.5% BEO and diazepam significantly increased the number of head dips. 2.5% BEO and diazepam attenuated the corticosterone response to acute stress caused by exposure to the EPM. In conclusion, both BEO and diazepam exhibited anxiolytic-like behaviours and attenuated HPA axis activity by reducing the corticosterone response to stress.     

Expression of BDNF and TH mRNA in the Brain Following Inhaled Administration of α‐Pinene

Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.     

Hydroalcohol extract and fractions of Stachys lavandulifolia Vahl: effects on spontaneous motor activity and elevated plus-maze behaviour

The present study aimed to investigate the anxiolytic effects of four fractions of Stachys lavandulifolia Vahl. The aerial parts of the plant were extracted with petroleum ether (PF), ethyl acetate (EF), butanol (BF) and water (AF) and tested for spontaneous motor activity and elevated plus-maze (EPM) behaviour in mice. The hydroalcohol extract (HE) and different fractions of S. lavandulifolia were administered intraperitoneally to male Syrian mice, at various doses, 30 min before the behavioural evaluation. The HE of S. lavandulifolia (at 50 mg/kg) increased the percentage of time spent (39%) and the percentage of arm entries in the open arms (53%). The HE (50 mg/kg), PF (25 and 50 mg/kg), EF (25 and 50 mg/kg) and AF (50 mg/kg) of S. lavandulifolia significantly increased the percentage of time spent and the percentage of arm entries in the open arms. The BF up to a dose of 50 mg/kg had no significant effects on any of the measured parameters in the EPM. The spontaneous locomotor activity was significantly decreased in animals injected with each plant fractions, compared with that of saline. The EF and AF showed the least and the most reduction in the activity, respectively. The anxiolytic effects of EF, PF and AF could be related to their content of flavonoids, phenylpropanoids or terpenoids.     

Daily Inhalation of α‐Pinene in Mice: Effects on Behavior and Organ Accumulation

In phytotherapy, essential oils tend to be used daily for a period of days or weeks, rather than in a single application. However, the literature contains very little information on repeated use of essential oils. In this study, we investigated the effects on behavior and the accumulation in the brain and liver of α‐pinene, an essential oil component, when inhaled by mice. Animals were individually housed in cages for 1 week. Mice inhaled α‐pinene or water vapor (negative control) for 90 min/day for 1 day, 3 days, or 5 days, and they were then submitted to the elevated plus maze test for 10 min. We used gas chromatography with flame ionization detection to quantify concentrations of α‐pinene in the brain and liver. There was significant anxiolytic‐like activity, which remained constant for the 5 days' inhalation of α‐pinene. On the other hand, the accumulation of α‐pinene in the brain and liver peaked on the third day of inhalation. The existence of stress related to the new environment appears to have affected the change in the accumulation of α‐pinene in the internal organs, keeping the anxiolytic‐like action constant. Copyright © 2013 John Wiley & Sons, Ltd.     

Anxiolytic effect of ting-chih-wan in mouse behavior models of anxiety

The anxiolytic effect of the alcoholic extract of ting-chih-wan (TCWa) was studied using the black and white test (BWT) and the elevated plus-maze (EPM). We further demonstrated the anxiolytic mechanism of TCWa by combining with diazepam (DIZ), serotonin (5-HT) agonists or antagonists, and measuring the levels of monoamines and its metabolites in the brain stem and cortex. In the BWT, TCWa (0.1-1.0 g/kg, p.o.) increased the time spent in the white chamber and total change between the two chambers, and decreased the time spent in the black chamber. TCWa (0.1-0.5 g/kg, p.o.) increased the arm entries and the time spent on the open arms, and decreased the arm entries and the time spent on the closed arms in the EPM. On the other hand, TCWa (1.0 g/kg, p.o.) decreased horizontal activity and prolonged pentobarbital-induced sleeping times. TCWa (0.1, 0.5 g/kg) decreased the levels of norepinephrine (NE), dopamine (DA), 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) and increased the levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in the brain stem. TCWa (0.1 and 0.5 g/kg) decreased the levels of NE, DA and increased the levels of VMA and HVA in the cortex. TCWa also attenuated the anxiogenic effect of 5-hydroxytryptophan (5-HTP) and enhanced the anxiolytic effect of 9p-chlorophenylalanine (PCPA), buspirone (BUS) and ritanserin (RIT) in the EPM. From these results, TCWa at 0.1 and 0.5 g/kg possessed an anxiolytic effect T heanxiolytic mechanisms of TCWa might be due to decreased catecholaminergic activity caused by the increase in the turnover rate of catecholamines in the brain and decreased concentrations of 5-HT in the brain stemvia activating somatodendritic 5-HT1A autoreceptors and inhibiting postsynaptic 5-HT receptors.     

Flavonoids from Tilia americana with anxiolytic activity in plus-maze test

The aerial parts of Tilia americana var. mexicana (Schltdl) Hardin (Tiliaceae) have been widely used in Mexican traditional medicine to relieve sleeplessness, headache, and nervous excitement. The anxiolytic effect of four extracts and several flavonoid fractions from the bracts of Tilia americana subsp.mexicana, var. mexicana (Schltdl) Hardin or Tilia mexicana (Tiliaceae) was studied. Administration of 100mg/kg of n-hexane, ethyl acetate, and aqueous extracts to elevated plus-maze (EPM)-exposed mice displayed no anxiolytic effect; however, identical doses of methanol extract was able to increase the time percentage that mice spent in the EPM's open arms, as well as the percentage of crossings in the EPM's arms. The dose-response curve produced by methanol extract showed anxiolytic activity since 25mg/kg; animals showed no motor activity alteration in the open field test (OFT). Methanol extract was subjected to a bioassay-guided fractionation to obtain four ascendant polarity fractions (F1-F4) which were administrated at 100mg/kg. Data results indicate that F1 displayed the main anxiolytic effect. The purification of F1 produced a rich flavonoid anxiolytic mixture (F1C). This fraction was purified by RP-18 open chromatographic column to obtain four polar descent fractions: F1C(1), F1C(2), F1C(3), and F1C(4), respectively. Tiliroside was the major ingredient from the active fraction. High performance liquid chromatography analysis indicated that F1C was constituted principally of tiliroside, quercetin, quercitrin, kaempherol, and their glycosides. These results supported the use of Tilia americana in Mexican traditional medicine as well as the anxiolytic effect of a rich flavonoid fraction without affect motor activity.     

Anxiolytic effects of Stachys lavandulifolia Vahl on the elevated plus-maze model of anxiety in mice

Interest in alternative medicine and plant-derived medications that affect the "mind" is growing. The aim of the present study was to investigate the effects of a hydroalcoholic extract and essential oil of Stachys lavanduifolia Vahl on the elevated plus-maze (EPM) model of anxiety. The Stachys lavandulifolia extract or its essential oil was administered intraperitoneally to male TO mice, at various doses, 30 min before the behavioral evaluation. The extract of Stachys lavandulifolia at the dose of 100 mg/kg increased the percentage of time spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time spent and the percentage of arm entries in the closed arms of the EPM. The plant extract at doses lower than 100 mg/kg had no significant effects on any of the parameters measured on the EPM. This dose of the plant extract prolonged the ketamine-induced sleeping time, and decreased the locomotor activity in mice. These results suggested that the extract of Stachys lavandulifolia possessed anxiolytic effect with relatively lower sedative activity than diazepam. The essential oil of Stachys lavandulifolia, however, at doses of up to 100 mg/kg did not have any significant effects on the mice behaviour on the EPM.     

Application of the elevated plus-maze test in mice for evaluation of the content of honokiol in water extracts of magnolia.

In our previous study using an improved elevated plus-maze in mice, the oriental herbal medicine Saiboku-to prolonged the time spent in open arms, showing an anxiolytic effect, and the effect was mainly caused by honokiol derived from magnolia. This study was carried out to compare the anxiolytic potentials of honokiol and water extracts of three magnolia samples; two being Kara-koboku (Magnolia officinalis) (KA: from Zhejiang-sheng, China; honokiol 0.25% and magnolol 1.16%, and KB: from Sichuan-sheng, China; honokiol 1.72% and magnolol 1.71%), and one being Wa-koboku (Magnolia obovata) (WA: from Iwate-ken, Japan; honokiol 0.32% and magnolol 0.81%). Seven daily treatments with 0.1-1 mg/kg honokiol, but not 0.2 and 1 mg/kg magnolol, revealed an anxiolytic effect with the peak potential at 0. 2 mg/kg. The anxiolytic potentials of 40 and 80 mg/kg KA, which contained the highest amount of magnolol, were almost equivalent to those of 0.1 and 0.2 mg/kg honokiol, respectively. KB, at 11.6 mg/kg, and 62.5 mg/kg WA resulted in almost the same anxiolytic potential as that of 0.2 mg/kg honokiol. No significant change in the ambulatory activity was produced by any drug treatment. These results suggest that honokiol is the chemical responsible for the anxiolytic effect of the water extract of magnolia and that the other chemicals including magnolol in magnolia scarcely influence the effect of honokiol. It is also considered that the elevated plus-maze test is applicable for evaluation of the content of honokiol in magnolia.     

The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats

Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Putative anxiolytic and antidepressant properties of Salvia elegans were studied in the elevated plus-maze test (EPM) and in the forced swimming test (FST), respectively. Deleterious effects of Salvia elegans on learning and memory were also studied by using active and passive avoidance paradigms. The results revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a significant decrease in total motility, locomotion, rearing and grooming behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the extract induced a reduction of immobility, in a similar way to that of fluoxetine (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the time spent in swimming behavior. Acquisition of active avoidance responses was disrupted by pre-treatment with the extract, but retention of a passive avoidance response was not significantly modified. These results suggest that some of the components of the hydroalcoholic extract of Salvia elegans have psychotropic properties, which deserve further investigation.     

Evaluation of behavioral and pharmacological effects of Hedyosmum brasiliense and isolated sesquiterpene lactones in rodents

Ethnopharmacological relevance

Hedyosmum brasiliense Miq. (Chloranthaceae) is an essential Brazilian species largely found in the Atlantic Forest. It is popularly known as “cidrão” and in folk medicine, this aromatic species is widely used as a calmative/tranquilizer and to treat sleep disorders.

Aim of the study

To examine the neurochemical properties of ethanol extract (EEHb), fractions and compounds of fresh leaves of Hedyosmum brasiliense and the antidepressant effect of the isolated sesquiterpene lactones podoandin and 13-hydroxy-8,9-dehydroshizukanolide.

Materials, methods and results

The effects of EEHb were demonstrated by the open field, elevated-plus-maze, forced swimming, pentobarbital-induced sleeping time, PTZ-induced seizure, and inhibitory avoidance tests. EEHb did not show a protective effect against PTZ-induced convulsions. In the plus-maze test, EEHb (100 mg/kg, i.p.) exhibited an anxiolytic effect through the effective enhancement of the frequency and time spent in the open arms of the maze. Conversely, the time spent and the number of entrances to the closed arms were decreased. All these effects were also completely reversed by pre-treatment with flumazenil (2.5 mg/kg, i.p./a benzodiazepine receptor agonist), similar to the results observed with diazepam used as a positive standard. In this test, the anxiolytic effect of EEHb was also totally blocked by pre-treatment with reserpine (2.0 mg/kg, i.p.), a drug known to induce depletion of biogenic amines. In the forced swimming test, the treatment of EEHb (100 mg/kg, i.p. or 100 mg/kg, p.o.) given in acute and chronic form (10, 50 and 100 mg/kg), produced a decrease in immobility time, similar to that of imipramine (10 mg/kg, i.p.), the positive control. The dichloromethane and hexane fractions (100 mg/kg, p.o.) also produced a decrease in immobility time. In addition, the two isolated compounds tested in a single dose (10 mg/kg, i.p.), the antidepressant effect was observed only with the compound podoandin, which also caused a decrease in immobility time. EEHb (10–100 mg/kg) a dose-dependent manner also caused a decrease in barbiturate sleeping time in mice, and in high doses (100 mg/kg), did not interfere in memory consolidation.

Conclusions

The results suggest that EEHb presents psychopharmacological activities, including anxiolytic, antidepressant, and hypnotic effects.