Anticonvulsant activity of methanolic extract of Withania cogulans in mice

Mental and neurological diseases including depression, Parkinson’s disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world’s disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity.

ANTICONVULSANT ACTIVITY OF PORTULACA OLERACEA LINN. AND EUPATORIUM BRIMANICUM DC IN MES INDUCED SEIZURE: A COMPARATIVE STUDY

Objective: The study was aimed to evaluate and compare the anticonvulsant activity of aqueous leave extract of Portulaca oleracea Linn. and Eupatorium brimanicum DC in MES model in albino mice. Methods: Aqueous Extracts were prepared by the soxhlet extraction method. MES model was chosen to evaluate anticonvulsant activity. 36 albino mice were selected and divided into 6 groups for this model. Group I received 2% gum acacia 1 ml/100 g orally. Group II received phenytoin-20 mg/kg orally. Group III and IV received 200 and 400 mg/kg of Portulaca oleracea Linn. Respectively. Group V and VI received 200 and 400 mg/kg of Eupatorium brimanicum DC respectively. Results: The extracts didn’t show any toxicity and significantly reduced hind limb tonic extension (HLTE) duration in MES model (50 mA, 0.2 sec) at higher doses. Conclusion: The results suggest Portulaca oleracea Linn. and Eupatorium brimanicum DC extract possess anticonvulsant activity and justify their use in folk medicine.

EVALUATION OF ANTI-SEIZURE ACTIVITY OF SIDA RHOMBIFOLIAALONE AND IN COMBINATION WITH ANTI-SEIZURE DRUGS IN SWISS ALBINO MICE

Background-Anti-seizure activity of Sida Rhombifolia in low (300mg/kg) and high doses(600mg/kg) and its combination with Phenytoin(50mg/kg) and Sodium valproate(300mg/kg) were studied in chronic model (14 days) of Maximal Electroshock Seizure (MES) and Pentylenetetrazole (PTZ) induced seizure respectively. Methods- Anti-seizure activity of Sida Rhombifolia on generalized tonic-clonic seizure and absence seizure was evaluated using standard maximal electroshock seizure method and pentylenetetrazole test. Results- In MES induced seizures Sida Rhombifolia in high dose prevented both tonic extension and tonic flexion. In PTZ induced seizures Sida Rhombifolia in high dose significantly (p<0.001) increase the latency of onset of seizures and both high and low dose Sida Rhombifolia significantly decrease the duration of seizure (p<0.01) as compared to vehicle control, however, there was no significant effect on onset of 1st myoclonic jerk (p>0.05). The addition of Sida Rhombifolia to the sub- therapeutic dose of sodium valproate and phenytoin showed a synergistic effect. Conclusion- Inhibition of seizure by Sida Rhombifolia could be due to the presence of flavonoids that acts as a partial positive allosteric modulator at GABAA (γ-aminobutyric acid) receptors, penetrates the blood-brain barrier and possess the anti-convulsant activity and also because of its antioxidant property. Sida Rhombifolia can be effective in generalized tonic-clonic seizures alone and as add on with sodium valproate for absence seizures.

Anti-convulsant Action and Attenuation of Oxidative Stress by Citrus limon Peels Extractsin PTZ and MES Induced Convulsion in Albino Rats

Background: Citrus limon is a small evergreen plant belongs to family Rutaceae. Species are extensively cultivated throughout the world because of their multiple health benefits for humans and their applications in pharmaceutical and food industries. Various studies were conducted using its plant parts(fruits, flowers, peels, leaves, blossoms)but the studies on peel extracts are very limited. However,the anti convulsant activity of peels has not been studied yet. Objective: The main goal of this study is to appraise the anti convulsant effect striked by antioxidant property of Hydroalco-holicextracts of Citrus limon (HAECL) peels in various animal models. Methods: The anticonvulsant and in-vivo antioxidant activity of HAECL peels was carried outby Maximal electric shock(MES)model, pentylenetetrazole (PTZ)induced clonic convulsion model and PTZ induced kindling test. The extract was administered to test groups at doses of 200,400 and 600 mg/kg., orallyin PTZ and MES methods. The highest dose of ex-tract was given to the test grouped animals in case of kindling test. After completion of the time period of kindling the brains of all grouped animals were isolated and subjected to analyseoxidative stress parameters such asmalondehyde (MDA), Superoxide dismutase (SOD), Catalase(CAT) and glutathione (GSH) biochemically to investigate the antioxidant profile of the plant. Results: HAECL peels at doses of 400 and 600 mg/kg significantly (p<0.01) delayed the onset, decreased the duration of myoclonic spasmin PTZ induced seizure model and also significantly (p<0.01) decreased the duration of hind limb tonic extension (HLTE) as well as significantly (p<0.05)increased the postictalde pression (PID) in MES model compared to control.In PTZ-induced kindling model,the malondialdehyde (MDA)level was elevated in preference with diminished level of SOD, CAT, GSH compared to control group but pre treatment with HAECL at highest dose reduced the MDAlevelandre-finedSOD, CAT and GSH status effectively. Conclusion: From the above inquisition,it was concluded that HAECL is able to produce effective anti convulsant activity and also attenuate oxidative stress inducedduring seizure.

Study of the dynamics of anticonvulsant and anxiolytic action after oral administration of tin (II) chloride

This article is devoted to the study of anticonvulsant and anxiolytic activity of tin (II) chloride by oral administration. The anxiolytic effect was established in models of the Open Field and Black-and-White Camera tests; the anticonvulsant activity of SnCl (II) was evaluated in model of acute generalized seizures with the determination of pentylenetetrazole (PTZ) minimum effective doses inducing clonic-tonic convulsions and tonic extension in test animals. Statistical indicators were calculated using the Microsoft Excel software package using the arithmetic mean value (M) and the mean deviation mean value (m). The obtained data show that tin (II) chloride is a promising compound for the prevention of anxiety states, as well as disorders containing the convulsive component. Three hours after the start of the experiment, the minimum doses of pentylenetetrazole for inducing clonic-tonic convulsions and tonic extension, exceeded the control group data by an average of 75%. A decrease in motor activity by half compared with the control in the open field test during the 5 hours of the experiment indicates the sedative effect of tin (II) chloride. Tin (II) chloride is a promising compound for the relief of convulsive states and correction of depressive disorders. Thus, it is of interest to further study the spectrum of its pharmacological activity in order the use it in medicine.

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice

Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]

Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana Leaf in Mice

Aim: The study was carried out to determine the anticonvulsant potential of dichloromethane leaf extract of Aspilia africana. Study Design: Three seizure models namely: Pentylenetetrazole (PTZ), strychnine (STC) and maximal electroshock (MES) were used, motor coordination behavior of the animals were also assessed. Place and Duration of Study: The study was carried out between the months of October and November, 2017 at Pharmacology laboratory, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria. Methodology: The powdered leaves of A. africana (2000 g) were extracted with 10 liters of 100% dichloromethane. Doses of 25, 50, 100 and 200 mg/kg were administered to the test animals. Results: The chemical models, STC & PTZ showed 50% & 100% survival respectively. The delayed onset of seizure suggested anti-seizure potential of dichloromethane extract of A. Africana leaf with the maximal latency period of seizure recorded in the 25 mg/kg dose within the following chemical models, this was significant, P = .05 compared to the normal control. The MES method showed that at doses of 25 & 50, 100 mg/kg, the animals were 66.7% & 50% free of hind limb tonic extension (HLTE). Furthermore, there was reduced motor coordination potential at 25 mg/kg by 68.5%, which was significant at the level of, P = .05, compared to healthy control. Conclusion: From the preceding, it can be seen that the dichloromethane leaf extract of A. Africana has antiseizure potential.

Evaluation of anticonvulsant activity of ethanolic extract of Gomphrena serrata by using Swiss albino mice

Epilepsy is characterised by abnormal behaviour which is leading to tonic flexon, tonic extension, clonus and stupor. Many novel therapeutic regimens were used to treat these disorders through different ways including altering neurotransmission, but so far there is no specific treatment approach which is satisfactory to the patients in terms of complete cure. Our approach is to make understand the herbal medicines usage towards epilepsy. The ethanolic plant extract of Gomphrena Serrata at 400mg/kg, 600mg/kg and 800mg/kg were given to albino mice which were treated with maximum electric shock of 30mA current and pentelene tetrazolium in two different techniques. The results with these extract doses showed significant results which indicated decrease in clonic extension and stupor. Whereas there is no decrease in the tonic flexon observed with all doses. All these results were compared with the standard drug Phenytoin at 25mg/kg I.P. However, the ethanolic plant extract of Gomphrena Serrata at 600mg/kg showed marked increase in the therapeutic activity which is equivalent to Phenytoin and can be compared. Apart from these the ethanolic plant extract of Gomphrena Serrata at 400mg/kg, 600mg/kg and 800mg/kg showed significant decrease in the recovery times when compared to control group

Neuropharmacological Profile of Fractions of Actaea acuminata H. Hara Roots

The methanol extract of Actaea acuminata roots have beenpreviously reported to exhibit significant antianxiety, anticonvulsant andantidepressant activities. In present study fractionation of crude bioactivemethanol extract was carried out using different solvents employing standardprocedure. Various fractions were evaluated for antianxiety, anticonvulsantand antidepressant activities using elevated plus maze model (EPM), maximalelectroshock-induced convulsions model (MES) and forced / despair swim test(FST) respectively. Successive partitioning of bioactive methanol extract wasdone with ethyl acetate and 1-butanol. The ethyl acetate fraction (EAF; 100mg/kg), 1-butanol fraction (BF; 25 mg/kg) and remaining methanol extract(RME; 70 mg/kg) were subjected to neuropharmacological activities. TheEAF significantly enhanced entries and average time spent in open arms;significantly decreased duration of MES-induced tonic extension phase andsignificantly decreased duration of immobility time of rats in comparisonto control. BF and RME did not exhibit any neuropharmacological activity.Qualitative chemical tests confirmed presence of alkaloids and polyphenolsin EAF. It is finally concluded that alkaloids and/or polyphenols are bioactiveconstituents of A. acuminata which are responsible for neuropharmacologicalactivities.