Maximal Electric Shock Research Articles

Empagliflozin modulates seizure activity and oxidative stress in rats with epilepsy

Drug-resistant epilepsy, a commonly devastating condition, affects more than 50 million people globally. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of neurological disorders, and a potential association between epilepsy and subsequent T2DM has emerged. Inhibiting sodium-glucose linked transporters (SGLTs), which are differentially expressed in the brain, has been shown to reduce epileptic episode activity. This study aimed to evaluate the anticonvulsive effect of empagliflozin in rats with seizures induced by maximal electric shock (MES) and pentylenetetrazol (PTZ). Generalized tonic‒clonic seizures were induced in the rats using an electroconvulsive meter, and pentylenetetrazol was injected to induce absence seizures. The duration of all the stages of seizure and Racine stage scoring (RSS) were performed. Malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) levels in the brain tissues were determined. Histopathological analysis of the brain tissues was carried out. A significant (p <0.01) decrease in the duration of tonic hind limb extension (THLE), a significant decrease in the levels of pro-oxidants such as MDA and NO, and an increase in the levels of antioxidants such as GSH were observed in the low dose 10 mg/kg and high dose 20 mg/kg empagliflozin groups compared to the disease control group. Histopathological analysis revealed a greater number of healthy neurons with few dark-stained cells in the treatment groups, suggesting the neuroprotective effect of empagliflozin. The present study showed that empagliflozin modulates epileptic activity. Empagliflozin has a potential role in the management of epilepsy in diabetic patients.

A preclinical study to determine the anti-epileptic effect of biotin on maximal electroshock (MES) and pentylenetetrazole (PTZ) models in albino rats.

Vitamin B7(biotin) is not synthesized in our body and is retrieved from some food products like eggs, liver, pork and leafy vegetables and as well as microbes of gut. Deficiency of biotin majorly leads to loss of hair, rashes over skin, lethargy and seizures. It is noted that biotin is an anti-oxidant and negates free radical effects. Biotin is also involved in carbon dioxide metabolism and it might alter seizure threshold. Studies also suggest its effect on lipid metabolism as well. So, the primary objective of this study was to assess the efficacy of biotin in maximal electric shock (MES) induced generalized tonic-clonic seizures (GTCS) and pentylenetetrazole (PTZ) induced absence seizures. The secondary objective is to study the effect of combined treatment of biotin and sodium valproate on seizures as well as plasma lipid profile in rats. In our study 30 albino Wistar rats each were used in MES and PTZ model respectively. 30 rats were divided equally into following groups: I- distilled water (negative control) II- distilled water (positive control) III- sodium valproate (300 mg/kg) IV- biotin (10 mg/kg/day) V- biotin (10 mg/kg)+sodium valproate (150 mg/kg). We observed that the tonic hind limb extension was significantly reduced in the treatment group in MES model. Nitric oxide levels were also seen raised in combination group in MES model and all the treated groups in PTZ model. Biotin treated group showed increased high-density lipoproteins and reduced low density lipoproteins and triglycerides. Biotin had an additive effect to sodium valproate in both the models of epilepsy in rats. Further, it was also able to counteract hyperlipidemia cause by sodium valproate.

The anticonvulsant effect of digoxin on basic models of primary generalized seizures does not depend on the route of administration

Improving the prevention and treatment of epilepsy is one of the urgent tasks. Based on the available data on the anticonvulsant activity of the cardiac glycoside digoxin, it is advisable to compare the anticonvulsant effect of the drug by different routes of administration in the experiment. Aim. To determine the impact of the route of administration on the anticonvulsant effect of the cardiac glycoside digoxin on basic models of primary generalized seizures induced by pentylenetetrazol and maximal electric shock. Materials and methods. Two basic models were used: the model of primary generalized convulsions induced in mice by pentylenetetrazol (80 mg/kg subcutaneously) and maximal electric shock (current strength – 50 mA, frequency – 50 Hz, 0.2 sec corneally). Digoxin was administered in the dose of 0.8 mg/kg (about 1/10 LD50) 30 min before modeling seizures in the stomach and subcutaneously. Standard parameters of convulsive syndrome severity and mortality were recorded. Results and discussion. In both seizure models, the anticonvulsant effect of digoxin was little dependent on the route of administration. In the pentylenetetrazole-induced model, with both routes of administration, lethality tended to decrease; when administered intragastrically, digoxin statistically significantly reduced the number of clonic-tonic seizures per 1 mouse, the number of animals with the most severe tonic seizures, and the duration of the convulsive period; when administered subcutaneously, it significantly increased the latent period of seizures and reduced the number of animals with tonic seizures. In the model of maximal electric shock, digoxin reduced seizure severity andlethality almost equally by both routes of administration (by 55 % with the intragastric administration and by 67.5 % with the subcutaneous administration). In both models, there were no statistically significant differences in the course of seizures in both routes of the digoxin administration. With subcutaneous administration, the anticonvulsant effect was somewhat more pronounced at the level of a weak tendency. Conclusions. The anticonvulsant effect of digoxin when administered intragastrically and subcutaneously in mice with models of pentylenetetrazole-induced seizures and maximal electric shock is practically independent of the routeof administration. Digoxin has a pronounced anticonvulsant effect on the model of electrically induced seizures, and a moderate effect on the model of pentylenetetrazole seizures.

Evaluation of Anticonvulsant Activity of Hydro Ethanolic Extract of Coccinia grandis in Mice

Background: Hydro ethanolic extract of Coccinia grandis leaves was assumed to have anticonvulsant activity. Objective: To evaluate the anticonvulsant activity of Coccinia grandis by using some animal models like maximal electric shock model, pentylenetetrazole induced seizures, Isoniazid induced seizures. Materials and Methods: Various equipment and apparatus were used in the present study. Hydroethanolic extract of Coccinia grandis was done by Soxhlet apparatus. Phytochemical investigation of the leaf extract of Coccinia grandis was performed. Anticonvulsant activity was determined by using different animal models like maximal electric shock model, pentylenetetrazole induced seizures, Isoniazid induced seizures. Results: Anticonvulsant activity was determined by using different animal models like Maximal electric shock model, pentylenetetrazole induced seizures & Isoniazid induced model. Percentage of protection, Duration of hind limb tonic extension (HLTE), Latency of onset of convulsions were taken as a indication of anticonvulsant activity. Phenytoin and Diazepam showed significant anticonvulsant activity. In the present study the test samples exhibited significant (P < 0.0001) anticonvulsant activity and antioxidant activity at a dose of 200,400mg/kg. It may due to the presence of alkaloids, Phenols, carbohydrates, glycosides, saponins and flavonoids terpenoids. Conclusion: In present study leaves of Coccinia grandis extract was collected and anticonvulsant activity was examined in a doses of 200mg/kg, 400mg/kg. The results clearly shown that the low dose 200mg/kg of plant extract shown appropriate anticonvulsant activity and the high dose 400mg/kg shown specific anticonvulsant activity when compared to control and standard groups.

HPLC and GC–MS–based metabolic profiles and in vivo anticonvulsant, sedative, and antinociceptive potentials of truffles Tirmania nivea and Tirmania pinoyi hydromethanolic extracts in mice

GC-MS and HPLC analyses of the hydromethanolic extracts of the truffles Tirmania nivea (TN) and Tirmania pinoyi (TP) revealed the presence of 18 metabolites and 11 polyphenols, respectively. In vivo, TP extract protected against subcutaneous pentylenetetrazole (scPTZ) and maximal electric shock (MES)-induced convulsions faster than TN extract. TP extract (100 and 300 mg/kg) showed 100% protection and longer duration than TN extract in the scPTZ test. Similarly, at 300 mg/kg, TP demonstrated a quicker start (75%) and longer duration of action (100%) than TN in MES test. In the scPTZ test, ED50 of TP demonstrated greater anticonvulsant efficacy than that of TN. In mice given TP and TN treatments, the brain GABA levels noticeably increased. TP (100 and 300 mg/kg) produced a notable sedative effect in open-field test, whereas TN (100 or 300 mg/kg) and TP (300 mg/kg) reduced sleep latency by 52%, 45%, and 79%, respectively. In writhing test, TN (100 or 300 mg/kg) significantly enhanced analgesic efficacy by 50 and 87%, respectively. Comparatively, in formalin test, TP and TN at a dosage of 300 mg/kg decreased the length of the licking by 34 and 59%, respectively. For the first time, this study explains the anticonvulsant, sedative, central, and peripheral analgesic activities of truffle extracts.

The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms

BackgroundEpilepsy is a neurodegenerative condition characterized by uncontrollable convulsions caused by a misalignment of the central nervous system's inhibitory and excitatory branches. Vateria indica is a medicinal herb with anti-inflammatory, anthelmintic, antiulcer, antitumor, and anticancer properties. ObjectivesTo investigate the antiepileptic activity of Vateria indica using maximal electrical shock (MES), pentylenetetrazole (PTZ), and isoniazid (INH) induced experimental animal models. MethodologyVateria indica bark was subjected to Soxhlet extraction using ethanol and quantitative and qualitative analysis was performed. The antiepileptic activity of Vateria indica bark extract (VIE) was investigated using different animal models in mice. GABA levels in the brain and antioxidant capacity in vitro were estimated. ResultsTreatment of mice with VIE significantly reversed the MES-induced convulsions, which was reflected by the decrease in the duration (sec) of all the phases of MES-induced convulsions, with an increment in the GABA levels. In the PTZ and INH models, pretreatment with VIE delayed the latency to clonic convulsions (p 0.001), reduced the intensity and duration of clonic convulsions, and reduced the mortality rate in the treatment groups in a dose-dependent manner. VIE intervention dose-dependently restored brain GABA levels. VIE also exhibited significant in-vitro antioxidant activity. ConclusionOverall, the findings imply that Vateria indica has substantial antiepileptic activities, mediated by positive GABAergic neurotransmission and antioxidant capabilities. To summarize, Vateria indica may provide adequate protection against epileptic seizures, suggesting that it could be used to treat petitmal and grandmal epilepsy. We plan to provide pure lead compounds derived from Vateria indica in the future in order to better understand the role it could play in the development of natural anticonvulsant drugs.

Investigation of chitosan, its depolymerized products, and nanoformulation as novel anticonvulsants

Objectives Chitosan is a natural biopolymer that possesses various biological activities. The aim of the current study was to evaluate the potentiality of chitosan and its enzymatically depolymerized products as anticonvulsants.Materials and methods In the current study, chitosan enzymatic depolymerization was carried out using Bacillus cereus chitosanase followed by fractionation of the produced chitooligosaccharides. Phase I anticonvulsant activity of chitosan as well as its enzymatically depolymerized products was evaluated using pentylenetetrazole-induced seizures, maximal electric shock, and neurotoxicity tests. In phase II, median effective dose, median toxic dose, and protective index were determined. In addition, γ-aminobutyric acid brain level and acute toxicity were evaluated.Results and conclusion The results indicated that the fraction with the lower degree of acetylation and longer chains of glucosamine (COSH) possessed rapid onset of action with the highest protection (75%) at 0.5 h and long-acting effect for 4 h. In addition, the median effective dose of COSH was 12.7-fold more potent than the reference ethosuximide, whereas in the maximal electric shock test, COSH showed lower potency than phenytoin. The median toxic dose was 1.4-fold and 7.9-fold higher than ethosuximide and phenytoin, respectively. The protective index was 18.1-fold and 3.98-fold higher than ethosuximide and phenytoin, respectively, with a significant increase in γ-aminobutyric acid neurotransmitter brain level. In an attempt to prolong the anticonvulsant effect of COSH, a nano-formulation was carried out in which the particle size was estimated as 188.7±0.26 nm. After that, an equivalent dose of a combined treatment of COSH and the nanoformula (each 15 mg/kg) was evaluated in which a prolonged effect was achieved up to 24 h.

Synthesis, Molecular Docking, and Biological Evaluation of Some Novel 2- (5-Substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole Derivatives as Anticonvulsant Agents.

Benzothiazole is an organosulfur heterocyclic compound that has a considerable place in drug discovery due to significant pharmacological actions. The main objective of the present study was to synthesize some novel 2-(5-substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant activity using in silico and in vivo methods. A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by suitable spectral techniques. The synthesized compounds were evaluated for anticonvulsant activity using in silico and in vivo methods. In silico molecular docking study was performed using Molegro Virtual Docker software to analyze binding modes of compounds with the internal ligand of PDB ID: 1OHY and 1OHV; and in vivo pharmacological activities were tested for both generalized tonic-clonic seizures and generalized absence (petit mal) seizures using Maximal Electrical Shock and PTZ-induced seizure models, respectively. Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3- benzothiazole (5a-5p) were successfully synthesized by finally refluxing 1, 3-benzothiazole-2-carboxyhydrazide with different aromatic acids in phosphoryl chloride. Docking results showed that compounds 5c, 5j, and 5m were found to have the highest number of H-bond interactions; i.e. 4, 4, and 7 respectively with target proteins 1OHY and 6, 3, and 4 respectively with target protein 1OHV, whereas phenytoin showed only two H-bonding with both proteins. In the Maximal electroshock seizure method, the synthesized compounds 5h, 5k and 5o demonstrated potent anticonvulsant activity against the tonic seizure with a significant decrease in tonic hind leg extension period with a mean duration of 7.9, 7.4, and 7.0 sec respectively, as compared to the other synthesized compounds. In contrast, in the PTZ-induced seizure model, compounds 5c, 5h, and 5m showed protection against clonic convulsion with significant elevation in the onset time of clonic convulsion at 311.2, 308.0, and 333.11 sec, respectively. Thus, from the results, it can be concluded that compound 5h, a benzothiazole derivative endowed with an oxadiazole ring, can be developed as a potential anticonvulsant agent.

Phenytoin Attenuates Seizure Severity and Hippocampal Derangement than Levetiracetam or Phenytoin-Levetiracetam Adjunctive Treatment in Electrically-Convulsed Mice

This study evaluated the anticonvulsant and neuroprotective efficacy of individual or adjuvant treatment of two different antiepileptic-drugs (AEDs) phenytoin (PHT) and levetiracetam (LEV) against maximal electric shock in mice model. Twenty-five male Albino mice, randomized into five groups (n=5) received treatment as follows: groups 1 and 2 received intraperitoneal (i.p) administration of normal saline (0.1 ml), while groups 3-5 received a therapeutic dose of PHT (50 mg/kg BW) or LEV (50 mg/kg/day BW), or combination of PHT (25 mg/kg) and LEV (25 mg/kg) at sub-therapeutic doses. Thirty minutes later, the mice in groups 2-5 were challenged with maximal electroshock, while various indices of convulsion were determined, while the histomorphological profile of the hippocampus investigated. Data were analyzed using descriptive and inferential statistics with the help of graph pad prism software. The results were presented as mean ± SEM in the graph or table. The level of significance was taken at p<0.05. There was a decrease (p = 0.0001) in the duration of tonic flexion, tonic limb extension, clonic convulsion, stupor, and righting reflex in all the drug-treated groups compared with positive control. Also, the duration of clonic convulsion significantly decreased in the PHT (p = 0.0003) and PHT + LEV treated mice compared with LEV treated. There was significant (p = 0.0001) damage in the neuronal hippocampal tissue of the untreated mice. Funding Information: The authors declared that this research was self-sponsored. Declaration of Interests: The authors declared that this research was conducted in the absence of any commercial or financial relationships that could interpret as potential conflict of interest. Ethics Approval Statement: The experimental protocol was approved by the Health Research Ethics Committee, Institute of Public Health, Obafemi Awolowo University, Ile –Ife which also comply with the ARRIVE guidelines and should be carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.

Evaluation of the anticonvulsant activity of the phosphodiesterase III inhibitor cilostazol in the animal model of epilepsy

The present study is objected to evaluate the anticonvulsant activity of the phosphodiesterase III inhibitor cilostazol in the animal model of epilepsy. Conventional anti-epileptic rodent models like Maximal Electric Shock (MES)- induced convulsions and Pentylenetetrazol (PTZ) induced convulsions were used. The animals were randomly divided into six groups, with six rats in every group. Here anti-epileptic activity of cilostazol with two different doses (10 mg/kg i.p and 20 mg/kg i.p) was compared with standard drug and standard drug + Cilostazol two different doses (10 mg/kg i.p and 20 mg/kg i.p). Cilostazol (20 mg/kg i.p) exhibited an anticonvulsant effect in MES-induced and PTZ induced convulsion models over the Control group and cilostazol (10 mg/kg i.p). Standard drugs were shown superiority in seizure suppression activity than cilostazol (20 mg/kg i.p). The time duration of onset of clonic convulsion and period of clonic convulsions in PTZ induced convulsion were increased and decreased respectively when compared to Standard drug + cilostazol both doses and standard drug alone. Phenytoin abolished convulsions induced by MES- convulsion model. So the present study established that cilostazol has low anticonvulsant efficacy in comparison with conventional drugs (Phenytoin and Sodium Valproate). The potentiating effect of cilostazol with standard drugs was also demonstrated.

New positive allosteric modulator of AMPA-receptors: in vitro and in vivo studies

A new derivative of 3,7-diazabicyclo[3.3.1]nonane was studied in electrophysiological experiments, which showed high activity as a positive allosteric modulator of AMPA receptors of the CNS. In doses of 0.01 mg/kg this compound significantly improved the memory of experimental animals disturbed by maximal electric shock. The results indicate that this compound is a promising candidate for preclinical and clinical studies as a treatment for a number of psycho-neurological diseases.

New Positive Allosteric Modulator of AMPA Receptors: in vitro and in vivo Studies.

A new derivative of 3,7-diazabicyclo[3.3.1]nonane, which showed a high activity as a positive allosteric modulator of AMPA receptors of the CNS, was studied in electrophysiological experiments. At doses of 0.01 mg/kg, this compound significantly improved the memory of experimental animals disturbed by maximal electric shock. The results indicate that this compound is a promising candidate for preclinical trials and clinical studies as a drug for treatment of a number of psychoneurological diseases.

Anticonvulsant and GABAnergic Activity of Nigella sativa oil in Mice

Several experimental studies have described neuroprotective and antioxidant activity of plant extracts and its oil as Nigella sativa. The existing study was conducted to investigate the anticonvulsant activity of Nigella sativa oil. Fifty five male albino mice were used through three experiments; each experiment was taken 1 week. The experiments were pentylenetetrazole induced convulsion, maximal electric shock induced convulsion and neurotoxicity tests. Mice were treated with Nigella sativa oil 10 ml/kg; using sodium valproate (100 mg/kg) and phenytoin sodium (25 mg/kg) orally as standard drugs. In pentylenetetrazole induced convulsion, onset of seizure and generalized seizures were measured, beside the gamma aminobutyric acid and antioxidant enzymes levels assessments. In maximal electric shock, mice were observed for hind limb tonic convulsion. Nigella sativa oil significantly delayed seizure onset after pentylenetetrazole induced convulsion but had no effect on electric shock induced convulsion. Nigella sativa showed a good antioxidant activity and increased gamma amino butyric acid level in brain and had neuroprotective effects.

Anticonvulsant Activity of Hydroalcoholic Phoenix dactylifera Fruit Extract and Pimpinella anisum Oil in Mice

Epilepsy is a group of long-term neurological disorders characterized by epileptic seizures. The present study sought to investigate the anticonvulsant and neuroprotective Activity of Hydroalcoholic Phoenix dactylifera fruit extract (HAPD) and Pimpinella Anisum Oil (PAO) against Pentylenetetrazole (PTZ) and Maximal Electric Shock (MES) induced a seizure in mice. Mice groups were treated with HAPD1000 mg/kg, PAO 4 ml/kg. The onset of a seizure and generalized seizure were measured, followed by Gamma-Aminobutyric Acid (GABA) and antioxidant enzymes assessments. The potential of these substances to induce any neurological toxicity was also evaluated by using rotarod, forced swim test and horizontal screen test. The current study demonstrates that HAPD and PAO delay onset of the seizure and generalized seizure, also elevated GABA and antioxidant enzymes level and haven’t any neurological toxicity. The current study suggests that hydroalcoholic Phoenix dactylifera extract and Pimpinella anisum oil have anticonvulsant, neuroprotective and antioxidant activity and can increase brain GABA level.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

STUDY OF THE ANTICONVULSANT ACTIVITY OF ETHANOLIC EXTRACT OF ROOT OF ACORUS CALAMUS IN ALBINO RATS

Objective: Root of Acorus calamus has been traditionally used as an anticonvulsant. The aim of the study is to assess the anticonvulsant activity of ethanolic extract of A. calamus (EEAC) by maximal electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models on albino (Wistar strain) rats.Methods: Albino rats were taken and divided into five groups, each consisting of five rats both for MES and PTZ model. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin in MES model/diazepam in PTZ model), and three groups for the test drug (EEAC in the doses of 100, 200, and 400 mg/kg). In MES model, maximal electrical shock of 150 mA was passed for 0.2 s through earlobe electrodes after 30 min of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. In PTZ model, PTZ was injected 30 min after giving the drugs and normal saline, and onset of action and severity of convulsions were noted. Data were statistically analyzed by one-way analysis of variance followed by multiple Dunnett’s test.Results: EEAC dose dependently reduced the duration of tonic hind limb extension in MES model, and there was increase in latency and occurrence of convulsions in PTZ model.Conclusion: EEAC has anticonvulsant activity.

Derivatives of a new heterocyclic system - pyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines: synthesis, docking analysis and neurotropic activity.

8-Hydrazino derivatives of pyrano[3,4-c]pyridines and derivatives of the new heterocyclic system 3-thioxopyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines on the basis of methanesulfonates of pyrano[3,4-c]pyridinium were synthesized by optimization of a previously used method. Derivatives of alkylsulfonyl pyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines were also synthesized. All compounds were evaluated for their neurotropic activity. Among all the compounds tested for anticonvulsant activity by pentylenetetrazole and maximal electric shock seizure (MES) tests, six compounds (5a, 5b, 5e, 5g, 5j, and 5p) appeared to be active. These compounds were also evaluated for their anxiolytic as well as antidepressant activities using "open field", "elevated plus maze" (EPM), and "forced swimming" tests, respectively. It should be mentioned that compounds tested by the "rotating rod" method did not affect neuromuscular coordination. The most active compound appeared to be 5g in all tests. Docking studies of the most active compounds were performed on the GABAA receptor, SERT and 5-HT1A receptor.

Madhuca longifolia water extract revealed protective effect against MES, PTZ and Li-pilocarpine induced epilepsy

Objective: Present study was designed to screen the antiepileptic property of aqueous extract of Madhucalongifolia (AqML) in laboratory animals. Materials and methods: Rat and mice were divided in different groups. Antiepileptic activity was tested by using maximal electric shock (MES), Pentylenetertrazole (PTZ) and lithium pilocarpine (Li-Pilocarpine) models. Treatment group of animals were received AqML at 100, 200 and 400 mg/kg p.o. for 7 days. At the end of treatment period, different parameters related of antiepileptic action were observed. Result: Preliminary phytochemical investigation revealed the presence of carbohydrate, protein, amino acid and alkaloids. Animals treatment with AqML showed significant (p&lt;0.05) antiepileptic activity in MES, PTZ and li-pilocarpine screening models. In all the screening models AqML showed dose dependant prevention in seizure was observed and of them dose 400mg/kg p.o. was found to be very significant (p&lt;0.05) antiepileptic effect. Conclusion: The result revealed that AqML at 400 mg/kg p.o. possesses antiepileptic activity in MES, PTZ and Li-pilocarpine models.

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK-3β signaling pathway.

Previous reports on the pharmacological actions of geniposide have indicated that it has anti-asthmatic, anti-inflammatory and analgesic effects in the liver and gallbladder, and therapeutic effects in neurological, cardiovascular and cerebrovascular diseases. The results of the current study demonstrate that geniposide attenuates epilepsy in a mouse model through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A mouse model of epilepsy was induced by maximal electric shock (50 mA, 50 Hz, 1 sec). Epilepsy mice were intragastrically administered with 0, 5, 10 or 20 mg/kg geniposide. Geniposide significantly reduced the incidence and significantly increased the latency of clonic seizures in epileptic mice compared with non-treated epileptic mice (both P<0.01). Geniposide treatment significantly inhibited cyclooxygenase-2 mRNA expression in epilepsy mice (P<0.01). Furthermore, geniposide significantly suppressed the protein expression of activator protein 1, increased the activation of Akt and increased the protein expression of GSK-3β and PI3K in epilepsy mice (all P<0.01). These results suggest that geniposide attenuates epilepsy in mice through the PI3K/Akt/GSK-3β signaling pathway.

Pharmacological evidence for the anticonvulsant activity of Tylophora indica in experimental animal models

Background: Epilepsy is a common neurological disorder. The antiepileptic drugs currently used are unable to manage seizures effectively and are associated with numerous adverse drug effects. Hence, there is a necessity of a newer anticonvulsant drug with high therapeutic index profile. The objective of this pre-clinical research was to investigate the role of Tylophora indica on Maximal electric shock [MES] and Pentylene tetrazole [PTZ] provoked convulsions in Wistar albino rats.Methods: 36 Wistar albino rats were used for this study, after obtaining ethical clearance. The ethanolic extract of the leaves of Tylophora indica [TIEE] (100 mg/kg, p.o) was used to screen the anticonvulsant effect on MES and PTZ provoked convulsions in Wistar albino rats. In MES seizures, inhibition of the tonic hind limb extension and in PTZ seizures, extent of convulsions was noted.Results: TIEE (100 mg/kg, p.o) significantly (p&lt;0.001) blocked the hind limb extension due to MES. The same dose also significantly (p&lt;0.001) lessened the extent of convulsions induced by PTZ.Conclusions: The data suggests that the ethanolic extract of Tylophora indica leaves produce its anticonvulsant effect via different mechanisms since it prevented the hind limb extension induced by MES and decreased the duration of convulsions produced by PTZ.