Phytochemical and Anticonvulsant Activity of the Ethanol Root Bark Extract of <i>Mimosa pigra L.</i> (Fabaceae) in Laboratory Animals

Effect of ACEA—a selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model

Background: Epileptic seizures affect approximately 10% of the global population and are associated with morbidity, mortality, and economic burden. Despite the availability of antiepileptic drugs, a lot of patients remain resistant to current treatments. Neuroinflammation and oxidative stress are important contributors to seizure pathophysiology. Bavachinin is a flavonoid derived from Psoralea corylifolia, which has been demonstrated to have antioxidant and anti-inflammatory characteristics. Objectives: This study aimed to evaluate the anticonvulsant potential of bavachinin in a pentylenetetrazole (PTZ)-induced seizure model in mice, emphasizing its antioxidant and anti-inflammatory effects. Methods: Twenty-eight male mice were randomly divided into four groups: control, bavachinin alone (200 mg/kg, PO), PTZ alone (400 mg/kg, IP), and bavachinin + PTZ. Seizure latency was recorded. Moreover, hippocampal tissues were examined for malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tumor necrosis factor-alpha (TNF-α) concentration using biochemical and ELISA techniques. Results: Bavachinin significantly delayed the onset of PTZ-induced seizures and prevented progression to the most severe stage (stage 5). PTZ-induced seizures elevated MDA and TNF-α levels while reducing SOD activity in the hippocampus. Bavachinin pretreatment markedly reduced MDA and TNF-α levels and restored SOD activity, indicating potent antioxidative and anti-inflammatory effects. Novelty of the Study: This study addresses the gap in epilepsy treatment regarding the lack of a natural compound with therapeutic potential. This study evaluates the anticonvulsant, antioxidant, and anti-inflammatory effects of bavachinin in a PTZ-induced seizure model in mice. By demonstrating that bavachinin not only delays seizure onset but also significantly modulates oxidative stress markers (MDA, SOD) and pro-inflammatory cytokines (TNF-α), this work introduces a novel, plant-derived compound with anticonvulsant, antioxidant, and anti-inflammatory properties. Conclusions: Bavachinin represents anticonvulsant, antioxidant, and anti-inflammatory activities in PTZ-induced seizures in mice. It is advised that its mechanics and clinical use be further investigated. Keywords: Bavachinin, seizure, pentylenetetrazol (PTZ), oxidative stress, neuroinflammation, malondialdehyde (MDA).

Aims: The aim of this research is to investigate the preliminary phytochemical properties, acute oral toxicity and anticonvulsant activity of the seed extract of Brassica juncea (B. juncea). Study Design: Qualitative analysis of for phytochemicals was performed. Experimental mouse model was contributed for toxicity test and anticonvulsant activity of pentylenetetrazole (PTZ) induced seizure. Place and Duration of Study: Applied Biochemistry Laboratory, Department of Applied Biochemistry, School of Biotechnology, International University, Vietnam National University, Ho Chi Minh, between June 2014 and December 21014. Methodology: Phytochemicals from the methanol seed extract were screened by standard methods. Acute oral toxicity study was conducted as per Organization for Economic Co-operation and Development (OECD) 425 guidelines while anticonvulsant activity was assessed against PTZinduced seizure in mice. The effect of the extract at dose levels of 200, 300, 400 and 500 mg/kg body weight was evaluated in an experimental mice model, using diazepam as positive control (5 Original Research Article Duy and Trang; EJMP, 14(1): 1-9, 2016; Article no.EJMP.25525 2 mg/kg, p.o). At the end of the observation period, the animals were sacrificed and their brains were removed for histopathological examination. Results: The phytochemical study showed the presence of alkaloids, flavonoids, saponins, tannins, terpenoids, and phenolic compounds in the seeds of B. juncea. The Acute oral toxicity study indicated that the extract was safe and non-toxic to mice up to 5000 mg/kg body weight. The extract significantly delayed the latency of convulsion (p ˂ 0.05) induced by PTZ at the dose of 500 mg/kg p.o. The extract also reduced the frequency of convulsion and provided up to 100% protection (500 mg/kg p.o) against death. Conclusion: The data suggest that the methanol seed extract of B. juncea is safe and possesses anticonvulsant activity in PTZ-induced seizure in mice.

The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice

Context: The adventitious roots of Ficus religiosa L. (Moraceae) have been extensively used in traditional medicine for treatment of several disorders, including epilepsy.Objective: To investigate the possible anticonvulsant effect of the adventitious roots of Ficus religiosa, and to find the biologically active fraction, to substantiate its traditional use in epilepsy.Methods: The hydroethanolic extract of adventitious roots (5, 10, and 20 mg/kg; i.p.) of Ficus religiosa and its different fractions (hexane, chloroform, ethyl acetate, butanol, aqueous, saponins-rich, and saponins-lacking) at a dose equivalent to 20 mg/kg of the extract were administered 30 min prior to the induction of maximal electroshock (MES) and pentylenetetrazol (PTZ) convulsions. Duration of tonic hind-limb extension (THLE) and latency to clonic convulsions were noted in MES and PTZ tests, respectively. Neurotoxicity was assessed using rotarod test.Results: Treatment with the root extract (5, 10, and 20 mg/kg; i.p.), butanolic (6 mg/kg; i.p.) and saponins-rich fractions (3.4 mg/kg; i.p.) significantly (p < 0.05) decreased the duration of THLE in MES test, as compared to control. The same treatment also significantly (p < 0.05) increased the latency to PTZ-induced clonic convulsions in comparison to control. The other fractions were found to be ineffective. The root extract and its active fractions at their effective doses showed no neurotoxic effects.Conclusion: The present study concluded that the hydroethanolic extract of adventitious roots of Ficus religiosa has anticonvulsant activity. Retention of anticonvulsant effect in the saponins-rich fraction-treated animals indicated the role of saponins for the activity.

Cusonea aborea is used in the treatment of both infectious and non-infectious diseases. The objective of this study was to investigate the anticonvulsant activity of methanol leaf extract of the plant in experimental animals. Phytochemical screening and acute toxicity studies were conducted. The anticonvulsant activity of the extract at doses of 75, 150, 300 and 600 mg/kg was evaluated in chicks (using maximal electroshock test) and mice (using pentylenetetrazole, 4-aminopyridine, strychnine, picrotoxin and isoniazid-induced) seizures models. Phytochemical screening revealed the presence of alkaloids, flavonoids, cardiac glycosides, saponins, tannins, streroids, anthraquinones and triterpines. Intraperitoneal median lethal dose was estimated to be 2000 and 3800 mg/kg in mice and chicks respectively. The extract offered 40 % protection at 150, 300 and 600 mg/kg against maximal electroshock test. Protection of 50 and 33.33 % was offered at 75 and 150 mg/kg respectively against pentylenetetrazole-induced seizures. At 300 mg/kg, the extract confered 66.67 % protection and significantly (p&lt;0.05) increased the onet of seizures in 4-aminopyridine test. Protection of 83.33 % and significant increase (p&lt;0.05) in the onset of seizure was seen at 300 mg/kg in strychnine-induced seizures. There was significant (p&lt;0.05) increase in the onset of seizures at 300 mg/kg against picritoxin-induced seizures. No protection was offered by the extract against isoniazid-induced seizures at all of the tested doses. The findings revealed that the methanol leaf extract of Cusonea aborea possesses anticonvulsant activity and this may provide scientific basis for the use of the plant in the treatment of epilepsy.

Current understanding of the mechanism of action of the antiepileptic drug lacosamide

Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg

Background: Epilepsy is one of the most common, serious neurological conditions, affecting more than 50 million people worldwide. This disorder is characterized by the occurrence of spontaneous and recurrent seizures due to the abnormal, excessive, and synchronous electrical firing of neuronal networks Aim: The objective of the present study was to evaluate Pistacia integerrima (PI) gall extracts in acute models of epilepsy for their anticonvulsant activity. Materials and Methods: Extraction of galls of PI using a Soxhlet apparatus was carried out to yield petroleum ether and methanolic extracts. Both the extracts were screened in pentylenetetrazole (PTZ)-induced seizures in the zebrafish model. The active extract was further evaluated in the PTZ-induced seizures in mice. Both extracts were further screened in the maximal electroshock (MES) model in rats. Results: The petroleum ether extract of Pistacia integerrima (PEPI) exhibited dose-dependent delay at 50mg/kg, 100mg/kg, and 200 mg/kg in the onset of different seizure parameters in PTZ-induced seizures in the zebrafish model that was further confirmed in mice at 50 mg/kg and 100 mg/kg. In addition, the extract exhibited delay in the duration of hind limb extension (HLE) as well as protected from it at 50 mg/kg, 100mg/kg, and 150 mg/kg in the MES model in rats. The metabolic extract of Pistacia integerrima (MEPI) was unable to protect from seizures in both preliminary screening (PTZ and MES) models. Conclusion: The results showed that PEPI demonstrated potential anticonvulsant activity in zebrafish and rodent models of epilepsy. This may be attributed to the presence of essential oil and its phytoconstituents, indicating its role in suppressing generalized absence and tonic-clonic seizures.

An antagonist of calcium permeable AMPA receptors, IEM1460: Anticonvulsant action in immature rats?

Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZ-induced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 μM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 μM).

Introduction: The use of Asparagus adscendens (family:Liliaceae) root powder has been reported traditionally for the treatment of epilepsy. But, it is yet to be validated pharmacologically. Therefore, the present study was undertaken to explore the anticonvulsant effect of the roots in the experimental animal models of convulsions. Materials and Methods: The anticonvulsant effect of hydroethanolic root extract of A. adscendens (AAE) was studied at 25, 50, and 100 mg/kg; intraperitoneally (i.p.) in maximal electroshock (MES), and at 25, 50, 100, and 200 mg/kg; i.p. doses in pentylenetetrazol (PTZ) test in mice. The duration of tonic hind limb extension (s) and latency to tonic-clonic convulsions (min) was noted in MES and PTZ tests, respectively. Phenytoin (25 mg/kg; i.p.) and diazepam (5 mg/kg; i.p.) served as reference standards in MES and PTZ tests, respectively. Percentage mortality was also noted. Results: The AAE treatment did not show any protective effect with regard to induction and duration of tonic hind limb extensor in MES test and latency to tonic-clonic convulsions in PTZ test, as compared to their respective controls. Conclusions: The results obtained from the experiments indicate that the AAE lacks anticonvulsant activity in MES- and PTZ-induced convulsion tests.

The present study was conducted to investigate the possible interaction between low doses of nicotine and pentylenetetrazole (PTZ) in vivo and also to evaluate the influence of nicotine on the antiseizure efficacy of topiramate and sodium valproate in the PTZ-induced seizure model in mice. Graded dose-response study with nicotine showed the CD50 value for nicotine at 6.76 mg/kg. i.p. Subtheshold dose of nicotine (4 mg/kg, i.p.) pretreatment significantly decreased the CD50 value for PTZ from 47.86 mg/kg, i.p. (of PTZ per se) to 31.62 mg/kg, i.p. Sodium valproate but not topiramate, significantly inhibited PTZ-induced seizures in mice with an ED50 value of 177.83 mg/kg, i.p. Nonconvulsive dose of nicotine (1 mg/kg, i.p.) significantly antagonized the protective efficacy of sodium valproate against PTZ-induced seizures and increased the ED50 value to 338.84 mg/kg, i.p. PTZ-induced seizures significantly increased the mouse brain levels of MDA and reduced the level of GSH while sodium valproate reversed such changes. Nicotine pretreatment reversed the anti-lipid peroxidative action of sodium valproate in the PTZ-induced seizure model in mice. The study highlighted the convulsant as well as proconvulsant role of nicotine and established dose discrimination for nicotine as a proconvulsant agent and an anti-antiseizure agent. The study bears significant clinical relevance particularly amongst epileptic smokers who may show failure of efficacy of antiepileptic agents and present with breakthrough seizure attacks on exposure to nicotine.

Repetitive transcranial magnetic stimulations of the rat. Effect of acute and chronic stimulations on pentylenetetrazole-induced clonic seizures.