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.     

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.     

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.     

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.     

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice

The aim of the present work is to demonstrate the putative sedative and anxiolytic-like effects of a hydro-ethanolic extract obtained from the aerial parts of Aloysia polystachya (Verbenaceae) in male mice using several behavioural assays. Groups of male mice orally treated with doses of 1.0, 10.0 and 100.0 mg/kg of the extract did not show any significant alteration of their locomotor activity, body temperature or motor coordination. The same treatment increased the duration of the sleeping time induced by 30.0 mg/kg i.p. of sodium pentobarbital. However, the sleeping time induced by ethyl ether was not modified by the oral administration of the extract, not confirming the putative sedative effect of the plant. The ethanolic extract also significantly increased the percentage of both entries (1.0 and 100.0 mg/kg) and the time spent (10.0 and 100.0 mg/kg) into the open arms of the elevated plus maze (EPM). Nevertheless, the binding of (3)H-flunitrazepam ((3)H-FNZ) to the benzodiazepine binding site (BDZ-bs), in washed crude synaptosomal membranes from rat cerebral cortex, was not affected by the semi-purified components from Aloysia polystachya. These results indicate an anxiolytic-like profile of action for the extract of Aloysia polystachya without sedative side effect, being this activity probably mediated by other mechanism than BDZ-bs modulation at the GABA(A) receptors.     

Possible involvement of GABA A-benzodiazepine receptor in the anxiolytic-like effect induced by Passiflora actinia extracts in mice

Hydroethanol (HE) and methanol (ME) extracts obtained from the leaves of Passiflora actinia Hooker were evaluated for behavioral effects in mice. Single-dose oral administration of HE (300 and 600 mg/kg) or ME (100 and 300 mg/kg) resulted in anxiolytic-like effects in the elevated plus-maze. The anxiolytic-like effects were also seen after the repeated administration of the HE (100 and 300 mg/kg). Flumazenil (10mg/kg, i.p.), a GABA(A)-benzodiazepine receptor antagonist, blocked the effects of ME (300 mg/kg, p.o.) and HE (600 mg/kg). At higher doses, a sedative effect produced by acute administration of HE (600 mg/kg) or ME (300 mg/kg) was indicated by the potentiation of pentobarbital-induced sleep. With regard to memory-disrupting effects of anxiolytics, mice were evaluated by measuring the retest step-down latency 24h after foot-shock in a passive avoidance task. In contrast to diazepam (0.5mg/kg) or piracetam (200mg/kg), ME (30, 100 and 300 mg/kg) or HE (100, 300 and 600 mg/kg) did not influence the step-through latency in the acquisition or retention memory tasks. The present results show an anxiolytic profile for HE and ME of Passiflora actinia. There are also indications of an involvement of GABA(A) system in this effect.     

The aqueous crude extract of Montanoa frutescens produces anxiolytic-like effects similarly to diazepam in Wistar rats: Involvement of GABAA receptor

Ethnopharmacological relevance

Cihuapatli is the Nahuatl name assigned to some medicinal plants grouped in the genus Montanoa, where Montanoa frutescens (Family: Asteraceae, Tribe: Heliantheae) is included. The crude extract from these plants has been used for centuries in the Mexican traditional medicine as a remedy for reproductive impairments and mood disorders. Experimental studies have systematically corroborated the traditional use of cihuapatli on reproductive impairments and sexual motivation, however, the effect on mood and “nervous” disorders, remains to be explored.

Materials and methods

The anxiolytic-like effect of aqueous crude extract of M. frutescens (25, 50 and 75 mg/kg) was investigated in male Wistar rats evaluated in the elevated plus-maze and compared with several doses of diazepam (1, 2 and 4 mg/kg) as a reference anxiolytic drug. Picrotoxin (1 mg/kg), a noncompetitive antagonist of the GABA_A receptor, was used in experimental procedures to evaluate if this receptor could be involved in the anxiolytic-like effects produced by M. frutescens. To discard hypoactivity, hyperactivity, or no changes associated with treatments, which could interfere with the behavioral activity in the elevated plus-maze, rats were subjected to the open field test.

Results

M. frutescens at 50 mg/kg showed anxiolytic-like activity similarly to 2 mg/kg of diazepam, without disrupts in general motor activity. The anxiolytic-like effect of M. frutescens detected in the elevated plus-maze was blocked by picrotoxin, indicating that GABA_A receptors are involved in the modulation of this effect.

Conclusions

The results corroborate the use of M. frutescens in folk Mexican ethnomedicine as a potential anxiolytic agent and suggest that this effect is mediated by the GABA_A receptors. Additionally, some sedative effects with high doses of M. frutescens were detected in the present study.     

Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice

The purpose of this study was to characterize the putative anxiolytic-like activity of fractions prepared from a hydroethanol extract of Passiflora incarnata L. using the elevated plus-maze (EPM) in mice. The fractions were prepared as published recently, yielding a butanol, petroleum ether and chloroform fraction. From the tested fractions, the butanol fraction showed significant increases in the number of open arm entries in the EPM in concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of the original extract. The highest activity was found for the chloroform fraction in doses of 0.17 mg/kg (10.0 ± 1.9, p < 0.001) and 0.34 mg/kg (6.6 ± 0.86; p < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg, respectively. Interestingly, the petroleum ether fraction did not show any effects in the elevated plus maze. A sedative or stimulatory effect of each of the fractions could be excluded, since none of the compounds had an influence on the total distance that the animals covered during the observation period. The results suggest that the active principle of passion flower seems to be in the chloroform fraction and to a lower extent in the butanol fraction.     

Involvement of 5-HT1A in the anxiolytic-like effect of dichloromethane fraction of Pimenta pseudocaryophyllus

Ethnopharmacological relevance

Medicinal applications of Pimenta pseudocaryophyllus infusion as a diuretic and aphrodisiac agent as well as tranquilizer in the form of tea for the treatment of emotional tension in Brazilian folk medicine has been in practice since time immemorial. Despite its popular therapeutic acceptance and claims, there are scanty scientific reports to corroborate its central biological activities.

Aim

To characterize anxiolytic-like effect of the dichloromethane fraction (DF) obtained from ethanolic leaf extract of the Pimenta pseudocaryophyllus and identify mechanisms of action involved while seeking to support its popular use as a soothing agent.

Material and methods

Mice (25–35 g) were treated orally with DF obtained from ethanolic leaf extract of Pimenta pseudocaryophyllus and were submitted to light-dark box (LDB) and elevated plus maze (EPM) tests. Different groups of mice were treated with flumazenil and NAN-190 to identify mechanisms of action involved in the anxiolytic-like effect of DF.

Results

Treatment with DF increased number of transitions and time spent in the light compartment of the LDB while the time spent and numbers of entries in the open arm of the LCE were significantly increased. Pre-treatment of the animal with flumazenil (2 mg/kg, i.p. – competitive antagonist of benzodiazepine site of GABA_A receptor) did not block this effect, thereby excluding participation of benzodiazepine site of the GABA_A receptor. However, anxiolytic-like effect of DF was reversed by pre-treatment with NAN-190 (0.5 mg/kg, i.p. – an antagonist of the 5-HT_1A receptor) thereby suggesting involvement of 5-HT_1A receptor. The thin layer chromatography and high-performance liquid chromatography analysis indicated the predominance of (E)-methyl isoeugenol and oleanolic acid in DF.

Conclusion

These results support the popular use of Pimenta pseudocaryophyllus as a calming agent and suggest the involvement of 5-HT_1A receptor.     

Ethanol extract of Crocus sativus L. Antagonizes the inhibitory action of ethanol on hippocampal long-term potentiation in vivo

The effect of an ethanol extract of Crocus sativus L. (CSE) on the long-term potentiation (LTP) of the evoked potential in the dentate gyrus of the hippocampus was investigated using anaesthetized rats. CSE (250 mg/kg, p.o.) alone did not affect the generation of LTP by application of subthreshold or suprathreshold tetanic stimulation (20 or 30 pulses at 60 Hz). Oral administration of ethanol (10–30%, 10 mL/kg) blocked the LTP induced by tetanic stimulation of 30 pulses at 60 Hz, but the LTP-blocking effect of ethanol was significantly attenuated by pre-administration of CSE (125 and 250 mg/kg, p.o.). The blockade of LTP induction by intravenously injected ethanol (30%, 2 mL/kg) was also antagonized by administration of CSE at doses of 125 and 250 mg/kg (p.o.). Oral administration of CSE antagonized also the LTP-blocking effect of ethanol directly injected into the brain, although it required a higher dose (500 mg/kg, p.o.). These results suggest that oral administration of CSE exerts an antagonistic effect on ethanol-induced impairment of hippocampal synaptic plasticity, which is possibly mediated by both direct action on the central nervous system and peripheral action.     

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.     

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.     

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.     

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.     

Effect of Salvia officinalis L. leaves on serum glucose and insulin in healthy and streptozotocin-induced diabetic rats

The leaves of sage (Salvia officinalis L., Lamiaceae) are reported to have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. To determine the hypoglycaemic effect of sage leaves, we investigated the effects of essential oil and methanolic effect of the plant on healthy and streptozotocin-induced diabetic rats. The animals were made diabetic using by streptozotocin (70 mg/kg, i.p.). The methanolic extract (100, 250, 400 and 500 mg/kg) and essential oil (0.042, 0.125, 0.2 and 0.4 ml/kg) were injected intraperitoneally. The control groups were administered water and sunflower oil as vehicles of methanolic extract and essential oil, respectively. Blood samples were obtained from retro-orbital sinus before administration and 1, 3 and 5 h after administrations. The serum glucose was measured by the enzymatic method of glucose oxidase. The results showed that the essential oil of sage did not change serum glucose, while the plant extract significantly decreased serum glucose in diabetic rats in 3 h without effect on insulin releasing from the pancreas but not in healthy rats. Also, the LD₅₀ of the methanolic extract is measured (4000 mg/kg, i.p.). The present data indicate that sage extract has hypoglycaemic effect on diabetic animals and the plant should be considered in future therapeutic researches.     

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.     

Effects of Hypericum montbretti Extract on the Central Nervous System and Involvement of GABA (A)/Benzodiazepine Receptors in its Pharmacological Activity

The present study was undertaken to investigate the putative activity of a methanol extract of Hypericum montbretti (Guttiferae) on the central nervous system. Rutin (1519 ppm) and quercitrin (784 ppm) were identified as the major phenolic compounds in the extract. When administered at 25, 50 and 100 mg/kg doses, the extract decreased the total number of head‐dipping behaviours performed by mice during a hole‐board test. Administration of both the extract and diazepam (2 mg/kg) reduced spontaneous locomotory activity, potentiated hexobarbital (60 mg/kg)‐induced sleeping parameters and prevented pentylenetetrazole (80 mg/kg)‐induced seizures relative to the controls. These findings are the first to indicate the sedative and anticonvulsant activities of H. montbretti extract. Atropine (2 mg/kg) and naloxone (5 mg/kg) pre‐treatment did not reverse the sedative effect, indicating that muscarinic and opioidergic mechanisms did not contribute to the pharmacological action. However, pre‐treatment with flumazenil (a benzodiazepine receptor antagonist) reversed both the sedative and anticonvulsant effects induced by a 100 mg/kg dose of the extract, indicating the involvement of the GABA(A)‐benzodiazepine receptor complex. In conclusion, H. montbretti extract is a novel candidate as a sedative and anticonvulsant drug for the treatment of sleep disorders and for the prevention of epileptic seizures. Copyright © 2012 John Wiley & Sons, Ltd.     

Anxiolytic and sedative activities of Passiflora edulis f. flavicarpa

Aim of the study

Many plants in the genus Passiflora have long been used in traditional folk medicines as a remedy for many neurogenic diseases in many countries. A number of species of the genus was studied about their neuropharmacological activities, but the results were inconsistent. No literature reported neuropharmacological studies on Passiflora edulis f. flavicarpa as yet. The present study was aimed at evaluating the anxiolytic and sedative activities of Passiflora edulis f. flavicarpa.

Materials and methods

Swiss albino mice were used as experimental animals in elevated plus-maze (EPM) test and spontaneous activity (SA) test to assay the behavioral effects of ethanolic extract (EE) of the aerial part of Passiflora edulis f. flavicarpa and its fractions, viz. petrol ether extract (PEE), ethyl acetate extract (EAE), n-BuOH extract (BE) and aqueous extract (AE), together with subfractions of BE, viz. BEF-I, BEF-II, BEF-III, BEF-IV and isoorientin, a flavonoid component isolated from BEF-III.

Results

In the EPM test, single-dose oral administration of EE (300 mg/kg and 400 mg/kg), BE (125 mg/kg and 200 mg/kg), AE (200 mg/kg and 300 mg/kg), BEF-I (200 mg/kg), BEF-II (200 mg/kg), BEF-III (100 mg/kg), or isoorientin (20 mg/kg) resulted in anxiolytic-like effects, but a sedative-like activity was produced at higher doses, such as 300 mg/kg of BE, 200 mg/kg of BEF-III, or 40 mg/kg and 80 mg/kg of isoorientin. The results of the SA test manifested that treatment with 400 mg/kg of EE, 300 mg/kg of BE, or 40 mg/kg and 80 mg/kg of isoorientin compromised motor activity in mice, which are in line with the results of the EPM test.

Conclusions

The aerial part of Passiflora edulis f. flavicarpa was anxiolytic at low dose but sedative at high dose. Flavonoids are important active constituents. Since AE contained little flavonoids, it was conjectured that there were other components responsible for the anxiolytic effect of Passiflora edulis f. flavicarpa besides flavonoids.     

Anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) leaf extract in mice

The anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) was investigated by studying the effects of both aqueous and methanol extracts of the plant species on seizures induced by pentylenetetrazole, bicuculline, picrotoxin and N-methyl-dl-aspartic in mice. Aqueous extract of Cotyledon orbiculata (50-400mg/kg, i.p.) and methanol extract (100-400mg/kg, i.p.) significantly prolonged the onset of tonic seizures induced by pentylenetetrazole (95mg/kg, i.p.). Methanol extract (400mg/kg, i.p.) also significantly reduced the incidence of the seizures. One hundred to two hundred milligrams/kilogram (i.p.) of aqueous extract of Cotyledon orbiculata significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.), picrotoxin (12mg/kg, i.p.) and N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.). Similarly, methanol extract (100-400mg/kg, i.p.) significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.) while 100mg/kg (i.p.) significantly delayed the onset of N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.)-induced seizures. Methanol extract (200mg/kg, i.p.) significantly reduced the incidence of the seizures induced by bicuculline (40mg/kg, i.p.). Phenobarbitone (12mg/kg, i.p.) and diazepam (0.5mg/kg, i.p.) effectively antagonized only seizures induced by PTZ (95mg/kg, i.p.), bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.). Phenytoin (30mg/kg, i.p.) did not affect any of the seizures to any significant extent. The data obtained suggest that both aqueous and methanol extracts of Cotyledon orbiculata have anticonvulsant property and may probably be affecting both gabaergic and glutaminergic mechanisms to exert its effect. The phytochemical analysis carried out revealed the presence of cardiac glycosides, saponins, tannins, reducing sugar and triterpene steroids in the plant extract.     

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.