Without doubt, natural products have been, and still are, the cornerstone of the health care armamentarium. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research.
This work progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with pharmacological activities. In the present study we investigated the efficacy of methanol extract and its semi-purified fractions (F2, F3) from Spongia officinalis for their in vivo anti-inflammatory activity using the carrageenan-induced paw edema in rats and their in vitro antiproliferative effects by their potential cytotoxic activity using the MTT colorimetric method and clonogenic inhibition against three human cancer cell lines (A549, lung cell carcinoma, HCT15, colon cell carcinoma and MCF7, breast adenocarcinoma).
The fractions F2 and F3 showed interesting anti-inflammatory and antiproliferative activities in a dose dependent manner.
The present study indicates that the methanolic extrac and its fractions from Spongia officinalis are a significant source of compounds with the antiproliferative and anti-inflammatory activities, and this may be useful for developing potential chemopreventive substances.
Spongia officinalis; Anti-inflammatory activity; Antiproliferative activity
The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.
To study the anticonvulsant activity and neurotoxicity of ethanolic extract and ethyl acetate fraction of the rhizome of Smilax china (EESC and EAF, respectively) in mice.
Materials and Methods:
The anticonvulsant activities of EESC and EAF were studied against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice and neurotoxicity was determined using rotarod test.
The duration of hindleg extension in MES test was reduced significantly (P < 0.001) by EESC at a dose level of 400 mg/kg and EAF at both higher dose levels (200 and 400 mg/kg). In PTZ model, the seizure latency was prolonged by all the test groups.
The EESC and EAF may help to control petit mal and grand mal seizures.
Epilepsy; China root; Smilax china; neurotoxicity
To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models.
The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison.
Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P < 0.050–0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model.
In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.
Lobelia nicotianaefolia; Lobeline; Brain GABA level; Antiepileptic activity; Pentylenetetrazol (PTZ); Strychnine
Background and purpose of the study
Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests.
The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography.
Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction.
The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.
Pentylenetetrazole; Maximal electroshock; A. obtusifolius
Flowering herbs of Gentiana olivieri Griseb. (Gentianaceae) are widely used as bitter tonic, stomachic, stimulant of appetite, antipyretic, anticonvulsant, antidiabetic and for mental problems in the different regions of Turkey.
To establish the anticonvulsant activity potential of G. olivieri.
Materials and Methods:
In this work, the ethanol extract of G. olivieri was tested in three doses (200, 750 and 1000 mg/kg) for anticonvulsant activity against seizures produced in mice by pentylenetetrazole (PTZ), picrotoxin (PIC) and maximal electroshock (MES). Neurotoxicity of the ethanol extract was also determined by the Rota rod test to evaluate the safety. Ethosuximide (150 mg/kg), diazepam (0.5 mg/kg) and carbamazepine (30 mg/kg) were used as reference drugs.
Intraperitonally, injection of the extract significantly prolonged the onset of seizures at doses of 200 and 750 mg/kg, but did not alter the incidence of PTZ-induced seizures. Onset of PIC-induced seizures was delayed by the injection of the extract (1000 mg/kg). Moreover, only 750 mg/kg of the extract protected 25% of the mice against PIC-induced seizures. On the other hand, G. olivieri extract (200, 750 and 1000 mg/kg) showed a significant protective effect against MES-induced seizures. In the Rota rod test, the ethanol extract (200 mg/kg, ip) induced disturbance in motor coordination.
The results indicate that G. olivieri has possessed anticonvulsant activity against MES-induced seizures in mice.
Anticonvulsant; Gentiana olivieri; maximum electroshock; pentylenetetrazole; picrotoxin; Rota rod
The alcoholic extract of Achyranthes bidentata (AAB) has been studied for analgesic, anticonvulsant and CNS depressant activities in animal models. Analgesic activity was studied using acetic acid-induced writing test for assessing peripheral analgesic effect and tail immersion test for central analgesic effect. Anticonvulsant activity was performed by maximal electroshock induced convulsions; while the locomotor activity was evaluated using actophotometer. AAB (250-500 mg/kg) significantly reduced the number of wriths induced by acetic acid and elevated pain threshold in hot water test. The extract (500mg/kg) exhibited anticonvulsant activity significantly (P<0.001) against tonic seizures induced by MES. The results of locomotor activity showed the significant (P<0.01) CNS depressant effect at the three doses (250,375 and mg/kg) employed. The results suggest that AAB exhibited analgesic, anticonvulsant and CNS depressant activity in a dose dependent pattern.
Achyranthes bidentata: Writhing; Tail-flick; Tonic extensor; Locomotor
Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy.
Materials and Methods:
Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD50 and CD99 values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100–300 mg/kg), lamotrigine (3–12 mg/kg) and flunarizine (5–20 mg/kg), and then each group of mice was injected with CD99 dose of PTZ (65mg/kg i.p.). Another group of mice received single ED50 dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal–Wallis ANOVA on Ranks test.
As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection.
As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish flunarizine as add-on therapy in refractory epilepsy.
Flunarizine; lamotrigine; PTZ; seizure; sodium valproate
Secondary metabolites ranging from furanone to exo-polysaccharides have been suggested to have anti-biofilm activity in various recent studies. Among these, Escherichia coli group II capsular polysaccharides were shown to inhibit biofilm formation of a wide range of organisms and more recently marine Vibrio sp. were found to secrete complex exopolysaccharides having the potential for broad-spectrum biofilm inhibition and disruption.
In this study we report that a newly identified ca. 1800 kDa polysaccharide having simple monomeric units of α-D-galactopyranosyl-(1→2)-glycerol-phosphate exerts an anti-biofilm activity against a number of both pathogenic and non-pathogenic strains without bactericidal effects. This polysaccharide was extracted from a Bacillus licheniformis strain associated with the marine organism Spongia officinalis. The mechanism of action of this compound is most likely independent from quorum sensing, as its structure is unrelated to any of the so far known quorum sensing molecules. In our experiments we also found that treatment of abiotic surfaces with our polysaccharide reduced the initial adhesion and biofilm development of strains such as Escherichia coli PHL628 and Pseudomonas fluorescens.
The polysaccharide isolated from sponge-associated B. licheniformis has several features that provide a tool for better exploration of novel anti-biofilm compounds. Inhibiting biofilm formation of a wide range of bacteria without affecting their growth appears to represent a special feature of the polysaccharide described in this report. Further research on such surface-active compounds might help developing new classes of anti-biofilm molecules with broad spectrum activity and more in general will allow exploring of new functions for bacterial polysaccharides in the environment.
The plant Synedrella nodiflora (L) Gaertn is traditionally used by some Ghanaian communities to treat epilepsy. To determine if this use has merit, we studied the anticonvulsant and other neuropharmacological effects of a hydro-ethanolic extract of the whole plant using murine models.
Materials and Methods:
The anticonvulsant effect of the extract (10–1000 mg/kg) was tested on the pentylenetetrazole-, picrotoxin-, and pilocarpine-induced seizure models and PTZ-kindling in mice/rats. The effect of the extract was also tested on motor coordination using the rota-rod.
The results obtained revealed that the extract possesses anticonvulsant effects in all the experimental models of seizures tested as it significantly reduced the latencies to myoclonic jerks and seizures as well as seizure duration and the percentage severity. The extract was also found to cause motor incoordination at the higher dose of 1000 mg/kg.
In summary, the hydro-ethanolic extract of the whole plant of S. nodiflora possesses anticonvulsant effects, possibly through an interaction with GABAergic transmission and antioxidant mechanisms and muscle relaxant effects. These findings thus provide scientific evidence in support of the traditional use of the plant in the management of epilepsy.
Kindling; pentylenetetrazole; picrotoxin; pilocarpine; Synedrella nodiflora
To study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models.
SLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively.
Substantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48% at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole.
In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.
Skimmia laureola leaves; Essential oils; Antinociceptive; Antipyretic activity
The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities.
The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on convulsive susceptibility and the anticonvulsant activity of the studied AEDs in mice, while the acute side effects of sildenafil and its combinations with the studied AEDs were evaluated in the chimney test, step-through passive-avoidance task and grip-strength test in mice. Total brain concentrations of AEDs were also determined. Sildenafil (5–40 mg/kg) did not influence the threshold for PTZ-induced clonic seizures in mice, but increased the anticonvulsant activity of ETS in this test without any significant changes in the total brain concentration. The activity of the remaining AEDs was not significantly changed by sildenafil. Neither sildenafil alone nor its combinations with the studied AEDs produced any changes in the motor coordination, long-term memory and muscular strength in mice. Co-administration of sildenafil with ETS in male epileptic patients with co-existing erectile dysfunctions might lead to the pharmacodynamic interactions that may be beneficial for the patients. Combinations of sildenafil with CZP, VPA, PB and TGB appear to be neutral in terms of their influence on seizures.
Sildenafil; Epilepsy; Pentylenetetrazole; Clonic seizures; Seizure models; Antiepileptic drugs; Mice
Indigofera tinctoria Linn. of Fabaceae family is claimed to be useful to control epileptic seizures in the Indian system of folkore medicine. This study was designed to evaluate tinctoria and to verify the claim.
Materials and Methods
Seizures were induced in male albino rats with pentylenetetrazole (PTZ). The test group animals were administered ethanolic extract of Indigofera tinctoria (EEIT) orally. The time of onset and duration of clonic convulsions were recorded. Maximal electroshock seizures (MES) were induced in animals. The duration of hind limb tonic extension (HLTE) was recorded. GABA levels and GABA transaminase activity in brain were estimated.
In PTZ model, EEIT significantly (P< 0.01, P< 0.001) delayed the onset of convulsions and reduced the duration of seizures in a dose dependent manner. A significant (P< 0.05) reduction in the duration of HLTE at higher doses of EEIT was observed in MES model. Increase in brain GABA levels was observed on treatment with EEIT at 500 and 1000 mg/kg doses, suggested that the plant may be acting by facilitating GABAergic transmission. A significant reduction (P< 0.05) in the activity of brain GABA transaminase was observed at higher doses. No neurotoxic signs were observed with rotarod test, pentobarbital induced sleeping time, locomotor activity and haloperidol-induced catalepsy.
The ethanolic extract of tinctoria was found to be useful to control and treat the variety of seizures.
Clonic seizures; GABA; GABA-T; Hind limb tonic extension; Indigofera tinctoria; MES; Neurotoxic; PTZ
Objective: To study the effect of halo substitution on disubstituted aryl semicarbazones on the anticonvulsant potential and model the activity based on quantum mechanics. Methods: A series of twenty-six compounds of N4-(4-bromo-3-methylphenyl) semicarbazones were synthesized and evaluated for the anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential compounds were also tested in the subcutaneous strychnine (scSTY) and subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized compounds were tested for behavioral impairment and CNS (central nervous system) depression in mice. Quantum mechanical modelling was carried out on these compounds to gain understanding on the structural features essential for activity. Results: Some compounds possessed broad spectrum anticonvulsant activity as indicated by their effect in pentylenetetrazole, strychnine, picrotoxin and maximal electroshock seizures models in resemblance to other aryl semicarbazone derivatives reported earlier. The higher the difference in HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels was, the greater was the activity profile. Conclusion: The pharmacophoric requirements for compounds to exhibit anticonvulsant activity that includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an electron donor have been justified with the molecular orbital surface analysis of the synthesized compounds.
Anticonvulsants; Aryl semicarbazones; Quantum mechanics (QM); Molecular orbital surfaces
Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N6-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.
Background: There have been some reports about the possible N-methyl-D-aspartate (NMDA) antagonist activity of Guaifenesin. As drugs with a similar structure to Guaifenesin (i.e. Felbamate) and those with NMDA antagonist activity have been clinically used as anticonvulsants, the aim of this study was to determine whether Guaifenesin has an anticonvulsant effect in an animal model of seizure.
Methods: Anticonvulsant effect of Guaifenesin was assessed via Pentylenetetrazol (PTZ)-induced convulsion. Male albino mice received Guaifenesin (100, 200, 300, or 400 mg/kg; n=8-10) or 0.25% Tween (vehicle) intraperitoneally 30 minutes before the injection of PTZ (95 mg/kg). Diazepam (3 mg/kg; n=8) was used as a reference drug. The latency time before the onset of myoclonic, clonic, and tonic-clonic convulsions, percentage of animals exhibiting convulsion, and percentage of mortality were recorded. In addition, the effect of Guaifenesin on neuromuscular coordination was assessed using the Rotarod.
Results: Guaifenesin at all the studied doses significantly increased the latency to myoclonic and clonic convulsions in a dose-dependent manner. In addition, Guaifenesin at the dose of 300 mg/kg increased the latency to tonic-clonic seizure. The ED50s of Guaifenesin for protection against PTZ-induced clonic and tonic-clonic seizures and death were 744.88 (360-1540), 256 (178-363), and 328 (262-411) mg/kg, respectively. Guaifenesin at all the investigated doses significantly reduced neuromuscular coordination, compared to the vehicle-treated group.
Conclusion: These results suggest that Guaifenesin possesses muscle relaxant and anticonvulsant properties and may have a potential clinical use in absence seizure.
Guaifenesin; Anticonvulsant; Pentylenetetrazol
Euphorbia pulcherrima (EP) belongs to the family: Euphorbiaceae and Genus: Euphorbia. Many species of Euphorbia have been reported as having beneficial properties like anticonvulsive effect, central analgesic properties, antipyretic action, central depressant action and strong sedative effect. However, little study has been done and published on EP.
To observe and evaluate various neuropharmacological effects like antinociceptive effect, anticonvulsant effect, motor in-coordination, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats.
Setting and Design:
Quantitative experimental study in mice and rats by various experimental models.
Materials and Methods:
Different experimental models were used to assess the antinociceptive effect (hotplate, tail flick and acetic acid induced writhing test), anticonvulsant effect (Maximal Electroshock Seizure test [MES] and Pentylenetetrazole induced seizures [PTZ]), motor in-coordination effect (Rota rod test), pentobarbital induced sleeping time and behavioral responses of EP in mice and rats after oral administration of EP crude dried extracts in three different doses (250, 500 and 1000 mg/kg).
Statistical Analysis Used:
The significance of difference with respect to control was evaluated using the Mann-Whitney U test. A probability (P-value) level less than 0.05 was considered as significant.
In MES test model, duration of tonic hind limb extension in mice treated with EP was significantly less as compared to vehicle treated group. EP was most effective in a dose of 1000 mg/kg. There was also significant increase in the latency and decrease in the incidence of convulsions with the use of EP in three different doses in PTZ induced seizure model.
This study showed EP (crude dried) extracts to possess anticonvulsant properties but no effect on motor co-ordination and anxiety.
Anticonvulsant effect; antinociceptive effect; anxiolytic; pentobarbital induced sleeping time; sedative
The aim of the present study was to evaluate the sedative and antiepileptic activities of ethanolic extract of Anthocephalus cadamba (ACE) bark in various experimental animal models.
Materials and Methods:
ACE was tested at three doses viz. 100, 200 and 400 mg/kg p.o. We used ketamine-induced sleeping time model to test the sedative property of the extract where, onset and duration of sleep were observed. A paradigm of anticonvulsant models (pentylenetetrazole, isoniazid and maximal electroshock-induced seizures) were used to evaluate its protective effect against absence and generalized types of seizures. Onset of clonic convulsions, tonic extension and time of death were observed in PTZ and INH-induced seizure models. In MES model, duration of tonic hind leg extension and onset of stupor were observed.
ACE showed significant increase in ketamine induced sleeping time. It also exhibited significant increase (P<0.05, 0.01 and 0.001) in latency to clonic convulsion, tonic extension and time of death in PTZ and INH models at all tested doses, whereas in the MES model, the lower dose was found to be effective when compared with the higher doses (200 and 400 mg/kg, p.o.).
The results of the present investigation demonstrated that ACE possesses sedative and antiepileptic activities.
Anthocephalus cadamba; isoniazid; maximal electro shock; pentylenetetrazole; sedation; seizures
The present study was focused on evaluating the potential of Emblica officinalis against cariogenic properties of Streptococcus mutans, a causative microorganism for caries. The effect of crude extract and ethanolic fraction from Emblica officinalis fruit was analysed against S. mutans. The sub-MIC concentrations of crude and ethanolic fraction of E. officinalis were evaluated for its cariogenic properties such as acid production, biofilm formation, cell-surface hydrophobicity, glucan production, sucrose-dependent and independent adherence. Its effect on biofilm architecture was also investigated with the help of confocal and scanning electron microscopy (SEM). Moreover, expression of genes involved in biofilm formation was also studied by quantitative RT- PCR. This study showed 50% reduction in adherence at concentrations 156 µg/ and 312.5 µg/ml of crude extract and ethanolic fraction respectively. However, the biofilm was reduced to 50% in the presence of crude extract (39.04 µg/ml) and ethanolic fraction (78.08 µg/ml). Furthermore, effective reduction was observed in the glucan synthesis and cell surface hydrophobicity. The qRT-PCR revealed significant suppression of the genes involved in its virulence. Confocal and scanning electron microscopy clearly depicted the obliteration of biofilm structure with reference to control. Hence, this study reveals the potential of E. officinalis fruit extracts as an alternative and complementary medicine for dental caries by inhibiting the virulence factors of Streptococcus mutans.
Toxins derived from jellyfishes have been exploited as a model for the development of new drug promising applications to treat neurodegenerative diseases. The present work is aimed to evaluate the acute toxicity of crude venom of Pelagia noctiluca and then to screen the analgesic and antibutyrylcholinestrasic (anti-BuChE) activities of the crude venom and its fractions.
Sephadex G75 gel was used to separate crude venom of Pelagia noctiluca, which led to some fractions. In addition, in vivo analgesic and in vitro plasma antibutyrylcholinestrasic activities were carried out with Pelagia crude venom and its fractions respectively.
The crude venom and its fractions displayed analgesic and anti-BuChE activities at different doses without inducing acute toxicity. Fraction 2 possesses the highest analgesic and antibutyrylcholinestrasic properties. The crude venom and fraction 1 had shown to possess less significant inhibitory activity against analgesic and antibutyrylcholinestrasic models.
Based on this study, the crude venom of Pelagia noctiluca is found to be a useful tool for probing pharmacological activity. The purification and the determination of chemical structures of compounds of active fractions of the venom are under investigation.
Pelagia noctiluca; Venom; Jellyfish; Analgesic activity; Anti-Butyrylcholinesterasic activity
To study the effect of calcium channel blockers (CCBs) cinnarizine and nifedipine on maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED).
Materials and Methods:
For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg), nifedipine (5 mg/kg), sodium valproate (300 mg/kg) and carbamazepine (8 mg/kg) alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher’s exact test (Ovvind Langsrud software, German version).
In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures.
The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.
Carbamazepine; cinnarizine; nifedipine; seizures; sodium valproate
Clavulanic acid (CLAV) inhibits bacterial β-lactamases and is commonly used to aid antibiotic therapy. Prompted by the initial evidence suggestive of the potential anticonvulsant and neuroprotective properties of CLAV, the present study was undertaken to systematically evaluate its acute effects on seizure thresholds in seizure tests typically used in primary screening of potential antiepileptic drugs (AEDs). In the present study, 6-Hz seizure threshold, maximal electroshock seizure threshold (MEST) test, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests were used to determine anticonvulsant effects of intraperitoneally (i.p.) administered CLAV in mice. Acute effects on motor coordination and muscle strength were assessed in the chimney and grip-strength tests, respectively. Doses of CLAV studied in the present study were either comparable or extended the doses reported in the literature to be effective against kainic acid-induced convulsions in mice or behaviorally active in rodents and monkeys. CLAV had no effect on seizure thresholds in the 6-Hz (64 ng/kg to 1 mg/kg) and MEST (64 ng/kg to 5 mg/kg) seizure tests. Similarly, CLAV had no effect on seizure thresholds for i.v. PTZ-induced myoclonic twitch, clonic convulsions, and tonic convulsions (64 ng/kg to 5 mg/kg). Finally, CLAV (64 ng/kg to 5 mg/kg) had no effect on the motor performance and muscle strength in the chimney and grip-strength tests, respectively. In summary, CLAV failed to affect seizure thresholds in three seizure tests in mice. Although the results of the present study do not support further development of CLAV as an AED, its beneficial effects in chronic epilepsy models warrant further evaluation owing to its, for example, potential neuroprotective properties.
Pentylenetetrazole; 6-Hz seizure; Maximal electroshock; Seizure threshold; Antiepileptic drugs; β-Lactamase inhibitor
The progesterone derivative allopregnanolone (ALLO) rapidly potentiates γ-aminobutyric acidA (GABAA) receptor mediated inhibition. The present studies determined whether specific manipulation of neurosteroid levels in the hippocampus would alter seizure susceptibility in an animal model genetically susceptible to severe ethanol (EtOH) withdrawal, Withdrawal Seizure-Prone (WSP) mice. Male WSP mice were surgically implanted with bilateral guide cannulae aimed at the CA1 region of the hippocampus one week prior to measuring seizure susceptibility to the convulsant pentylenetetrazol (PTZ), given via timed tail vein infusion. Bilateral intra-hippocampal infusion of ALLO (0.1 g/side) was anticonvulsant, increasing the threshold dose of PTZ for onset to myoclonic twitch and face and forelimb clonus by 2–3 fold. In contrast, infusion of the 5α-reductase inhibitor finasteride (FIN; 2 g/side), which decreases endogenous ALLO levels, exhibited a proconvulsant effect. During withdrawal from chronic EtOH exposure, WSP mice were tolerant to the anticonvulsant effect of intra-hippocampal ALLO infusion, consistent with published results following systemic injection. Finally, administration of intra-hippocampal FIN given only during the development of physical dependence significantly increased EtOH withdrawal severity, measured by handling-induced convulsions. These findings are the first demonstration that bi-directional manipulation of hippocampal ALLO levels produces opposite behavioral consequences that are consistent with alterations in GABAergic inhibitory tone in drug naïve mice. Importantly, EtOH withdrawal rendered WSP mice less sensitive to ALLO’s anticonvulsant effect and more sensitive to FIN’s proconvulsant effect, suggesting an alteration in the sensitivity of hippocampal GABAA receptors in response to fluctuations in GABAergic neurosteroids during ethanol withdrawal.
allopregnanolone; GABAA receptors; finasteride; pentylenetetrazol; 5α-reductase; ethanol; withdrawal
Anticonvulsant and anxiolytic activities of leaf extracts and fraction of Ocimum gratissimum L. (Lamiaceae) were studied using seizures induced by pentylenetetrazol and open-field tests in mice. The results showed that the extracts and fraction increased the latency of tonic and tonic-clonic seizures and death and elicited 50% protection against mortality. In the open-field test, the extracts and fraction decreased the frequency of line crossing, center square entries, rearing against a wall and grooming, whereas grooming duration and freezing frequency and duration were increased. Acute toxicity test in mice gave an oral LD50 greater than 5000 mg/kg for the methanol extract. These findings suggest that extracts of this plant possess anticonvulsant and anxiolytic-like properties.
Anticonvulsant; anxiolytic; Ocimum gratissimum; open field