Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae)

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl-D-aspartate-induced turning behavior. The ED(50) for protection against seizures was 306 (154-541) mg/kg intraperitoneally (i.p.) for the PTZ test and 1005 (797-1200) mg/kg i.p. for the MES test. The ED(50) of methanolic extract against N-methyl-D-aspartate-induced turning behavior was 875 (623-1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54% of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties in animals that might explain its use as a traditional medicine for epilepsy in Africa.     

Differential effects of three species of Hypericum in an open field test

The effects of three species of Hypericum (H.) on mice motor activity were compared in an automated open field test. Methanol extracts of H. perforatum L., H. hircinum L. and H. perfoliatum L. were tested at doses ranging from 2.5 to 200 mg i.p. H. hircinum decreased locomotion at most dose levels. Moreover, a dose of 200 mg/kg of all three herbal species sharply decreased motor activity. Ten mg/kg of H. perforatum, a dose that is comparable to that endowed with antidepressant effects in humans, tended to increase exploration and stereotypic activity and to decrease immobility. The study suggests that there are differences in the neuropharmacological actions of the three plant extracts. However, common constituents might explain the reduced motor activity observed at high dose levels.     

Effect of Hypericum perforatum on marble-burying by mice

The effect of Hypericum perforatum extract (LI 160) at a dose that exerts an antidepressive-like effect was studied in mice in the marble-burying test. Acute Hypericum perforatum (150, 300 and 500 mg/kg, p.o.) reduced immobility time in the forced swimming test. The number of marbles buried, but not locomotor activity, was reduced by acute treatment with Hypericum perforatum (150 and 300 mg/kg, p.o.). However, this effect was not seen after chronic treatment (21 days) with Hypericum perforatum (300 mg/kg, p.o.). Thus, Hypericum perforatum extract, at antidepressant dose, exerts an acute anxiolytic drug effect on the marble-burying test, which could indicate a potential anti-obsessive effect, although the development of tolerance could be an important drawback.     

Anticonvulsant activity of Heracleum persicum seed

The anticonvulsant activity of acetone extract of the seeds of Heracleum persicum (Umbelliferae) was examined against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice. The extract showed a dose-dependent protective effect in both seizure models. However, the sedative dose of the extract, examined by rotarod test, was close to the anticonvulsant doses. Preliminary phytochemical analysis showed the presence of alkaloids, terpenoids, triterpenes and steroids in the extract. The observed pharmacological effects could be due to alkaloids, terpenoids and triterpenes present in the plant.     

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.     

Antiinflammatory activity of ethanol extracts of Hypericum perforatum L., H. barbatum Jacq., H. hirsutum L., H. richeri Vill. and H. androsaemum L. in rats

Ethanol extracts of the aerial parts of six Hypericum species, H. barbatum, H. androsaemum, H. richerii, H. hirsutum, H. perforatum and H. perforatum cultivated on mountain Tara were tested for antiinflammatory activity in comparison with indomethacin (IND) using the carrageenan-induced rat paw edema test. It was found that all examined extracts produced antiinflammatory activity, particularly those from H. hirsutum, and both wild and cultivated H. perforatum. A dose-dependent antiinflammatory effect was especially pronounced in extracts showing some lower antiinflammatory activity. There was no correlation between the amount of hypericin in the extracts and their antiinflammatory activity. Copyright (c) 2006 John Wiley & Sons, Ltd.     

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.     

Antidepressant effects of the methanol extract of several Hypericum species from the Canary Islands.

The aim of the present study was to investigate several neuropharmacological effects of the methanol extract of the aerial parts in blossom of Hypericum canariense, H. glandulosum, H. grandifolium and H. reflexum (Hypericaceae). These extracts did not alter significantly the locomotor activity, body temperature or the pentobarbital-induced sleeping time, with the exception of H. reflexum which significantly potentiated pentobarbital-induced sleeping time at both doses assayed (500 and 1000 mg/kg p.o.). Additionally, neither muscle relaxant nor anticholinergic activity was observed. These extracts antagonized the ptosis and/or motor depression induced by tetrabenazine and also shortened the immobility time in the forced swimming test. Moreover, the H. glandulosum and H. grandifolium extracts at 1000 mg/kg p.o. potentiated the head twitches induced by 5-HTP. These observations suggest that the methanol extract of the Hypericum species in doses of 500-1000 mg/kg p.o. possess antidepressant activity in mice, without inducing significant muscle relaxation, anticholinergic and sedative properties.     

Effect of Curcumin Against Pentylenetetrazol‐Induced Seizure Threshold in Mice: Possible Involvement of Adenosine A1 Receptors

Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20–120 mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80 mg/kg) was prevented by 8‐phenyltheophylline (0.5 mg/kg, i.p., non‐selective adenosine receptor antagonist) and 8‐cyclopentyl‐1,3‐dipropylxanthine (5 mg/kg, i.p., adenosine A₁ receptor antagonist) but not by 8‐(3‐cholorostryl)caffeine (4 mg/kg, i.p., adenosine A_2A receptor antagonist). Further, 5′‐N‐ethylcarboxamidoadenosine (0.005 mg/kg, i.p., non‐selective A₁/A₂ receptor agonist), or N⁶‐cyclohexyladenosine (0.2 mg/kg, i.p., adenosine A₁ receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5′‐(N‐cyclopropyl) carboxamidoadenosine (0.1 mg/kg, i.p., adenosine A_2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A₁ but not A_2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions. Copyright © 2013 John Wiley & Sons, Ltd.     

Anticonvulsant Effect of Berberis integerrima L. Root Extracts in Mice

Berberis integerrima is a member of Berberidaceae family. Berberine is one of the main constituents of this plant, having neuroprotective effect on central nervous system diseases. In this study, the anticonvulsant activity of methanolic extract, and hydromethanolic fraction, and chloroform fraction of B integerrima was assessed. The anticonvulsant effect of B integerrima was investigated using both pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizure models. The LD50 value of the methanolic extract was 302.676 mg/kg. In the PTZ test, methanolic extract (140 and 200 mg/kg, i.p., p < 0.01), hydromethanolic fraction (200 mg/kg, p < 0.01), and chloroform fraction (200 mg/kg, p < 0.01) increased the onset time of hind limb tonic extensions (HLTEs). The protective effect against mortality (convulsion survivors/animals tested) was 2/8 in methanolic extract, and 3/8 in hydromethanolic fraction at a dose of 200 mg/kg and in chloroform fraction at a dose of 140 mg/kg. In the MES test, this plant did not display any significant effect in reducing HLTE duration. According to phytochemical screening, methanolic extract contained alkaloids and tannins. The present study, conducted in mice, indicated that B integerrima has anticonvulsant activity in PTZ-induced seizures. It is concluded that B integerrima may be useful in petit mal epilepsy.     

Antidepressant properties of some Hypericum canariense L. and Hypericum glandulosum Ait. extracts in the forced swimming test in mice

It has been shown in a previous work that the methanol extract obtained from the aerial part in blossom of Hypericum canariense L. and Hypericum glandulosum Ait. was active in the tetrabenazine and forced swimming test. In the present study, the central nervous effect of the aqueous, butanol and chloroform fractions obtained from the methanol extracts of these Hypericum species was investigated in mice, particularly in animal models of depression. It was found that the immobility time in the forced swimming test was significantly reduced by the butanol and chloroform fraction of both species assayed, producing no effects or only a slight depression on spontaneous motor activity when assessed in a photocell activity meter. In this regard, the efficacy of the chloroform extract from Hypericum glandulosum Ait. (500 mg/kg p.o.) in the forced swimming test was comparable to that of the tricyclic antidepressant imipramine (50 mg/kg p.o.). In addition, the Hypericum glandulosum chloroform fraction was also effective in antagonizing the ptosis induced by tetrabenazine. Moreover, Hypericum canariense butanol fraction and Hypericum glandulosum chloroform fraction produced a slight but significant hypothermia. Taken together, these data demonstrate that the butanol and chloroform fractions from Hypericum canariense and Hypericum glandulosum possess antidepressant-like effects in mice, providing further support for the traditional use of these plants in the Canary Islands folk medicine against central nervous disorders.     

Anticonvulsant effect of Persea americana Mill (Lauraceae) (Avocado) leaf aqueous extract in mice

Various morphological parts of Persea americana Mill (Lauraceae) (avocado) are widely used in African traditional medicines for the treatment, management and/or control of a variety of human ailments, including childhood convulsions and epilepsy. This study examined the anticonvulsant effect of the plant's leaf aqueous extract (PAE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Like the reference anticonvulsant agents used, Persea americana leaf aqueous extract (PAE, 100-800 mg/kg i.p.) significantly (p < 0.05-0.001) delayed the onset of, and antagonized, pentylenetetrazole (PTZ)-induced seizures. The plant's leaf extract (PAE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but only weakly antagonized bicuculline (BCL)-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that 'avocado' leaf aqueous extract (PAE) produces its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain. The findings of this study indicate that Persea americana leaf aqueous extract possesses an anticonvulsant property, and thus lends pharmacological credence to the suggested ethnomedical uses of the plant in the management of childhood convulsions and epilepsy.     

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.     

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.     

Effect of Rosmarinus officinalis L. aerial parts extract on morphine withdrawal syndrome in mice

The effect the aqueous and ethanol extracts of Rosmarinus officinalis L. aerial parts on morphine withdrawal syndrome was investigated in mice. The aqueous and ethanol extracts induced a significant antinociceptive activity in the writhing test. This activity was inhibited by naloxone pretreatment. Dependence was induced using subcutaneous injections of morphine daily for 3 days. On day 4, morphine was injected 2 h prior to the intraperitoneal injection of naloxone. The number of jumps during the 30 min period after naloxone injection was considered as a measure of the withdrawal syndrome. The results indicated that the aqueous (1.68 g/kg and 2.4 g/kg, i.p.) and ethanol (0.96 g/kg, i.p.) extracts reduced the number of jumps. Phytochemical study indicated that only the aqueous extract of R. officinalis has an alkaloid component. It is concluded that the aqueous and ethanol extracts of R. officinalis aerial parts could diminish morphine withdrawal syndrome.     

Anticonvulsant activities of the FS-1 subfraction isolated from roots of Delphinium denudatum

Delphinium denudatum Wall. (Ranunculaceae) is a medicinal herb used for the treatment of epilepsy in the subcontinent. The present study reports the anticonvulsant activities in the maximal electroshock test (MEST) and subcutaneous pentylenetetrazole (PTZ), bicuculline (BIC), picrotoxin (PIC)-induced seizures of the FS-1 subfraction (FS-1) that was obtained by purification of an aqueous fraction isolated from the roots of D. denudatum. In CF 1 mice, FS-1 (600 mg/kg i.p.) exhibited very potent anticonvulsant activity that was comparable to the effects of the well-known antiepileptic drug phenytoin (20 mg/kg) in MEST and protected 100% animals from hind limb tonic extension phase of this model. FS-1 also suppressed PTZ-induced threshold seizure and the loss of the righting reflex with tonic fore and hind limb extension by 100%, similar to the antiepileptic drug valproic acid (350 mg/kg). BIC-induced seizures were suppressed in 80% of the animals. FS-1 exhibited weak anticonvulsant effect on PIC-induced seizures, however, it significantly reduced mortality and delayed the onset of seizures. FS-1 had no effect on strychnine (STN)-induced extensor seizures. The results demonstrate the broad and potent anticonvulsant activity of the compounds in FS-1 of D. denudatum.     

三种贯叶连翘组药用植物醇提物对小鼠的抗抑郁作用

目的：对贯叶连翘组药用植物的抗抑郁作用进行研究，为筛选新的药用品种以及对其品质评价提供药效学依据。方法：采用小鼠尾悬挂试验，小鼠强迫游泳试验抑郁模型对三种贯叶连翘组药用植物醇提物的抗抑郁作用进行研究。结果：在小鼠尾悬挂试验，小鼠强迫游泳试验中，元宝草和扬子小连翘醇提物物与贯叶连翘一样，可以对抗小鼠的失望行为，使实验动物的绝望时间（不动时间）缩短，具有抗抑郁作用，但是贯叶连翘醇提物的抗抑郁作用明显强于扬子小连翘。结论：三种川产贯叶连翘组药用植物醇提物在行为绝望动物模型上有明显的抗抑郁作用。     

Evaluation of sedative and anticonvulsant activities of Unmadnashak Ghrita

'Unmadnashak Ghrita' (UG) is a ayurvedic formulation containing Ferula narthex (6 g), Gardenia gummifera (6 g), Ellataria cardamom (6 g), Bacopa monneri (6 g), and cow's ghee (clarified butter fat) (76 g). In the present study, neuropharmacological activities of UG were evaluated for its gross behavioural effect, pentobarbitone sleeping time, spontaneous locomotor activity, antagonism to amphetamine induced hyperlocomotor activity, analgesic activity by tail flick test, rota-rod performance (motor coordination test), maximal electroshock (MES) induced seizures, and pentylenetetrazol (PTZ) induced convulsions in mice. The formulation showed CNS-depressant activity in gross behavioural test, potentiated pentobarbitone sleeping time and there was significant decrease in spontaneous locomotor count in mice. The formulation also antagonized the behavioral effects of CNS-stimulant drug amphetamine, and showed analgesic effect in mice. UG failed to affect the motor coordination test. The formulation also protected mice from MES and PTZ induced convulsions. These results suggest that UG has CNS-depressant and anticonvulsant activity in mice.     

Neuropharmacological profile of an ethanol extract of Ruta chalepensis L. in mice

The effects of an ethanol extract of the aerial parts of Ruta chalepensis on the central nervous system (CNS) and LD(50) determination were studied in mice. A crude extract was given systemically and its effects were tested on pentylenetetrazole (PTZ)-induced seizures, sodium pentobarbital-induced hypnosis, exploratory activity, anxiety and nociception. Results from the experimental models tested showed: (1) a delay in the onset of seizures and a dose-dependent suppression in the tonic phase and mortality induced by PTZ; (2) a prolongation of the time of sodium pentobarbital-induced hypnosis; (3) a significant attenuation in the anxiety-response and (4) a reduction in the licking time and shaking behavior in the formalin-induced nociception test. The sedative-hypnotic potentiation, anxiolytic, anticonvulsant and antinociceptive effects suggest that Ruta chalepensis induces a depressant activity on the CNS.     

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.