CNS depressant and anticonvulsant activities of the alcoholic extract of leaves of Ziziyphus nummularia

Ethnopharmacological relevance

Ziziyphus nummularia (family: Rhamnaceae) is a xerophyte, grows in the grazing lands of the Thar Desert of Rajasthan. Ziziyphus nummularia (ZN) is used as sedative in ethnomedicine. The objective of this study is to investigate the anticonvulsant, anxiolytic and sedative activities of the alcoholic extract of leaves of Ziziyphus nummularia (EZN).

Materials and methods

The anticonvulsant effect of the EZN (100, 200 and 300 mg/kg) was evaluated in mice using the pentylenetetrazole and maximal electroshock induced seizure models. Its anxiolytic activity was evaluated using the elevated plus maze, hole board and open field models board methods, while the pentobarbital induced sleep was used to evaluate the sedative activity. The acute toxicity and effect on motor coordination were also assessed.

Results

EZN (100–300 mg/kg) protected the mice against the pentylenetetrazole induced convulsions; it causes a significant (P<0.05) dose dependent increase in latency of convulsion. Treatment with EZN reduced the duration of the tonic hind limb extension induced by electroshock. Mice treated with EZN preferred the open arm of the plus maze and were found to be devoid of open-arm avoidance. EZN potentiation the barbiturate induce sleep in mice, it causes a decrease in the sleep latency and increases the duration of sleep.

Conclusion

The results obtained from the experiments indicate that the EZN has CNS depressant and anticonvulsant activities.     

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.     

Anxiolytic-like effect of Sonchus oleraceus L. in mice

Ethnopharmacological relevance

Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system.

Aim of the study

This study was conducted to establish the anxiolytic effect of extracts from the aerial parts of Sonchus oleraceus.

Materials and methods

This study evaluated the effect of hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice submitted to the elevated plus-maze and open-field tests. Clonazepam was used as the standard drug.

Results

In the elevated plus-maze test, the Sonchus oleraceus extracts increased the percentage of open arm entries (P < 0.05) and time spent in the open-arm portions of the maze (P < 0.05). The extracts induce an anti-thigmotactic effect, evidenced by increased locomotor activity into the central part of the open field set-up (P < 0.05). The extracts administered at 30–300 mg/kg, p.o. had a similar anxiolytic effect to clonazepam (0.5 mg/kg, p.o.).

Conclusion

These data indicate that Sonchus oleraceus extract exerts an anxiolytic-like effect on mice.     

Anticonvulsant,anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata Fresen.

Aim of the study

The objective of this study is to investigate the anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata.

Materials and methods

The anticonvulsant effect of the aqueous root extract (100, 200 and 400 mg/kg) was evaluated in mice using the strychnine- and picrotoxin-induced seizure models. Its anxiolytic activity was evaluated using the elevated plus maze (EPM) and the Y maze (YM) methods (14 and 32) while the hexobarbitone induced sleep and the hole board models were used to evaluate the sedative and exploratory activities in mice respectively. The acute toxicity studies and phytochemical analysis of the extract were also carried out.

Results

The extract (100–400 mg/kg) produced a significant (P < 0.01) dose dependent increase in onset of convulsion compared to the control for strychnine- and picrotoxin-induced seizures. It also produced a significant (P < 0.01) dose dependent prolongation of the cumulative time spent in the open arms of the elevated plus maze and Y maze compared with the control. The extract (100–400 mg/kg) produced significant (P < 0.01) reduction in the time of onset of sleep induced by hexobarbitone. The prolongation of hexobarbitone sleeping time by the extract (200 mg/kg) was comparable to that produced by diazepam (3 mg/kg). At doses of 100–400 mg/kg, the extract produced a dose dependent decrease in exploratory activity of the mice. The reduction in exploratory activity produced by the extract (400 mg/kg) was greater than that of chlorpromazine (1 mg/kg). The results obtained from the experiments indicate that the extract has central nervous system depressant and anxiolytic activities. The LD₅₀ obtained for the acute toxicity studies using both oral and intraperitoneal routes of administration were 1.74 g/kg and 19.95 mg/kg respectively.

Conclusion

These findings justify the use of Securidaca longepedunculata in traditional medicine for the management of convulsion and psychosis.     

Pro-cognitive effects of Cirsium rivulare extracts in rats

Aim of the study

Cirsium rivulare (Jacq.) All. (Asteraceae) is a herbaceous perennial plant occurring in Central Europe. It has been traditionally used in Polish folk medicine to treat anxiety. In the present study methanolic extracts from flowers and leaves of Cirsium rivulare containing flavonoid compounds linarin, pectolinarin, apigenin, hispidulin, their glycosides and a newly isolated compound isokaemferide 7-O-(6″-methylglucuronide) were studied for anxiolytic and pro-cognitive properties.

Materials and methods

Male Wistar rats (150–160 g) were used. They were treated orally with standardized methanol extracts of flowers and leaves of Cirsium rivulare and subsequently tested for memory in passive avoidance (PA) and object recognition (OR) tests. Auxiliary tests for motor (open field, OF) and emotional (elevated ‘plus’ maze, EPM) effects of the above treatments were also employed.

Results

We found that the extract from flowers of Cirsium rivulare, in addition to its anxiolytic effects as measured in the EPM, improves memory of the appetitively (by curiosity, OR) and aversively (by footshook, PA) motivated tasks. This is in contrast to classical anxiolytics as for example benzodiazepines that typically impair memory. The extract from leaves of Cirsium rivulare showed some anxiolytic properties in the EPM, and no effect in both cognitive tests. The examined extracts of Cirsium rivulare did not affect psychomotor exploratory activity of rats tested in the OF.

Conclusions

These results suggest that the flavonoids from Cirsium rivulare possess anxiolytic and pro-cognitive effects, the extract from flowers being more pro-cognitive and that from the leaves more anxiolytic.     

Isolation of jacaranone,a sedative constituent extracted from the flowers of the Mexican tree Ternstroemia pringlei

Ethnopharmacological relevance

Ternstroemia pringlei represents one of the most widely employed and commercially exploited medicinal plant in Mexico, used popularly as a tranquilizer and for the treatment of insomnia.

Aim of the study

To investigate the sedative constituents of the plant through a bio-guided fractionation of extracts derived from calyx and fruits.

Materials and methods

Crude extracts with different polarities (CHCl₃, AcOEt, MeOH, aqueous) were prepared and subjected to chromatographic fractionation, leading to the isolation of the sedative compound (1) from the MeOH crude extract. The identity of 1 was unequivocally established by means of 1D and 2D NMR spectroscopic analysis. The sleeping time induced by sodium pentobarbital and the elevated plus-maze models were performed on mice to determine the sedative and anxiolytic activities, respectively. Bioactivity was also investigated though in vitro GABA release experiments using mice brain slices.

Results

The sedative compound was established as jacaranone (1), and its effect was clearly demonstrated through a dose-dependent response analysis (ED₅₀ = 25 mg/kg mouse weight). When tested in the elevated plus-maze model, none of the extracts from Ternstroemia pringlei displayed anxiolytic activity. GABA release experiments showed that the MeOH and aqueous crude extracts released this neurotransmitter at a ratio of 217 and 179 pmol/g protein, respectively, evidencing the presence of other bioactive constituents in the extracts apart of 1, whose activity was absent in this model.

Conclusions

Although 1 has been isolated and identified in a number of plant species, this is the first time that its sedative effect has been demonstrated. No previous record exists of other sedative compounds having been isolated from Ternstroemia pringlei.     

Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects

Aim of the study

Various parts of Carica papaya Linn. (CP) have been traditionally used as ethnomedicine for a number of disorders, including cancer. There have been anecdotes of patients with advanced cancers achieving remission following consumption of tea extract made from CP leaves. However, the precise cellular mechanism of action of CP tea extracts remains unclear. The aim of the present study is to examine the effect of aqueous-extracted CP leaf fraction on the growth of various tumor cell lines and on the anti-tumor effect of human lymphocytes. In addition, we attempted to identify the functional molecular weight fraction in the CP leaf extract.

Materials and methods

The effect of CP extract on the proliferative responses of tumor cell lines and human peripheral blood mononuclear cells (PBMC), and cytotoxic activities of PBMC were assessed by [³H]-thymidine incorporation. Flow cytometric analysis and measurement of caspase-3/7 activities were performed to confirm the induction of apoptosis on tumor cells. Cytokine productions by PBMC were measured by ELISA. Gene profiling of the effect of CP extract treatment was performed by microarray analysis and real-time RT-PCR.

Results

We observed significant growth inhibitory activity of the CP extract on tumor cell lines. In PBMC, the production of IL-2 and IL-4 was reduced following the addition of CP extract, whereas that of IL-12p40, IL-12p70, IFN-γ and TNF-α was enhanced without growth inhibition. In addition, cytotoxicity of activated PBMC against K562 was enhanced by the addition of CP extract. Moreover, microarray analyses showed that the expression of 23 immunomodulatory genes, classified by gene ontology analysis, was enhanced by the addition of CP extract. In this regard, CCL2, CCL7, CCL8 and SERPINB2 were representative of these upregulated genes, and thus may serve as index markers of the immunomodulatory effects of CP extract. Finally, we identified the active components of CP extract, which inhibits tumor cell growth and stimulates anti-tumor effects, to be the fraction with M.W. less than 1000.

Conclusion

Since Carica papaya leaf extract can mediate a Th1 type shift in human immune system, our results suggest that the CP leaf extract may potentially provide the means for the treatment and prevention of selected human diseases such as cancer, various allergic disorders, and may also serve as immunoadjuvant for vaccine therapy.     

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.     

Repeated administration of an aqueous spray-dried extract of the leaves of Passiflora alata Curtis (Passifloraceae) inhibits body weight gain without altering mice behavior

Ethnopharmacological relevance

Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce.

Aim of the study

To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice.

Material and methods

Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250 mg/kg). The feeding behavior was evaluated at the beginning (1 h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed.

Results

The repeated treatment with the highest dose tested (250 mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level.

Conclusions

These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic.     

Wound healing properties of Carica papaya latex: In vivo evaluation in mice burn model

Ethnopharmacological relevance

Carica papaya is traditionally used to treat various skin disorders, including wounds. It is widely used in developing countries as an effective and readily available treatment of various wounds, particularly burns.

The aim of the study

This study was aimed at investigating the healing efficiency of papaya latex formulated as 1.0 and 2.5% hydrogels.

Materials and methods

Burns were induced in Swiss albino mice divided into five groups as following; Group-I (negative control) received no treatment. Group-II was treated with Carbopol 974P NF empty gel. Groups-III and -IV were treated with Carbopol gel containing 1.0 and 2.5% of dried papaya latex, respectively. Group-V (positive control) received the standard drug (silver sulphadiazine and chlorhexidine gluconate cream). The efficacy of treatment was evaluated based on the hydroxyproline content, wound contraction and epithelialization time.

Results

Hydroxyproline content was found to be significantly increased in the Group-III. Significant increase in percentage wound contraction was observed from day 12 in Group-IV and from day 20 in Groups-III and -V. The epithelialization time was found to be the shortest in Group-IV.

Conclusion

It may be concluded that papaya latex formulated in the Carbopol gel is effective in the treatment of burns and thus supports its traditional use.     

Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice

Ethnopharmacological relevance

Moringa oleifera (family Moringaceae), commonly called Horseradish or tree of life, is traditionally used for the treatment of epilepsy and neurologic conditions.

Aim of the study

The objective of this study is to investigate the neurobehavioural and anticonvulsant properties of the ethanol extract from the leaves of Moringa oleifera.

Materials and methods

Neurobehavioural properties were evaluated using the open field, hole board, Y-maze, elevated plus maze (EPM) and pentobarbitone-induced hypnosis. Pentylenetetrazole (leptazol), picrotoxin and strychnine induced convulsion tests were used to investigate the anti-convulsive actions of Moringa oleifera.

Results

The result showed that the extract (250–2000 mg/kg) caused a significant dose-dependent decrease in rearing, grooming, head dips and locomotion (P<0.001). It also enhanced learning and memory and increased anxiogenic effect. In addition, the extract (2000 mg/kg) protected mice against pentylenetetrazol induced convulsion, but has no effect on picrotoxin and strychnine induced convulsion. The effects of the extract in the various models were comparable to those of the standard drugs used except in Y-maze, EPM and picrotoxin and strychnine induced convulsion. The LD₅₀ obtained for the acute toxicity studied using oral route of administration was >6.4 g/kg.

Conclusion

The findings from this study suggest that the ethanol extract of Moringa oleifera leaves possesses CNS depressant and anticonvulsant activities possibly mediated through the enhancement of central inhibitory mechanism involving release γ-amino butyric acid (GABA). The results partially justified the traditional use of the extract for the treatment of epilepsy.     

Central depressant activity of butanol fraction of Securinega virosa root bark in mice

Ethnopharmacological relevance

Securinega virosa is a commonly used medicinal plant in African traditional medicine in the management of epilepsy and mental illness. Previous studies in our laboratory showed that the crude methanol root bark extract of the plant possesses significant behavioral effect in laboratory animals. In an attempt to isolate and characterize the biological principles responsible for the observed activity, this study is aimed at evaluating the central depressant activity of the butanol fraction of the methanol root bark extract of Securinega virosa.

Materials and methods

The medial lethal dose of the butanol fraction was estimated using the method of Lorke. Preliminary phytochemical screening was conducted on the butanol fraction using standard protocol. The behavioral effect of the butanol fraction (75, 150 and 300 mg/kg) was evaluated using diazepam induced sleep test, hole-board test, beam walking assay, staircase test, open field test and elevated plus maze assay, all in mice.

Results

The median lethal dose of the butanol fraction was estimated to be 1256.9 mg/kg. The preliminary phytochemical screening revealed the presence of tannins, saponins, alkaloids, flavonoids, cardiac glycosides, similar to those found in the crude methanol extract. The butanol fraction significantly (P < 0.001) reduced the mean onset of sleep in mice and doubled the mean duration of sleep in mice at the dose of 75 mg/kg. The butanol fraction and diazepam (0.5 mg/kg) significantly (P < 0.01–0.001) reduced the number of head dips in the hole-board test suggesting sedative effect. The sedative effect of the butanol fraction was further corroborated by its significant (P < 0.01–0.001) reduction of the number of step climbed and rearing in the staircase test. The butanol fraction did not significantly increase the time taken to complete the task and number of foot slips in the beam walking assay, suggesting that it does not induce significant motor coordination deficit. Diazepam (2 mg/kg), the standard agent used significantly (P < 0.01) increased the number of foot slips. In the open field test, the butanol fraction significantly reduced the number of square crossed as well as the number of rearing. However, the butanol fraction did not significantly alter the behavior of mice in the elevated plus maze assay, while diazepam (0.5 mg/kg) significantly (P < 0.05) increased the time spent in the open arm and reduced the number of closed arm entry.

Conclusion

The findings of this study suggest that the butanol fraction of Securinega virosa root bark contains some bioactive principles that are sedative in nature.     

Anxiolytic effects of standardized extract of Centella asiatica (ECa 233) after chronic immobilization stress in mice

Ethnopharmacological relevance

Centella asiatica has long been used for various neurological disturbances in Southeast Asian countries. The present study aims to demonstrate the anxiolytic effect of ECa 233, a standardized extract of C. asiatica containing triterpenoids not less than 80%, in comparison to diazepam.

Materials and methods

The test compound was given orally to non-stressed mice and mice subjected to chronic immobilization stress. Anxiolytic effect was assessed by an elevated plus maze (EPM), a dark-light box and an open-field tests.

Results

Anxiolytic effect of ECa 233 was clearly demonstrated in non-stressed mice subjected to acute stress in all behavioral tests employed. In the EPM test, chronically stressed mice showed significant decrease in the number of open arm entries, shortening the time spent in open arms and an increase of the latency to leave the central area, suggesting their release from the stress. In addition, ameliorating effect of ECa 233 was observed on the body weight and serum corticosterone which were adversely affected by immobilization stress. Madecassoside and asiaticoside, equal to their respective contents of the effective doses of ECa 233, exclusively presented anxiolytic effects in EPM, while no distinct effect was observed on the body weight and serum corticosterone.

Conclusions

The present study demonstrated anxiolytic effect of ECa 233 in both acutely and chronically stressed animals. These effects could be mainly accounted by madecassoside and asiaticoside, suggesting a possible use of ECa 233 for the treatment of both acute and chronic anxiety in the pathological state.     

Antinociceptive,neurobehavioral and antioxidant effects of Eupatorium triplinerve Vahl on rats

Ethnopharmacological relevance

Eupatorium triplinerve Vahl belongs to the Asteraceae family, popularly known as Japana. It is a perennial shrub native to Amazon rainforests of South America. Its leaves are used through infusions, decoctions, baths, and tea. It is largely used in Brazilian folk medicine as sedative, febrifuge, stimulant, tonic and anti-inflammatory.

Aim of the study

The present study evaluated the putative effects of Eupatorium triplinerve on the central nervous system (CNS), including locomotor and anxiety activity, depression-like behavior, and antinociception and oxidative stress.

Materials and methods

Two-month-old male Wistar rats (n=7–10 rats/group) and Swiss male and female mice of the species Mus musculus (n=7–10 per group) were administered with 100 mg/kg, 200 mg/kg, 400 mg/kg, 600 mg/kg, and 800 mg/kg of hydroalcoholic extracts of Eupatorium triplinerve (HEET). The behavioral assays included open-field (OF), elevated Plus-maze (EPM), and forced swimming tests (FS). The antinociceptive activity was verified using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception. The oxidative stress levels were measured in rat blood samples after behavioral assays and Trolox equivalent antioxidant capacity (TEAC), nitric oxide and malondialdehyde (MDA) levels were measured in vivo.

Results

Oral pretreatment with HEET reduced the locomotion in OF test (200–800 mg/kg), increased central locomotion and open arms entries in the OF and EPM tests, respectively (600–800 mg/kg), and decreased the immobility time in the FS (200–800 mg/kg). It also reduced the writhing number evoked by acetic acid injection (200–800 mg/kg) and licking time in the first phase of the formalin test (400–800 mg/kg). In the oxidative stress assays, the extract decreased TEAC, Nitric Oxide and MDA levels in response to swimming stress induced in rats.

Conclusions

These results were indicative for the first time that Eupatorium triplinerve exerted mild sedative, anxiolytic and antidepressive effects on the CNS. Antinociceptive effects not related to opioid system and antioxidant activity were also observed. These results support the ethnopharmacological use of Eupatorium triplinerve in popular medicine.     

Depressant effects of Clinopodium mexicanum Benth. Govaerts (Lamiaceae) on the central nervous system

Ethnopharmacological relevance

The decoction of leaves of Clinopodium mexicanum Benth. Goaverts (Lamiaceae), commonly known as “Toronjil de Monte”, is used in the Mexican traditional medicine to induce sleep, as well as sedative and analgesic remedy.

Aim of the study

To evaluate the putative depressant effects of an aqueous extract of the medicinal plant Clinopodium mexicanum on the central nervous system (CNS).

Materials and methods

The effects of the extract (AECM) on mice were tested in several animal paradigms, including sodium pentobarbital-induced sleep, open field tests, and hole-board tests. The effects of AECM on pentylenetetrazole- and picrotoxin-induced convulsions in mice and on the antithermonociceptive response in the hot-plate paradigm were also tested. Additionally, the active extract (AECM) was analyzed with HPLC–ESI-MS techniques.

Results

Mice acutely treated with AECM at 100, 200, 500 and 1000 mg/kg doses prolonged the sleeping time induced by sodium pentobarbital (42 mg/kg). This extract, at 100 and 200 mg/kg doses, showed a sedative effect in the hole-board paradigm and decreased spontaneous activity in mice. AECM at 10, 100 and 200 mg/kg prolonged the onset of seizures induced by pentylenetetrazole (90 mg/kg) and antagonized tonic convulsions induced by picrotoxin (10 mg/kg). Additionally, AECM inhibited the response to a thermonociceptive stimulus. The intraperitoneal AECM treatment produced mortality with an LD₅₀ = 2154 mg/kg. Chemical analysis showed that the flavanone glycosides neoponcirin, poncirin, and isonaringenin are the main compounds of the active extract.

Conclusions

This study demonstrates that an acutely administered single dose of an aqueous extract of Clinopodium mexicanum can exert depressant effects on the CNS. These findings are in agreement with the traditional use of Clinopodium mexicanum to induce sleep as well as sedative and analgesic remedy. The chemical analysis of AECM revealed the presence of the flavanone glycosides neoponcirin, poncirin, and isonaringin.     

Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer's disease model

Ethnopharmacological relevance

Bacopa monnieri (L.) Wettst., a plant belonging to the family Scrophulariaceae, has been used in the traditional system of Ayurvedic medicine to improve intelligence and memory for a long time. Therefore, the potential of this plant to protect against Alzheimer's disease has been raised but less supported document is available.

Aim of the study

To determine the effect of alcoholic extract of Bacopa monnieri on cognitive function and neurodegeneration in animal model of Alzheimer's disease induced by ethylcholine aziridinium ion (AF64A).

Materials and methods

Male Wistar rats were orally given the alcoholic extract of Bacopa monnieri at doses of 20, 40 and 80 mg/kg BW via feeding needle for a period of 2 weeks before and 1 week after the intracerebroventricular administration of AF64A bilaterally. Rats were tested for spatial memory using Morris water maze test and the density of neurons and cholinergic neurons was determined using histological techniques 7 days after AF64A administration.

Results

Bacopa monnieri extract improved the escape latency time (p < .01) in Morris water maze test. Moreover, the reduction of neurons and cholinergic neuron densities were also mitigated.

Conclusion

These findings suggest that Bacopa monnieri is a potential cognitive enhancer and neuroprotectant against Alzheimer's disease.     

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.     

Behavioral properties of Balanites aegyptiaca in rodents

Ethnopharmacological relevance

Balanites aegyptiaca is a native plant from the dry tropical areas of Africa and Arabia. It has been used in traditional medicine to treat psychoses, epilepsy, rheumatism and for the management of cough, liver and spleen conditions for many years. The plant is also used as antihelmintic and molluscicide.

Aim of the study

The present studies aimed at investigating the behavioral properties of ethanol extract of the root of this medicinal plant, which is already in common applications in the Nigerian traditional medicine.

Materials and methods

The intraperitoneal and oral mean lethal dose (LD₅₀) of the extract was determined using the Lorke's method. The preliminary phytochemical screening of the extract was carried out to identify the secondary metabolites in the extract. Furthermore, the behavioral properties of the extract were evaluated using diazepam-induced sleep, open field test, staircase test and beam walking assay all in mice.

Results

The extract significantly (p < 0.001) prolonged the duration diazepam (20 mg/kg i.p)-induced sleep in mice dose dependently. However, the extract showed no significant effect on the onset of diazepam-induced sleep. In the open field test, the extract (150 and 300 mg/kg) and diazepam (0.05 mg/kg) produced a significant (p < 0.05, p < 0.005 and p < 0.001) decrease in the number of square crossings. There was no significant effect on the number of centre square crossing following the administration of the extract. The extract (75 and 150 mg/kg) and diazepam (0.05 mg/kg) produced a significant (p < 0.05) decrease in the number of rearing suggestive of sedation. In the staircase experiment there was a decrease in the number of upward step climbing as well as number of rearing suggesting anxiolytic and sedative properties of the extract. In the beam walking assay the extract did not produce any significant increase in the time taken to complete task as compared to diazepam 1 mg/kg which was significant at p < 0.05. Furthermore, 300 mg/kg of the extract and diazepam 1 mg/kg showed significant (p < 0.05) mean number of foot slips, suggesting that the central nervous system depressant activity might not necessarily due to peripheral neuromuscular blockade.

Conclusion

The result indicates that the extract of Balanites aegyptiaca possess biologically active compound(s) that have anxiolytic and sedative properties, which support the ethnomedicinal use of the plant as antipsychotic and antiepileptic agents.