Anticonvulsant activity of Benkara malabarica (Linn.) root extract: In vitro and in vivo investigation

Aim of the study

To systematically investigate the anticonvulsant activity of methanol extract of Benkara malabarica roots and to provide a biochemical basis elucidating its mode of action.

Methods

The median lethal dose (LD₅₀) of Benkara malabarica extract was determined. The anticonvulsant activity of the extract was assessed in strychnine-induced and isoniazide-induced convulsion models; phenytoin (20 mg/kg) and diazepam (1 mg/kg) were used as standards, respectively. Percentage protection provided by the drug was accounted as decrease in the number of convulsions within 8 h of observation. Mechanism of action was studied by performing GABA transaminase (GABA-T) assay, isolated from rat brain. Active constituent was isolated and characterized from the plant extract.

Results

The median lethal dose (LD50) of Benkara malabarica was found to be more than 500 mg/kg. It demonstrated 30% and 35% protection against strychnine-induced convulsions and 60% and 80% protection against isoniazide-induced convulsions, at doses of 25 mg/kg and 50 mg/kg, respectively. Enzyme assay results revealed that Benkara malabarica extract possesses GABA-T inhibitory activity (IC50 = 0.721 mg/ml). Scopoletin which was identified as the major constituent of the extract was found to be an inhibitor of GABA-T (IC50 = 10.57 μM).

Conclusions

The anticonvulsant activity of the plant extract is predominantly GABA mediated and may be due to the action of scopoletin alone or is a result of synergy of different compounds in the extract in which scopoletin is the major constituent.     

Diuretic effect of the crude extracts of Carissa edulis in rats

Carissa edulis (forssk) vahl (Apocynaceae) is used traditionally for the treatment of headache, chest complaints, rheumatism, gonorrhoea, syphilis, rabies and as a diuretic. In the present study, the diuretic activity of different extracts of Carissa edulis was investigated. The diuretic activity of the different extracts of Carissa edulis in a dose range of 50-1000 mg/kg was assessed orally in rats using hydrochlorothiazide as a standard drug. The root bark maceration extract showed no effect on the urine output up to a dose of 1000 mg/kg, while the root bark soxhlet extract produced a significant increase (P < 0.05) in urine output at a dose of 1000 mg/kg. The root wood maceration and root wood soxhlet extracts produced a significant increase in urine output at a dose of 50 mg/kg, with a P-value of <0.05. Urinary electrolyte excretion was also affected by the extracts: the root bark soxhlet extract increased urinary excretion of sodium, potassium and chloride ions; root wood maceration extract increased excretion of sodium and potassium, while root wood soxhlet extract increased excretion of potassium ion. These findings support the traditional use of Carissa edulis as a diuretic agent.     

Anticonvulsant activity of the methanolic extract of Justicia extensa T. Anders

Ethnopharmacological relevance

To investigate the anticonvulsant activity of the leaf extract of Justicia extensa T. Anders used traditionally in the treatment of convulsion.

Materials and methods

The anticonvulsant activity of the methanolic extract of Justicia extensa (50, 100 and 200 mg/kg, p.o.) was assessed in strychnine-induced (STR) and picrotoxin-induced (PCT) convulsion models in mice. Diazepam (1 mg/kg) and phenobarbitone (2 mg/kg) were used as reference drugs respectively.

Results

The extract showed no toxicity and significantly prolonged (p < 0.01-0.05) the onset and reduced the duration of the seizures induced by picrotoxin (5 mg/kg, i.p.) in a dose dependent manner. Phenobarbitone completely inhibited the seizures in this model. Similarly, in the seizures induced by strychnine (1 mg/kg, i.p.), the extract also prolonged the onset and reduced the duration of the seizures though not in a dose dependent manner. Diazepam failed to inhibit the strychnine-induced seizures. The plant extract however showed a significantly higher anticonvulsant activity at 100 and 200 mg/kg in comparison with diazepam.

Conclusions

The results obtained from this work suggest that Justicia extensa has anticonvulsant activity and this supports the use of the plant traditionally in the treatment of convulsion.     

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

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

Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model

The popular medicine Passiflora edulis has been used as a sedative, tranquilizer, against cutaneous inflammatory diseases and intermittent fever. Most of the pharmacological investigations of Passiflora edulis have been addressed to its Central Nervous System activities, such as anxiolytic, anticonvulsant and sedative actions. Otherwise, there are few reports about the anti-inflammatory activity of the Passiflora species. The aim of this study was to investigate the mechanism of the anti-inflammatory effect of aqueous lyophilized extract obtained from leaves of Passiflora edulis var. flavicarpa Degener (Passifloraceae) in the mouse model of pleurisy induced by carrageenan (Cg), bradykinin, histamine or substance P, observing the effects upon leucocytes migration, myeloperoxidase (MPO), nitric oxide (NO) concentrations and tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1beta) levels. RESULTS: Passiflora edulis (250mg/kg) administered by intraperitoneal route (i.p.) inhibited the leukocyte, neutrophils, myeloperoxidase, nitric oxide, TNFalpha and IL-1beta levels (P<0.01) in the pleurisy induced by carrageenan. Passiflora edulis (250-500mg/kg, i.p.) also inhibited total and differential leukocytes in the pleurisy induced by bradykinin, histamine or substance P (P<0.05). CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines (TNFalpha, IL-1beta), enzyme (myeloperoxidase) and mediators (bradykinin, histamine, substance P, nitric oxide) release and/or action, appear to account for Passiflora edulis's actions.     

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 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.     

Antidepressant activity of standardised extract of Marsilea minuta Linn

AIM OF THE STUDY: Marsilea minuta Linn. (Marsileaceae) has been referred in Indian traditional medicine system (Ayurveda) for the treatment of insomnia and other mental disorders. Marsiline isolated from Marsilea minuta was reported to have sedative and anticonvulsant property. The ethanol extract of Marsilea minuta was standardised for marsiline (1.15%, w/w) and studied for its antidepressant activity. MATERIALS AND METHODS: Antidepressant activity was studied using forced swimming test (FST), tail suspension test (TST), learned helplessness test (LHT) and 5-hydroxytryptophan (5-HTP) induced head twitches response in rodents. Standardised extract of Marsilea minuta in doses of 100, 200 and 400 mg/kg/day were administered orally for three consecutive days and evaluated on day 3, 1h after the last dose treatment. Imipramine (15 mg/kg/day, i.p.) was used as the standard drug. Neurochemical mechanism of antidepressant activity was elucidated by using radioligand receptor binding assays for 5-HT2A and benzodiazepine receptors in rat frontal cortex. RESULTS: Immobility time in FST and TST was significantly (P<0.05) reduced by ethanol extract of Marsilea minuta treated animals. A decrease in number of escape failures in LHT was also observed in Marsilea minuta treated rats. Head twitch response induced by 5-HTP was significantly attenuated by Marsilea minuta (400 mg/kg, p.o.) and imipramine showing the involvement of serotonergic system. This effect was corroborated with radioligand receptor binding study where Marsilea minuta (400 mg/kg, p.o.) significantly (P<0.05) down regulated 5-HT2A receptor in frontal cortex, whereas, no marked effect was observed for benzodiazepine receptor. CONCLUSION: The antidepressant effect exhibited by Marsilea minuta extract may be due to its effect on 5-HT2A density in rat frontal cortex.     

A pharmacological evaluation of Baphia nitida Lodd (Leguminosae) ethanolic extract on rats and mice

Fresh leaves of Baphia nitida supplied by a herbalist were extracted, screened phytochemically and then subjected to various pharmacological tests. The phytochemical tests showed the presence of saponin, flavonoid glycosides and true tannins. In the dose range used, no acute toxicity was observed for the ethanolic extract. The extract showed a dose dependent antinociceptive (analgesic) activity in mice with the analgesic activity of 500 mg/kg extract being comparable to that of 300 mg/kg of acetylsalicylic acid. The extract demonstrated an antidiarrhoeal effect by protecting rats against castor oil induced diarrhoea. This was also dose related but less than the protection afforded by sodium salicylate. The extract did not demonstrate any appreciable anticonvulsant effect against strychnine-induced convulsion in rats.     

Pharmacological basis for the medicinal use of Carissa carandas in constipation and diarrhea

Ethnopharmacological relevance

Carissa carandas Linn. commonly known as “Karaunda” (Apocynaceae) is a popular medicinal herb widely distributed in different parts of Pakistan. In addition to other medicinal uses, Carissa carandas is popular in indigenous system of medicine for its medicinal use in gut motility disorders like, constipation and diarrhea.

Objective

This study was planned to provide pharmacological basis to the medicinal use of Carissa carandas in constipation and diarrhea.

Materials and methods

The crude extract of the leaves of Carissa carandas (Cc.Cr) was prepared in methanol and its fractionation was carried out with ethylacetate, petroleum ether and n-butanol. In-vivo studies were conducted on mice, while isolated rabbit jejunum and guinea-pig ileum preparations were used for the in-vitro experiments. The spasmogenic and spasmolytic responses of gut tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.

Results

The HPLC fingerprints of Cc.Cr, its petroleum (Cc.Pef), ethylacetate (Cc.Eaf) and n-butanol (Cc.Baf) fractions showed the presence of oleanolic acid, ursolic acid, stigmasterol and β-sitosterol. Oral administration of Cc.Cr to mice increased fecal output at lower doses (30 and 50 mg/kg), while it showed protection against castor oil-induced diarrhea at higher doses (300 and 600 mg/kg). In isolated guinea-pig ileum and rabbit jejunum, Cc.Cr and Cc.Baf exhibited stimulatory effect at 0.003–3 mg/ml, which was partially sensitive to atropine or pyrillamine or partially/fully sensitive to atropine+pyrillamine, followed by relaxation at higher tested concentrations, being more potent in rabbit tissues. The ethylacetate fraction (0.1–5 mg/ml) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues, being more potent in guinea-pig while more efficacious in rabbit tissues. However, the petroleum fraction (0.003–1.0 mg/ml) showed only spasmolytic activity in spontaneously contracting rabbit tissues, similar to nifedipine. In guinea-tissue, Cc.Pef did not cause any stimulant effect. When studied against high K⁺ (80 mM)-induced contraction, the crude extract and its fractions caused a dose-dependent inhibition, with the following order of potency: Cc.Pef>Cc.Eaf>Cc.Cr≥Cc.Baf, similar to nifedipine indicating Ca⁺⁺ channel antagonist like activity, which was further confirmed when the plant extract displaced Ca⁺⁺ curves to the right with suppression of maximum effect similar to that of nifedipine.

Conclusion

This study demonstrates that the crude extract of Carissa carandas possesses a gut-stimulatory effect mediated primarily through the activation of muscarinic and histaminergic receptors while its spasmolytic effect was mediated possibly through Ca⁺⁺ antagonist pathway. Thus, this study provides a clear evidence for the dual effectiveness of Carissa carandas in constipation and diarrhea, thus validating its medicinal use.     

Anticonvulsant effect of Rhus chirindensis (Baker F.) (Anacardiaceae) stem-bark aqueous extract in mice

Extracts of Rhus chirindensis stem-bark are used extensively in South African traditional medicines for the treatment, management and/or control of an array of human ailments, including childhood convulsions and epilepsy. In this study, we investigated the anticonvulsant activity of the plant's stem-bark aqueous extract (RCE, 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. Single intraperitoneal injections of PTZ (90 mg/kg), PCT(10 mg/kg) or BCL (30 mg/kg) produced tonic-clonic seizures. Like the standard antiseizure drugs used, Rhus chirindensis stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) significantly delayed (p<0.05-0.001) the onset of, and antagonized pentylenetetrazole-induced seizures. The plant's stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin-induced seizures, but only weakly antagonized bicuculline-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that RCE produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results of this laboratory animal study indicate that RCE possesses anticonvulsant activity in the mammalian experimental model used, and thus suggest that the plant may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions and epilepsy. In conclusion, the findings of this study lend pharmacological credence to the suggested folkloric, ethnomedical uses of Rhus chirindensis in the management of childhood convulsions and epilepsy in some rural communities of South Africa.     

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.     

Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats

Plinia edulis, an arboreous species popularly known as "cambucá", is native to the Brazilian Atlantic Rain Forest. Despite its traditional uses, no reports are available on the safety of this utilization or on the relationship between the antiulcer activity of its extract and its phytochemical compounds. This paper reports on the investigation of the acute toxicity and gastroprotective effect of the aqueous ethanol extract of leaves of Plinia edulis on HCl/ethanol-induced ulcers. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to chromatographic fractionation after solvent partition. The extract did not show acute toxicity in mice treated with 5 g/kg p.o., but exhibited significant antiulcer activity in rats at doses of 100, 200, and 400mg/kg p.o., more active than the reference drug lansoprazole.The ethyl acetate fraction yielded beta-amyrin, oleanolic acid, ursolic acid, and maslinic acid, which were identified based on spectrometric analyses. Since antiulcerogenic activity is not restricted to one class of compounds in plants, the triterpenoids isolated in the extract can be associated with the observed effect.     

Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice

The anxiolytic and sedative effects of Tilia americana L. var. mexicana (Schltdl.) Hardin inflorescence extracts and its acute toxicity were tested. Sodium pentobarbital (SP)-induced hypnosis potentiation (SPP), as well as ambulatory activity and anti-anxiety response in three different experimental models were evaluated with hexane and methanol extracts in mice. In order to determine the proper timing of assessments and to identify the most active extract, a 100mg/kg dosage of hexane, ethyl acetate and methanol crude extracts were tested on SPP after 15, 30 and 60min of the administration. Then a dose-response curve was made for the hexane (10-1000mg/kg) and methanol (10-300mg/kg) extracts in all experimental models. Both extracts produced a significant and dose-dependent lengthening in the time of SP, with the methanol extract being more potent than the hexane extract at 60min after administration. Moreover, a significant and dose-dependent attenuation in the anxiety-response in the plus-maze test and exploratory cylinder activity, but also a diminution in the ambulatory activity and in the head dipping response were observed resembling the response to diazepam. Acute toxicity was observed with less dose of methanol extract (LD(50)=375mg/kg) in comparison to the hexane extract (LD(50)>2900mg/kg). Results of the present study shows that Tilia americana var. mexicana possesses depressant activity on the CNS similar to the better-studied species of European Tilia and reinforces its use as anxiolytic and sedative in traditional medicine.     

Anticonvulsant, analgesic and antipyretic activities of Taxus wallichiana Zucc

Taxus wallichiana Zucc. (Himalayan Yew) is often used in northern areas of Pakistan for the treatment of pyrexia, acute pains and epilepsy. We have investigated certain pharmacological activities of the methanol leaf extract against convulsion, nociception and pyrexia induced in rodents. The aim was to justify and explore its folk uses in these pathological conditions, on scientific basis. The studies were carried out using acetic acid-induced nociception and pentylenetetrazole-induced convulsions in mice, while formalin test and yeast-induced pyrexia in rats. Significant analgesic (67.77 and 74.29%) effect was found in acetic acid-induced model at doses of 100 and 200mg/kg, i.p. respectively. Crude extract exhibited significant (P<0.05) inhibition of the formalin noxious stimulation on both early and late phases of pain by the extracts (100 and 200mg/kg doses). In case of yeast-induced pyrexia model, 200mg/kg dose showed very significant (P<0.01) inhibition while 50 and 100mg/kg dose caused a significant (P<0.05) inhibition. Plant extract has controlled the pentylenetetrazole-induced convulsions in mice. 100 and 200mg/kg i.p doses of the extract significantly (P<0.05) inhibited the mioclonus and clonus while inhibition of tonus and hind limb tonic extension (HLTE) was highly significant (P<0.01). The anticonvulsant activity of this plant has been reported for the first time throughout the whole genus. The observed pharmacological activities provide the scientific basis for the folkloric use of the plant in treating epilepsy, pyrexia and acute pain.     

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.     

Anticonvulsant effect of aqueous extract of Valeriana officinalis in amygdala-kindled rats: Possible involvement of adenosine

Ethnopharmacological relevance

Valeriana officinalis L. (valerian) root extract has been used as an antiepileptic herbal medicine in Iran.

Aim of this study

In the present study the effect of valerian extracts on an experimental model of temporal lobe epilepsy (TLE) was evaluated. Moreover, the involvement of adenosine system in the actions of aqueous extract of valerian was evaluated.

Materials and methods

Bipolar stimulating and monopolar recording electrodes were implanted stereotaxically in the right basolateral amygdala of male Sprague–Dawley rats. After kindling, the effect of aqueous (200, 500 and 800 mg/kg; intraperitoneal) and petroleum ether (PE; 50 and 100 mg/kg; intraperitoneal) extracts of valerian and CPT (selective A₁ receptor antagonist; 10 and 20 μM; intracerebroventricular) on afterdischarge duration (ADD), duration of stage 5 seizure (S5D) and latency to the onset of bilateral forelimb clonuses (S4L) were measured. The effect of CPT (10 μM) on the response of aqueous extract of valerian (500 mg/kg) was also determined.

Results

The results showed that aqueous extract of valerian had anticonvulsant effect. However, PE extract and CPT (20 μM) had proconvulsant effect. Administration of CPT (10 μM) before the administration of aqueous extract decreased the anticonvulsant effect of valerian.

Conclusions

The results showed significant anticonvulsant effect for aqueous but not PE extract of valerian. Moreover, CPT as a selective adenosine A₁ receptor antagonist decreased the anticonvulsant effect of valerian aqueous extract. Therefore, we concluded that part of anticonvulsant effect of valerian probably is mediated through activation of adenosine 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.     

Casimiroa edulis seed extracts show anticonvulsive properties in rats

A single dose of 5, 10 and 100 mg/kg of Casimiroa edulis aqueous extract (AQ); 10, 100 and 1000 mg/kg of C. edulis ethanolic extract (E-OH); in addition, 10, 30 and 12 mg/kg of propyleneglycol (Pg), phenytoin (Phen) and phenobarbital (Phb) was orally given to adult male Wistar rat groups. Thereafter, all groups were assayed for protection against maximal electroshock (MES) and pentylenetetrazole (METsc) seizure inducing tests at hourly intervals throughout 8 h. For MES, a maximal protection of 70% at the 2nd and 4th h with 10 mg/kg AQ and 100 mg/kg E-OH doses, occurred. That of Phen, Phb and Pg was 80, 90 and 10% at the 8th, 6th and 2nd h, respectively. The averaged values of the MES unprotected rats under 10 and 100 mg/kg of AQ and E-OH extracts, showed that a shortened reflex duration as well as a delayed latency and uprising times occurred. On the other hand, just an enlarged latency and no protection against METsc device in AQ and EOH was observed. Phen and Phb maximal protection was 80 and 100% at the 4th and 6th hour against METsc. Thus, AQ is tenfold more potent anticonvulsive extract than E-OH against MES.     

Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae)

Aim of the study

Cocos nucifera cultivated in Brazil is known as “coco-da-Bahia” or “coqueiro-da-Índia”. The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera “common variety” were evaluated to test the anti-inflammatory and antinociceptive activities.

Materials and methods

Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50 mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50 mg/kg), and the references drugs morphine (5 mg/kg), acetilsalicilic acid (200 mg/kg), prometazine (30 mg/kg), and metisergide (5 mg/kg) were evaluated on models of analgesia and inflammation.

Results

CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5 mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin.

Conclusions

results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.