Anticonvulsant effect of Ficus religiosa: Role of serotonergic pathways

Ethnopharmacological relevance

Ficus religiosa (Moraceae) is reported to have numerous therapeutic utility in folk medicine. Among different biological activities on central nervous system, it has been reported to be used in ethnomedical treatment of epilepsy, which led us to further explore its anticonvulsant activity in various animal models of epilepsy.

Aim of the study

To investigate anticonvulsant activity of methanolic extract of figs of Ficus religiosa in animal models and to determine its possible anticonvulsant mechanism.

Materials and methods

Anticonvulsant activity of figs extract (25, 50 and 100 mg/kg, i.p.) was studied in seizures induced by maximum electroshock (MES), picrotoxin and pentylenetetrazol (PTZ). Cyproheptadine, a nonselective (5HT_1/2) serotonin antagonist (4 mg/kg, i.p.) was used to study the reversal of protective effect of extract in the above mentioned models. Acute toxicity, neurotoxicity and potentiation of pentobarbitone induced sleep by extract was also studied.

Results

Extract showed no toxicity, potentiated pentobarbitone induced sleep and inhibited seizures induced by MES and picrotoxin in a dose dependent manner. Anticonvulsant effect of extract was comparable to clinically used antiepileptic drugs (phenytoin and diazepam). However, PTZ induced seizures were not inhibited. Animals pretreated with cyproheptadine showed inhibition of the anticonvulsant effect of extract.

Conclusions

These findings suggested that the methanolic extract of figs of Ficus religiosa had anticonvulsant activity against MES and picrotoxin induced convulsions, with no neurotoxic effect, in a dose dependent manner. Inhibition of the anticonvulsant effect of extract by cyproheptadine substantiates the involvement of serotonergic pathways for the anticonvulsant activity of extract.     

Anticonvulsant activity of the essential oil and methanolic extract of Bunium persicum (Boiss). B. Fedtsch

Ethnopharmacological relevance

Bunium persicum is an endemic plant to Iran which its seeds have a long history of medicinal uses.

Aim of the study

This work aimed to study the anticonvulsant effect of the essential oil and methanolic extract of the plant.

Materials and methods

The essential oil and methanolic extract of the plant were studied against pentylenetetrazole (PTZ) and maximal electroshock (MES) induced convulsions in mice in different doses. The neurotoxicity of the essential oil and methanolic extract was investigated using rotarod method.

Results

The essential oil and methanolic extract prolonged the onset of clonic and tonic seizures in PTZ. The tonic seizures were prevented by essential oil in both methods at dose of 1 mL/kg and higher doses. The methanolic extract inhibited PTZ-convulsions at dose 3 g/kg and was ineffective against MES induced convulsion.

Conclusions

The essential oil of the plant might be useful to control absence and grand mal seizures at dose 1 mL/kg. This activity might be due to its content of monoterpenes.     

Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced seizure: a behavioral and EEG study in rats

Ethnopharmacological relevance

Marsilea quadrifolia Linn (MQ) extract has been used traditionally as sedative and antiepileptic drug in India.

Aim of this study

To investigate the anticonvulsive potential of MQ extracts by using behavior and electroencephalographic (EEG) analysis on pentylenetetrazole (PTZ) induced seizure model in rats.

Materials and methods

For anticonvulsant effect, 60 minutes after administration of MQ, behavior and EEG were analyzed during PTZ (60 mg/kg) induced seizures. Changes of EEG power, latency of onset of seizure, seizure severity score, and duration of epileptic seizure were determined.

Results

Both the water and ethanol extract of MQ increased the latency of seizure but also decreased duration of epileptic seizure and seizure severity score. This reduction of seizure severity was also observed in EEG recording and EEG power analysis. The effectiveness of MQ ethanol extract is better than MQ water extract.

Conclusion

Both water and ethanol extract of MQ were effective in reducing the severity of behavioral and EEG seizures induced by PTZ in rats. This study justifies the traditional use of this plant in epilepsy.     

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.     

Behavioral and anticonvulsant effects of the standardized extract of Ficus platyphylla stem bark

Ethnopharmacological relevance

Decoctions of Ficus platyphylla Del.-Holl (Family: Moraceae) are used in Nigeria?s folk medicine for the management of epilepsy and their efficacies are widely acclaimed among the rural communities of northern Nigeria. The aim of the study is to examine the behavioral and anticonvulsant properties of the standardized methanol extract of Ficus platyphylla (FP) stem bark, in order to scientifically describe its potential values in the management of convulsive disorders.

Materials and methods

High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the methanol extract were utilized and the intraperitoneal median lethal dose (LD₅₀) determined in mice. The effects of FP were investigated on some murine models of behavior and its anticonvulsant effects studied on pentylenetetrazole (PTZ)-, strychnine (STN)-, picrotoxin (PCT)-, isoniazid (INH)-, aminophylline (AMI)- and maximal electroshock (MES)-induced seizures in mice.

Results

The intraperitoneal oral LD₅₀ of FP was estimated to be 5000 mg/kg. FP significantly reduced the locomotor activities including the total distance covered, speed, active time and rearing counts. It shortened the onset and prolonged the duration of diazepam-induced sleep, but had no effect on motor coordination on the rota-rod treadmill or beam-walking assay in mice at the doses tested. The extract protected the mice against PTZ- and STN-induced seizures and significantly delayed the latencies of myoclonic jerks and tonic seizures induced by all the standard convulsant agents (PTZ, PCT, INH, STN and AMI) used in this study, but failed to protect the mice against MES seizures at the doses tested. The HPLC fingerprint of the extract shows a spectrum profile characteristic of Ficus platyphylla, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids and tannins.

Conclusion

Our study provides scientific evidence that FP may contain psychoactive principles with potential anticonvulsant properties, thus supporting further development of the psychoactive components of this plant as anticonvulsant agents.     

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.     

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.     

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.     

Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice

Ethnopharmacological relevance

Carica papaya has been used in the Ethiopian traditional medicine to relieve stress and other disease conditions.

Aim of the study

The present study was undertaken to evaluate the anxiolytic and sedative effects of 80% ethanolic Carica papaya (Caricaceae) pulp extract in mice.

Materials and methods

Carica papaya pulp extract was screened for anxiolytic effect by using elevated plus maze, staircase and open field tests, and ketamine-induced sleeping time test for sedation at doses of 50, 100, 200, 400 mg/kg. Distilled water and Diazepam were employed as negative and positive control groups, respectively.

Results

Carica papaya pulp extract 100 mg/kg significantly increased the percentage of open arm time and entry, and reduced the percentage of entry and time spent in closed arm in elevated plus maze test; reduced the number of rearing in the staircase test; and increased the time spent and entries in the central squares while the total number of entries into the open field were not significantly affected, suggesting anxiolytic activity without altering locomotor and sedative effects. A synergistic reduction in the number of rearing and an inverted U-shaped dose response curves were obtained with important parameters of anxiety

Conclusions

The results of this study established a support for the traditional usage of Carica papaya as anxiolytic medicinal plant.     

Neuropharmacological screening of essential oil from oleo gum resin of Gardenia lucida Roxb

Ethnopharmacological relevance

The oleo gum resin of Gardenia lucida is commonly employed in traditional medicine to treat multiple ailments, including epilepsy and mania. The essential oil isolated from it was screened for CNS activities to check if it is responsible for the claims made regarding the traditional use of the oleo gum resin.

Materials and methods

The hypnotic and anticonvulsant activity was assessed by pentobarbitone induced hypnosis and convulsant models—Maximum electroshock (MES) and Pentylene tetrazole (PTZ) respectively. Effect on motor activity was evaluated using an actophotometer, rotarod and grip strength methods.

Results

The oil significantly potentiated the barbitone induced hypnosis and offered significant protection against the intensity and frequency of convulsions and mortality rate in both the convulsant models. A significant decrease in locomotion, motor impairment and loss of gripping reflex was also observed.

Conclusion

The essential oil of the oleo gum resin of Gardenia lucida is a CNS depressant and anticonvulsant with central muscle relaxant properties. This justifies the claims made regarding the use of the oleo gum resin of Gardenia lucida in CNS disorders.     

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice

Ethnopharmacological relevance

Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America.

Aim of the study

To investigate the neuropharmacological properties on experimental animals.

Materials and methods

The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200 mg/kg.

Results

All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant.

Conclusion

Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.     

Anticonvulsant and antioxidative activity of hydroalcoholic extract of tuber of Orchis mascula in pentylenetetrazole and maximal electroshock induced seizures in rats

Ethnopharmacological relevance

Orchis mascula tuber is used in many polyherbal formulations as a nerve tonic in India.

Aim of the study

In the present study, effect of hydroalcholic extract of O. mascula (HEOM) tuber was evaluated against seizures, seizure-induced oxidative stress and cognitive deficit in pentylenetetrazole and maximal electroshock-induced seizures in rats.

Materials and methods

HEOM was administered orally 30 min before induction of seizures by pentylenetetrazole (PTZ; 60 mg/kg, i.p) or maximal electroshock (MES; 70 mA). Elevated plus maze and passive avoidance tests were used to assess the learning and memory. Oxidative stress was studied by estimation of reduced glutathione and lipid peroxidation. Whole brain total cholinesterase activity was also evaluated.

Results

HEOM produced 33.3%, 50% and 66.7% protection in PTZ model and 16.7%, 16.7% and 33.3% at 250, 500 and 1000 mg/kg, respectively, in MES-induced seizures. Pre-treatment with HEOM significantly decreased the retention transfer latency in elevated plus maze test, and an increase in the retention latency in passive avoidance test was observed. Oxidative stress induced by seizures was also attenuated as indicated by significant increase in GSH and decrease in MDA levels in HEOM treated groups. PTZ and MES caused a significant decrease in AChE and BChE activities, which was prevented by HEOM.

Conclusions

HEOM thus showed protection against seizures, prevented the associated memory impairment probably by modulating cholinergic status and reducing oxidative stress.     

Anthelmintic activity of Ziziphus nummularia (bark) and Acacia nilotica (fruit) against Trichostrongylid nematodes of sheep

Ethnopharmacological relevance

Ziziphus nummularia (Rhamnaceae) and Acacia nilotica (Fabaceae) are being used as anthelmintics in ethnoveterinary medicinal system of Pakistan.

Aim of the study

Present study was conducted to determine the anthelmintic activity of Ziziphus nummularia (bark) and Acacia nilotica (fruit) in order to justify their traditional use in veterinary medicine.

Materials and methods

In vitro anthelmintic activity of crude methanolic extract (CME) of both the plants was determined against Haemonchus contortus by the adult motility assay, the egg hatch test and the larval development assay. In vivo anthelmintic activity was evaluated in sheep naturally infected with gastrointestinal nematodes by administering increasing doses of crude powder (CP) and CME (1.0–3.0 g/kg).

Results

Both the plants exhibited dose- and time-dependent anthelmintic effects by causing mortality of worms, and inhibiting egg hatching and larval development. Acacia nilotica (LC₅₀ = 512.86 and 194.98 μg/ml) was found to be more potent than Ziziphus nummularia (LC₅₀ = 676.08 and 398.11 μg/ml) in egg hatch test and larval development assay, respectively. In vivo, maximum fecal egg count reduction (84.7%) was recorded on day 13 post-treatment in sheep treated with Ziziphus nummularia CME (3.0 g/kg) followed by 78.5% on same day with Acacia nilotica CME (3.0 g/kg).

Conclusions

These data show that both Ziziphus nummularia and Acacia nilotica possess anthelmintic activity in vitro and in vivo, justifying their use in traditional veterinary medicine in Pakistan.     

Neuropharmacological study of Dracocephalum moldavica L. (Lamiaceae) in mice: sedative effect and chemical analysis of an aqueous extract

Ethnopharmacological relevance

Dracocephalum moldavica is used as a tranquilizer and as remedy for nervous conditions relief in the Mexican traditional medicine. Despite its intensive use no literature reported neuropharmacological studies on Dracocephalum moldavica as yet.

Aim of the study

The sedative, anxiolytic-like and antidepressant-like effects of the aqueous extract of aerial parts of Dracocephalum moldavica (Lamiaceae) (DM) were evaluated in behavioral models in mice. The general toxic effects of DM were evaluated as well as their chemical analysis was performed.

Materials and methods

DM effects were evaluated on pentobarbital-induced sleeping time (SPT), the hole-board (HBT), and the avoidance exploratory behavior (AEBT) tests and on the forced swimming test (FST). General activity and motor coordination were evaluated in the open field (OFT) and Rota-rod tests, respectively. The acute toxicity of DM was determinate by its LD₅₀ dose. The chemical analyses DM were performed by chromatographic and HPLC–ESI-MS techniques.

Results

DM prolonged the pentobarbital-induced sleeping time, induced sedation in the HBT, decreased spontaneous activity and produced motor coordination impairment in mice. However, DM did not show anxiolytic effects in the AEBT or HBT and it was not effective in FST. The DM-treatment produced mortalities with LD₅₀ = 470 mg/kg body weight.The HPLC–ESI-MS analysis of DM revealed that (acacetin, apigenin and luteolin)-7-O-β-d-(6″-O-malonyl)-glucoside derivates are the main compounds of DM.

Conclusions

DM induced sedative actions and a general inhibition of CNS activity observed by the decrease of animals’ general activity, motor coordination and exploration.     

Central nervous system effects and chemical composition of two subspecies of Agastache mexicana; an ethnomedicine of Mexico

Ethnopharmacological relevance

Agastache mexicana subspecies mexicana (Amm) and xolocotziana (Amx) are used in Mexican traditional medicine to relief cultural affiliation syndromes known as “susto” or “espanto”, for “nervous” condition, and as a sleep aid. Despite its intensive use, neuropharmacological studies are scarce, and the chemical composition of the aqueous extracts has not been described. Aims of the study are: (1) To analyze the chemical composition of aqueous extracts from aerial parts of Amm and Amx. (2) To evaluate the anxiolytic-like, sedative, antidepressant-like effects. (3) Analyze the general toxic effects of different doses.

Materials and methods

Anxiolytic-like and sedative effects were measured in the avoidance exploratory behavior, burying behavior and the hole-board tests. The antidepressant-like actions were studied in the forced swimming and tail suspension tests. Finally, general activity and motor coordination disturbances were evaluated in the open field, inverted screen and rota-rod tests. The acute toxicity of Amm and Amx was determined by calculating their LD₅₀ (mean lethal dose). The chemical analyses were performed employing chromatographic, photometric and HPLC–ESI-MS techniques.

Results

Low doses of Amm and Amx (0.1σ1.0 mg/kg) induced anxiolytic-like actions; while higher doses (over 10 mg/kg) induced sedation and reduced the locomotor activity, exerting a general inhibition in the central nervous system (CNS).

Conclusions

Results support the use of Amm and Amx in traditional medicine as tranquilizers and sleep inducers. Additionally, this paper contributes to the knowledge of the chemical composition of the aqueous extracts of these plants.     

Sedative activity of hexane extract of Keampferia galanga L. and its active compounds

Ethnopharmacological relevance

It is well known that fragrance impacts behaviors and autonomic functions, and is increasingly used as relaxant, carminative, as well as sedative in aromatherapy. Kaempferia galanga L. is one of the popular traditional aromatic medicinal plants used in tropics and subtropics of Asia including China, Japan and Indochina.

Aim of the study

The aim of present study was to investigate sedative effects of hexane extract of Kaempferia galanga L.and 2 active aromatic compounds (compound 1: ethyl trans-p-methoxycinnamate and compound 2: ethyl cinnamate ) included in the extyract by means of inhalation in mice.

Materials and methods

Sedative activity was assessed by inhalation of the hexane extract and two major aromatic compounds.

Results

Inhalation of hexane extract at the doses of 1.5 and 10 mg showed significant reduction of locomotor activity, indicating considerable sedative and relaxant effects. Compound 1 and 2 were proved to possess sedative effects at 0.0014 mg and 0.0012 mg respectively.

Conclusions

These results suggest the promising application of Kaempferia galanga L. and its constituents in aromatherapy.     

Evaluation of the effects of Astragalus mongholicus Bunge saponin extract on central nervous system functions

Ethnopharmacological relevance

In traditional medicine, Astragalus mongholicus (AM) has been used for the treatment of general weakness, chronic illness, and to increase overall vitality.

Aim of the study

The present study investigated possible effects of the saponin fraction of AM on the central nervous system. Moreover, its effects on locomotor activity, anxiety, and hippocampal morphology were studied.

Material and methods

AM extract was tested for its effects on locomotor activity using the Moti-Test, for situational anxiety in the elevated plus maze, and for anticonvulsant activity against acute pentylenetetrazole (PTZ)-induced seizures and in the PTZ kindling model.

Results

It was shown that AM (50, 100, 200 mg/kg) did not interfere with locomotor activity and situational anxiety as measured in the elevated plus maze. In these doses, AM significantly suppressed pentylenetetrazole (PTZ)-induced seizures (p < 0.05). Its anticonvulsant efficacy was also evident against repeated PTZ seizures (p < 0.05). This suggests potential therapeutic usefulness. After subchronic application, the number of cells in hippocampal CA1 was reduced, whilst the cell number in CA3 and hilus remained unaffected.

Conclusions

Doses of AM extract which did not interfere with locomotor acticity and situational anxiety appear to be useful in the treatment of convulsive disorders. The mechanisms underlying this effect on hippocampal morphology are not yet understood.     

Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum

Ethnopharmacological relevance

Rhizoma Pinelliae Praeparatum is the product of raw Rhizoma Pinellia processed with alkaline solution and Licorice, which had been widely used for treatment of insomnia in traditional Chinese medicine. The present study aimed to investigate the sedative, hypnotic and anticonvulsant activities of ethanol fraction from Rhizoma Pinelliae Praeparatum (EFRP) and to determine whether these effects were related to GABAergic mechanism.

Materials and methods

The sedative, hypnotic and anticonvulsant activities of EFRP were investigated with locomotion activity, pentobarbital-induced sleeping and nikethamide (NKTM)-induced convulsion tests, respectively. Additionally, the effects of flumazenil (an antagonist of GABA_A receptor) and l-malic acid (blocker of synthetic enzyme for GABA) on the hypnotic activity of EFRP were evaluated.

Results

EFRP at dose of 12 g/kg significantly inhibited the locomotion activity of mice. EFRP showed synergic effect on pentobarbital-induced sleeping by increased numbers of mice falling asleep, reduced the sleep latency and prolonged the sleeping time. l-malic acid and flumazenil inhibited the augment effects of EFRP on pentobarbital-induced sleeping. EFRP promoted a significant protection to NKTM-induced convulsion, by prolonged the death latency and decreased mortality.

Conclusion

EFRP possessed sedative, hypnotic and anticonvulsant activities and these activities may be related to the GABAergic system.     

Anticonvulsant activity of DNS II fraction in the acute seizure models

Aim of the study

Delphinium nordhagenii belongs to family Ranunculaceae, it is widely found in tropical areas of Pakistan. Other species of Delphinium are reported as anticonvulsant and are traditionally used in the treatment of epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii was subjected to bioassay-guided fractionation and the most active fraction, i.e. DNS II acetone was chosen for further testing in the acute seizure models of epilepsy to study the antiepileptic potential in male mice.

Materials and methods

Different doses (60, 65 and 70 mg/kg, i.p.) of DNS II acetone fraction of Delphinium nordhagenii was administered 30 min prior the chemoconvulsant's injection in the male mice. Convulsive doses of chemoconvulsants (pentylenetetrazole 90 mg/kg, s.c. and picrotoxin 3.15 mg/kg, s.c.) were used. The mice were observed 45–90 min for the presence of seizures. Moreover, four different doses of DNS II (60, 65, 70 and 100 mg/kg, i.p.) were tested in the MES test.

Results

The DNS II acetone fraction of Delphinium nordhagenii has exhibited the anticonvulsant actions by preventing the seizures against PTZ- and picrotoxin-induced seizure as well as 100% seizure protection in MES test. The results are comparable with standard AEDs (diazepam 7.5 mg/kg, i.p. and phenytoin 20 mg/kg, i.p.).

Conclusions

These findings suggest that the Delphinium nordhagenii possesses the anticonvulsant activity. Further analysis is needed to confirm the structure and target the extended activity profile.     

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.