Pharmacological studies of the aqueous extract of Sapindus trifoliatus on central nervous system: possible antimigraine mechanisms

The aqueous extract of pericarp of fruits of Sapindus trifoliatus (ST) Linn., family Sapindaceae was evaluated for its potential effects on central nervous system in mice. The extract at doses 20 and 100 mg/kg, i.p. significantly (p < 0.001) reduced the spontaneous locomotor activity and at 100 mg/kg, increased the thiopental-induced sleeping time. In rota-rod motor co-ordination test, ST at 100 mg/kg, i.p. significantly (p < 0.05-0.01) reduced the endurance time. Further ST exhibited no protection against maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced convulsions in mice. In receptor radioligand binding studies, ST exhibited affinity towards dopaminergic, alpha-adrenergic and muscarnic receptors. The findings suggest that, ST may possess principles with potential neuroleptic properties.     

The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice.

This study investigates anticonvulsant effects of an essential oil of the fruits of Pimpinella anisum (Umbelliferae), a folkloric remedy in the Iranian traditional medicine, against seizures induced by pentylenetetrazole (PTZ) or maximal electroshock (MES) in male mice. The essential oil suppressed tonic convulsions induced by PTZ or MES. It also elevated the threshold of PTZ-induced clonic convulsions in mice. The essential oil produced motor impairment. However, this effect was not observed at the doses and time courses needed for anticonvulsant activity.     

Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice

In this study, the effect of an essential oil of Eugenia caryophyllata (Myrtaceae), an antiepileptic remedy in Iranian folk medicine, against seizures induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in male mice was studied. The essential oil exhibited anticonvulsant activity against tonic seizures induced by MES. Although it was not effective against clonic convulsions induced by intraperitoneal administration of PTZ, the seizure threshold which was determined by an increase in the dose of intravenously infused PTZ required to induce clonus, was elevated by the essential oil. In addition, at some anticonvulsant doses, the essential oil produced motor impairment on the rotarod.     

Pharmacological activities investigation of crude extracts and fractions from Qualea grandiflora Mart

This study investigates pharmacological activities of crude hydroalcoholic extract and fractions of Qualea grandiflora Mart. leaves employing different experimental models using mice. The treatment with crude hydroalcoholic extract (EH) in a dose of 500 mg/kg, i.p. caused: signs of central nervous system depressant action in the Hippocratic screening test, confirmed by the potentiation of sodium pentobarbital sleeping time. Increasing in the latency time of hot plate assay that indicate an analgesic effect; significantly delaying of the onset of clonic PTZ convulsions, increasing in the time for death, suppressing of the tonic PTZ convulsion, and decreasing of severity and number of convulsions. The median lethal dose of EH was 1.321 mg/kg. The convulsions induced by PTZ, ethyl ether fraction (300 mg/kg, i.p.) was more active in increasing the latency time for first convulsion, moreover, the hexane fraction, at the same dose, was more active in increasing the time for death and/or avoiding the death. Both did not cause disturbance in motor coordination at the dose of 500 mg/kg, assessed by rotarod test. These results suggest that the crude extract of leaves of Qualea grandiflora Mart. has a central nervous system depressant action, an analgesic effect and behave as a potential anticonvulsant.     

Effects of extract of Cistus populifolius L. on the central nervous system.

We report the effects on the central nervous system (CNS) and on analgesic activity of an aqueous extract of Cistus populifolius L. The extract was assayed for effects on spontaneous locomotor activity, methylphenidate-induced hypermotility, motor coordination, exploratory behaviour, rectal temperature and sodium pentobarbital-induced hypnosis. Analgesic activity was evaluated using the hot plate test. The C. populifolius extract at dosages of 286 and 430 mg/kg caused very significant reductions in spontaneous locomotor activity, hypermotility, motor coordination, exploratory behaviour and rectal temperature, and a slight increase of sleeping time was noted in the sodium pentobarbital-induced sleep test. The extract exhibited central analgesic affects in the hot plate test.     

Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus tatarinowii on mice and rats

This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)‐induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium‐induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma‐aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABA_A, Bcl‐2, and caspase‐3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl‐2 were up‐regulated by treating with eudesmin, whereas the caspase‐3 obviously was down‐regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up‐regulation of GABA_A and GAD65 expressions, and anti‐apoptosis of neuron the in brain. Copyright © 2015 John Wiley & Sons, Ltd.     

Psychopharmacological profiles of Leucas Lavandulaefolia Rees

Methanol extract of Leucas lavandulaefolia (LLFE) was evaluated for different psychopharmacological profiles with various animal models in rats and mice. The extract showed a potential reduction in spontaneous activity and caused a significant decrease in exploratory behavioural pattern by the head dip and Y-maze test. It also showed a significant reduction in muscle relaxant activity by rotarod, 30 degrees inclined screen and traction tests. The extract showed a remarkable potentiation of pentobarbitone induced sleeping time in mice.     

Anticonvulsant effect of Hypericum perforatum: role of nitric oxide

Hypericum perforatum L. is used in traditional medicine for its anticonvulsant property. We studied the anticonvulsant activity of the aqueous and ethanolic extracts of Hypericum perforatum aerial parts in mice in order to evaluate the traditional use of this plant. The pentylenetetrazole (PTZ) and the maximal electroshock seizure (MES) tests were used for assessing the anticonvulsive effects of this plant. In the PTZ test, the extracts (0.1-1g/kg, i.p.) delayed the onset of tonic convulsions and protected mice against mortality. In the MES test, both extracts did not showed an antiseizure activity. L-NAME (1-10 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, reduced the anticonvulsant activity of the extracts. The results of this study indicate that the extracts of Hypericum perforatum aerial parts could contribute to the control of petit mal seizure and this effect may be partially mediated by nitric oxide pathway.     

Evaluation of the central properties of several Hypericum species from the Canary Islands

The infusions of the aerial parts in blossom of Hypericum canariense, H. glandulosum, H. reflexum and H. grandifolium (Hypericaceae) were evaluated for their pharmacological activity on the central nervous system in mice using various behavioural models including locomotor and muscle relaxant activity, effect on normal body temperature, pentobarbital-induced sleep, oxotremorine and tetrabenazine-induced syndrome, apomorphine-induced hypothermia and 5-hydroxytryptophan-induced head twitches, as well as a forced swimming test. These infusions did not alter significantly the locomotor activity, pentobarbital induced sleeping time and body temperature, with the exception of H. canariense which produced a slight but significant hypothermia. Additionally, no muscle relaxant or anticholinergic activity were observed. These infusions antagonized the ptosis and/or motor depression induced by tetrabenazine as well as shortening the immobility time in the forced swimming test. The observations suggest that the infusions of these Hypericum species possess antidepressant activity in mice, without inducing muscle relaxation, anticholinergic and sedative properties.     

Effects of the gut-stimulating principle in Croton penduliflorus seed oil on the central nervous system

The gut-stimulating principle in Croton penduliflorus seed oil isolated as white crystals (CP crystals) significantly reduced pentobarbitone-induced sleeping time in mice at doses of 3 and 6 mg/kg intraperitoneally. Indomethacin (4 mg/kg) and atropine (0.044 mg/kg) significantly reversed the action of CP crystals on pentobarbitone sleeping time with indomethacin having a profound reversal effect. CP crystals significantly reduced the mean onset of convulsions and the mean death time in mice treated with a surely convulsive dose of strychnine. CP crystals significantly reduced the intensity of morphine and pethidine analgesia and prolonged the duration of pethidine analgesia. Most actions of CP crystals suggest that it stimulates the CNS and reduces the intensity of opioids (except codeine) while prolonging their duration of analgesic action.     

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.     

CNS inhibitory effects of barakol,a constituent of Cassia siamia Lamk

The present study determined the pharmacological profile of barakol, a major constituent of Cassia siamea Lamk., in rodent behavioral and neurochemical tests. Barakol reduced spontaneous locomotor activity, increased the number of sleeping animals and prolonged the thiopental-induced sleeping time, indicating a sedative effect. As for interactions between barakol and convulsants (pentylenetetrazole (PTZ), picrotoxin, bicuculline and strychnine), only a high dose (100 mg/kg, i.p.) of barakol slightly prolonged the latency of clonic convulsion induced by picrotoxin. This suggests that the sedative effect may not be induced via the GABA or glycine systems. There was no evidence of an anxiolytic effect of barakol in the plus-maze test. However, barakol (25-100 mg/kg, i.p.) could suppress methamphetamine (1 mg/kg, i.p.)-induced hyper-locomotor activity in a dose-dependent manner, indicating an effect on the dopaminergic system. In a microdialysis study, the dose of barakol (100 mg/kg) that inhibited spontaneous locomotor activity in mice did not affect the basal levels of extracellular dopamine (DA) or its metabolites in the striatum. However, pretreatment with barakol (100 mg/kg, i.p.) decreased the maximal dopamine release and dopamine turnover induced by methamphetamine (1 mg/kg, i.p.). This finding indicates that the inhibitory effect of barakol on dopamine release may account for the blocking effect of barakol on the striatum-related behavior induced by methamphetamine.     

Psychopharmacological effects of the essential oil fraction and of the hydrolate obtained from the seeds of Licaria puchury-major

An essential oil fraction obtained from powdered seeds of Licaria puchury-major contained 51.3% of safrol, 3.3% of eugenol and 2.9% of methyleugenol, among other substances. Fifty to 800 mg/kg of this fraction reduced motor activity and anesthetized mice; it also protected the animals against transcorneal electroshock. A hydrolate obtained from the powder, contained 0.2 mg of essential oil fraction per ml: 0.1 and 0.2 ml/10 g of this hydrolate reduced motor activity and potentiated barbiturate sleeping time of mice; 2.5-10 ml/kg given to rats produced a drop in body temperature. The hydrolate, however, did not anesthetize and did not protect mice against convulsions induced by electrical shock. These amounts of the hydrolate corresponded to dosing the animals with 2-4 mg/kg of the essential oil (or 1-2 mg/kg of safrol), doses which were inactive per se. This suggested that the pharmacological activity of the hydrolate was not due to its essential oil content. Corroborating this possibility the hydrosoluble portion of the hydrolate mimicked all of its effects: reduced motor activity, potentiated barbiturate sleeping time of mice and decreased body temperature of rats. The hydrosoluble material, as the hydrolate, was also incapable of anesthetizing and protecting mice against electroshock induced convulsions.     

Neuropharmacological screening of Diospyros mespiliformis in mice

The neuropharmacological activities of the aqueous extract of Diospyros mespiliformis stem bark were screened in mice. The extracts effect on pentobarbital-induced sleeping time, pentylenetetrazole induced seizure, spontaneous motor activity (SMA), exploratory behaviour, and rota-rod performance (motor coordination) were evaluated. The extract (100 and 200 mg/kg p.o.) produced a significant (P<0.05) prolongation of pentobarbital-induced sleeping time, and reduced the SMA and exploratory behaviour. The extract prolonged onset of the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. It also failed to affect the motor coordination test. These results suggest that the extract contained an agent with neuropharmacological activity that may be sedative in nature.     

Effect of Chinese herbal medicine "kanbaku-taiso-to" on neuropharmacological tests

The "Kanbaku-taiso-to" (KT), mixture of three herbal drugs, Glycyrrhizae Radix, Tritici Semen and Zizyphi Fructus, sometimes shows a marked effect on insomnia and infantile convulsions. The ancient Chinese medical book "Kinkiyoryaku" described the effectiveness of KT on emotional irritability. To elucidate the mechanism of action of KT, neuropharmacological screening tests were performed and the following results were obtained. KT lengthened the hexobarbital sleeping time; KT showed a marked prolongation of time to death in pentylenetetrazole (PTZ)-induced convulsions; locomotor activity was inhibited by 7-day continuous administration of KT. These results suggested that KT had a sedative effect on the nervous system.     

Neuropharmacologial effects of Cystoseira usneoides extract

The effects were studied of an extract of the brown algae Cystoseira usneoides on the central nervous system (CNS) of mice. At doses between 6.25 and 25 mg/kg the extract had significant effects on spontaneous locomotor activity, exploratory behaviour, D-amphetamine-induced hypermotility, body temperature, pentobarbitalinduced hypnosis, motor coordination and pentylenetetrazole-induced convulsions. Dopamine, 3,4-dihydroxy-phenylacetic acid, 3-methoxytyramine and homovanilic acid levels were determined in rat striatum and they were slightly modified. The extract also displayed analgesic activity. We conclude that the extract of Cystoseira usneoides is a CNS depressant with slight analgesic effects.     

九子参总皂甙药理研究

研究九子参总皂甙对小鼠中枢神经系统的作用。光电法测定小鼠自发活动,戊巴比妥钠用于观察协同作用,戊四氮电休克法研究抗惊厥作用,热板法测定镇痛作用。结果表明九子参总甙属皂甙类,对中枢神经系统有抑制作用,可减少小鼠自发活动,协同戊巴比妥催眠并有一定的镇痛作用,无对抗戊四氮和电休克惊厥作用,还能提高小鼠的耐缺氧能力,小鼠灌胃的ＬＤ５０为１．６５ｇ／ｋｇ。     

Neuropharmacological activity of Solanum nigrum fruit

The ethanol extract of the fruit of Solanum nigrum L. (Solanaceae) was studied for its neuropharmacological properties on experimental animals. On intraperitoneal injection, the extract significantly prolonged pentobarbital-induced sleeping time, produced alteration in the general behavior pattern, reduced exploratory behavior pattern, suppressed the aggressive behavior, affected locomotor activity and reduced spontaneous motility. The observations suggest that the fruit of S. nigrum possesses potential CNS-depressant action.     

Neuropharmacological activity of Eupatorium buniifolium aqueous extract in mice

The aim of this study was to evaluate the neuropharmacological profile of the Eupatorium buniifolium aqueous extract (EB) in mice. EB at doses up to 1.5 g/kg p.o. of the lyophilized material produced a dose dependent sleep induction and potentiation of sub-hypnotic and hypnotic doses of pentobarbital, respectively. However, EB neither modified the spontaneous motor activity nor produced a myorelaxant effect. Moreover, EB 1.5 g/kg in a nose-poke habituation task, produced a disruption of the normal patterns of habituation, and in a step-down inhibitory avoidance task, induced an amnesic effect similar to diazepam. These results suggest that the activity of EB may be a CNS-depressant.     

Sedative and anticonvulsant activities of the aqueous root extract of Sanseviera liberica Gerome & Labroy (Agavaceae)

The central nervous system (CNS) depressant and anticonvulsant activities of the aqueous root extract of Sanseviera liberica (ASL) were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behaviour for sedation tests, and strychnine, picrotoxin, bicuculline and pentylenetetrazole-induced convulsions in mice. ASL (100-400mg/kg, p.o.), like chlorpromazine HCl (1mg/kg, i.m.), produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behaviour. ASL (100 and 200mg/kg) produced dose-dependent and significant (P<0.05) increases in onset to clonic and tonic convulsions, and at 400mg/kg, showed complete protection against seizures induced by strychnine, picrotoxin and bicuculline, but not with pentylenetetrazole. ASL up to 10 g/kg, p.o. did not produce death, but i.p. treatment produced mortalities with LD(50) of 668.3+/-47.6 mg/kg. Preliminary phytochemical investigations of ASL revealed the presence of carbohydrates, alkaloids, saponins, reducing sugars and oils. The results indicate that ASL has sedative and anticonvulsant activities, therefore, justifying its use in traditional African medicine.