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Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced seizure: A behavioral and EEG study in rats
Abstract
Marsilea quadrifolia Linn (MQ) extract has been used traditionally as sedative and antiepileptic drug in India.
To investigate the anticonvulsive potential of MQ extracts by using behavior and electroencephalographic (EEG) analysis on pentylenetetrazole (PTZ) induced seizure model in rats.
For anticonvulsant effect, 60minutes after administration of MQ, behavior and EEG were analyzed during PTZ (60mg/kg) induced seizures. Changes of EEG power, latency of onset of seizure, seizure severity score, and duration of epileptic seizure were determined.
Both the water and ethanol extract of MQ increased the latency of seizure but also decreased duration of epileptic seizure and seizure severity score. This reduction of seizure severity was also observed in EEG recording and EEG power analysis. The effectiveness of MQ ethanol extract is better than MQ water extract.
Both water and ethanol extract of MQ were effective in reducing the severity of behavioral and EEG seizures induced by PTZ in rats. This study justifies the traditional use of this plant in epilepsy.
... Some medicinal plants have shown potential as new, safe treatment options [11,12]. Although many of them have traditionally been used as sedative and antiepileptic agent, there is still lack of controlled experimental reports on therapeutic use [13]. Stringer [14] states that more than 50 plants have shown some anticonvulsant activity whereas Xiao et al. [15] noted that 23 botanicals were used in Chinese traditional medicine to treat epilepsy but none of them has been developed into a standard medication for the treatment of seizures. ...
... Positive results in either model suggest that the test compound, or its metabolite crossed the blood-brain barrier and exerted its effect in the central nervous system [1]. In this review, all experiments consisted initially of phenotypic screens in rodents using predominantly PTZ [6,13,18,19,21,22,24,25,27,28], MES [20,22,24] and pilocarpine [16,23,26,32] seizure models. A few researchers dared to test their extracts in more than one phenotypic screening models [13,20,22,24]. ...
... In this review, all experiments consisted initially of phenotypic screens in rodents using predominantly PTZ [6,13,18,19,21,22,24,25,27,28], MES [20,22,24] and pilocarpine [16,23,26,32] seizure models. A few researchers dared to test their extracts in more than one phenotypic screening models [13,20,22,24]. There is considerable concern among AED researchers that the limited models being used only identify me-too drugs that act by the same old physiological mechanisms, thus limiting chances of discovering novel therapies with different targets [38,39], especially compounds with efficacy against drug-resistant seizures. ...
Background:
Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. The limited supply, high cost as well as low efficacy and adverse side effects of antiepileptic drugs (AEDs) is a matter of major concern. Herbal medicine has always been traditionally part of treatment of epilepsy. Herbal medicines are generally well tolerated, with fewer side effects.
Method:
To highlight some herbal extracts that have been studied for their anticonvulsant activity in animal models, literature search from PubMed and Science Direct, was performed. The keywords for the search consisted of combinations of the following terms: Herbal antiepileptic and/or anticonvulsant, botanicals + epilepsy. Literature published in the last five years was considered.
Results:
Eighteen (18) anticonvulsant herbal agents are reported and discussed. Experiments mostly consisted of phenotypic screens in rodents, with little diversity in screening methods. In most experiments, the tested extracts prolonged the time to onset of seizures and decreased their duration. Most experimenters implicate potentiation of GABAergic activity as the mode of action of the extracts, even though some experimenters did not fully characterise the bioactive chemical composition of their extracts.
Conclusion:
Potential herbal remedies have shown positive results in animal models. It remains unclear how many make it into clinical trials and eventually making part of the AED list. More rigorous research, applying strict research methodology with uniform herbal combinations, as well as clinical studies are urgently needed.
... It is a famine food and only used during food scarcity. [196,198,199,200], antidiarrheal [194], antifungal [201], analgesic [194], anti-inflammatory [202], antioxidant [203,204], antidiabetic [205], anti-Alzheimer's [206,207], antiepileptic [208], anticonvulsive [209], nephroprotective [210] and antitumor [211] activities. 5.7.1.5. ...
... Antioxidant and anticancer D. boryana Aerial part [92,94] D. esculentum Leaf [101,102,103,104,105] D. maximum Frond [121] S. palustris Frond [129,130,131] W. unigemmata Aerial part [137,138] C. spinulosa Leaf [144] D. cochleata Leaf [166] P. squarrosum Leaf [165] M. quadrifolia Aerial part, leaf [203,204,211] N. cordifolia Fruit, leaf [223] H. zeylanica Rhizome [242,243] C. thalictroides Frond [275] P. biaurita Frond [278] T. gemmifera Rhizome, leaf, twig [295,297,298] T. zeylanica Leaf [303] 10 Neuroprotective D. esculentum Leaf [104] C. spinulosa Leaf [144] L. japonicum Spore [186] M. quadrifolia Whole plant, leaf [206,207,208,209] 11 Nephroprotective M. quadrifolia Leaf [210] N. cordifolia Rhizome [225] 12 Hepatoprotective D. esculentum Leaf [103] L. flexuosum Whole plant [176,177] H. zeylanica Rhizome [236,237] 13 Antifertility L. flexuosum Not specified [174,175] G.B. Bajracharya, B. Bajracharya Heliyon 8 (2022) e11687 ...
Ferns are used as traditional and fascinating foods in many countries. They are also considered to possess important ethnomedicinal values; however, ferns are one of the underutilized plant resources by both scientific and local communities. Pharmagonostical studies reveal that ferns and fern-allies possess several biological activities including antibacterial, antiviral, antifungal, antimalarial, antidiarrheal, anthelmintic, analgesic, anti-inflammatory, antidiabetic, anticancer, neuroprotective, nephroprotective, hepatoprotective, antifertility, etc. Flavonoids and terpenoids are major secondary metabolites present in ferns. Ugonins, particularly isolated from Helminthostachys zeylanica, have found diverse bioactivities. Ptaquiloside, a norsesquiterpene glucoside, found in Pteridium revolutum, Dryopteris cochleata and Polystichum squarrosum, is one of the hazardous metabolites of ferns which is responsible for the toxic effect. Alkaloids are reported to be present in the ferns; however, the qualitative data are uncertain. Some fern metabolites, such as cyanogenic glycosides and terpenoids, are considered to possess defensive activity against animal attacks. Some ferns are also used for manuring as biological alternative to pesticides. Nepalese have consumed at least 33 species of ferns and fern-allies belonging to 13 families, 20 genera as cooked vegetable foods. The aim of this review is compilation of information available on their distribution, ethnomecinal values, pharmcognosy, pharmacology and phytochemistry.
... It is a famine food and only used during food scarcity. [196,198,199,200], antidiarrheal [194], antifungal [201], analgesic [194], anti-inflammatory [202], antioxidant [203,204], antidiabetic [205], anti-Alzheimer's [206,207], antiepileptic [208], anticonvulsive [209], nephroprotective [210] and antitumor [211] activities. 5.7.1.5. ...
... Antioxidant and anticancer D. boryana Aerial part [92,94] D. esculentum Leaf [101,102,103,104,105] D. maximum Frond [121] S. palustris Frond [129,130,131] W. unigemmata Aerial part [137,138] C. spinulosa Leaf [144] D. cochleata Leaf [166] P. squarrosum Leaf [165] M. quadrifolia Aerial part, leaf [203,204,211] N. cordifolia Fruit, leaf [223] H. zeylanica Rhizome [242,243] C. thalictroides Frond [275] P. biaurita Frond [278] T. gemmifera Rhizome, leaf, twig [295,297,298] T. zeylanica Leaf [303] 10 Neuroprotective D. esculentum Leaf [104] C. spinulosa Leaf [144] L. japonicum Spore [186] M. quadrifolia Whole plant, leaf [206,207,208,209] 11 Nephroprotective M. quadrifolia Leaf [210] N. cordifolia Rhizome [225] 12 Hepatoprotective D. esculentum Leaf [103] L. flexuosum Whole plant [176,177] H. zeylanica Rhizome [236,237] 13 Antifertility L. flexuosum Not specified [174,175] G.B. Bajracharya, B. Bajracharya Heliyon 8 (2022) e11687 ...
... It has been used as a folk or traditional remedy for liver diseases, convulsion, insomnia, microbial infections, piles, kidney infection, hepatitis, epilepsy, bronchitis, diarrhoea, obesity and inflammation. It is also used as analgesic and blood purifier (Sahu et al., 2012;Balne et al., 2013). Ethanolic extract of M. minuta (Marsileaceae) (400 mg/kg/day, p.o., for 3 days) administration significantly reduced the activity of AChE in the hippocampus, frontal cortex and hypothalamus of scopolamine-treated mice resulted in attenuation of associative memory deficit (Bhattamisra et al., 2012). ...
... In traditional system of medicine, M. minuta (Marsileaceae) is used to alleviate liver disease, convulsion, insomnia, microbial infections, piles, kidney infection, hepatitis, epilepsy, bronchitis, diarrhoea, obesity and inflammation. It is also used as analgesic and blood purifier (Sahu et al., 2012;Balne et al., 2013). Ethanolic extract of M. minuta (400 mg/kg/day, p.o., for 3 days) administration significantly reduced the activity of AChE in the hippocampus, frontal cortex and hypothalamus of scopolamine-treated mice, resulted in attenuation of associative memory dysfunction (Bhattamisra et al., 2012). ...
Alzheimer’s disease, a progressive neurodegenerative disease, is characterised by hypofunction of acetylcholine (ACh) neurotransmitter in the distinct region of brain. Acetylcholinesterase (AChE) is an enzyme that metabolises the ACh at synaptic cleft resulting in Alzheimer’s disease. Medicinal plants have been used to treat numerous ailments and improve human health from ancient time. A traditional system of medicine is long recognised for its effective management of neurological disorders. The present review confers the scope of some common medicinal plants with a special focus on AChE-mediated central nervous system complications especially Alzheimer’s disease. Literature suggests that medicinal plants reduce neuronal dysfunctions by reducing AChE activity in different brain regions. In some instances, activation of AChE activity by medicinal plants also showed therapeutic potential. In conclusion, medicinal plants have a wide scope and possess therapeutic potential to efficiently manage neurological disorders associated with AChE dysregulation.
... 18 Evaluation of anticonvulsant activity of chrysin (2.5, 5, and 10 mg/kg; p.o.) in PTZ challenged rats For electroencephalogram (EEG) recording, two stainless steel screw electrodes were implanted stereo- taxically (Quintessential stereotaxic injector Stoelting Co., Wood Dale, IL, USA) over visual cortex (6.0 mm posterior to the bregma and 3.5 mm lateral to the midline on both sides) and another electrode (11 mm anterior to the bregma on the midline served as ground) under intraperitoneal thiopentone anesthe- sia (40 mg/kg, i.p.) to 25 animals. 19 Thereafter, elec- trodes were soldered to a miniature socket and the whole assembly was anchored to the skull with dental acrylate. After 72 h, all animals were randomly divided into five groups of five rats each. ...
... Epoch length of 10 s was recorded in two phases: first during behavioral tonic-clonic seizure and second during maximum EEG activity where tonic-clonic seizure was not observed (between 3 and 10 min after PTZ injection). 19 The animals were sacrificed by decapitation following EEG recording. The brain was excised and microdis- sected into the hippocampus, cerebellum, and cerebral cortex and were stored at -80°C for future studies. ...
Objective: The traditional use of the ethanolic extract of the fruit of Pyrus pashia (EPP) as a potential anticonvulsant was validated using experimental animal models. Furthermore, the anticonvulsant activity of isolated chrysin was investigated against experimental animal models to draw a possible therapeutic mechanism of EPP. Additionally, the safety profile of chrysin was evaluated to explore the possible therapeutic alternative in the management of epilepsy.
Method: The anticonvulsant activity in terms of duration of onset of hind limb tonic extension and convulsion of standardized EPP was evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) model of experimental epilepsy respectively. Furthermore, the anticonvulsant activity and electrophysiological properties of chrysin was investigated in addition to antioxidant activity against PTZ-induced convulsion in experimental animals. Moreover, the neurotoxic profile of the chrysin was assessed in terms of duration of movement and running in photoactometer and rotarod apparatus, respectively.
Results: EPP (100, 200, and 400 mg/kg) exhibited significant anticonvulsant activity against an acute model of MES and PTZ-induced convulsions in experimental animals. Furthermore, chrysin (2.5, 5, and 10 mg/kg) also exhibited significant anticonvulsant activity against PTZ-induced convulsions in rats. In addition, chrysin did not exhibit sedative-like behavior in experimental rodents.
Discussion: EPP could be considered as a potential and alternative therapeutic option in the management of epilepsy.
... Many preclinical studies have been reported using epileptic models by giving herbs (anticonvulsant activity) for the treatment of epilepsy as listed in Table 1. [55][56][57][58][59][60][61][62][63][64][65][66][67] Several herbs have been tested in various animal models like Maximal Electroshock (MES) administered, and treated with pentylenetetrazol (PTZ), kainic acid and picrotoxin. However, the efficacy of herbal extract treatment in pilocarpine-induced model of TLE-HS has not been well studied. ...
Background and objectives:
Epilepsy is a neurological disorder in which the patient suffers with two or more unprovoked seizures. It is one of the most common neurological disorders worldwide, affecting more than 70 million people. Currently various modes of effective treatments are available, but still there are many cases that remain drug resistant. Hence, there is a need to explore herbal medications for the treatment of drug resistant epilepsy.
Methods:
Recent reviews and research articles (2000-2022) from PubMed and Google Scholar have been explored.
Review:
Based on etiology, there are six categories of epilepsy: Genetic, structural, metabolic, immune, infectious, and unknown epilepsy. Temporal lobe epilepsy with hippocampus sclerosis (TLE-HS) is one of the most common forms of structural epilepsy. Even though several new anti-epileptic drugs (AEDs) have been discovered, but the treatment of some cases especially TLE-HS remains resistant to them. Surgery is one of the most effective options for TLE-HS; however, this usually results in memory deficits, and occasionally, intracranial hematoma, delayed hydrocephalus, subdural empyema, and visual field defects in patients.
Conclusion:
Hence, to overcome drug resistance, new pharmacological and herbal therapies are required. Animal trials are first step in the development of new drugs, to study toxicity and efficacy of proposed drugs. Many herbs have anticonvulsant activity but remain an under-explored treatment option for epilepsy. Further research on herbal extracts as a possible treatment for epilepsy needs to be conducted.
... Another variable evaluated was the severity of epilepsy; no significant difference was seen among the groups (Fig. 6). In fact, PTZ causes seizure through GABA A receptor [25,27]. When this receptor is active, its chloride channel is open and leads to chlorine ion flow and nervous hyperpolarization [8]. ...
Background
The aim was to evaluate the protective effect of hydroalcoholic extract of Anacyclus pyrethrum root (APE) against pentylenetetrazole (PTZ) drug which is used for inducing epileptic seizures in animal model.
Results
50 male rats were divided: control (without any intervention), positive control 1st (received PTZ 60 mg/kg, IP), first experimental group (PTZ + Extract 500 mg/kg, gavages, 30 min before PTZ), positive control 2nd (PTZ + Phaclofen, 200 µg/µl, ICV), and second experimental group (PTZ + extract 500 mg/kg, gavage, 30 min before PTZ + Phaclofen 200 µg/µl, ICV). Several parameters were assessed during 20 min and followed up for 1.5 h. Then, the data were analyzed. APE with a dose of 500 mg/kg increased the latency time of seizures in the first experimental group, compared to the positive control 1st, also, comparison of different groups in terms of Seizure Score at the 1st time (severity of first attack) had no significant difference ( P -value = 0.51, P -value = 0.34). The mean of seizure attacks (event number) was significant between the first and second positive control groups ( P -value = 0.01) and also between the second positive control and the first experimental group ( P -value = 0.011). Significant changes were observed in the mean score of the first and second positive control groups ( P -value = 0.001) and the first experimental and second positive control groups ( P -value = 0.003). In addition, the second experimental group had significant changes compared to the first positive control group ( P -value = 0.014), However, no significant changes were observed between the positive control and experimental groups in terms of the severity of seizures.
Conclusion
Results have shown both blocked GABAergic receptors A and B involved in epileptic seizures. In addition, APE root increased delay time of epileptic seizures, as well as reduces epileptic seizure in dose response state.
... The spores are released out by swelling the sporocarps. The plant has been reported to have anti-epileptic, [3] anticonvulsant, [4] anticancer, anti-bacterial, [5] antifungal, [5] and anti-inflammatory activities. [6] Traditionally the plant is widely used in all over India, petiole and leaves are cooked in oil with salt and masalas for the treatment of headache, hypertension and sleep disorders. ...
... izures, low cost as well as reduced or no unpleasant effects. Some medicinal plants have demonstrated ability as new, safe treatment alternatives (Kakooza-Mwesige, 2015). Many species of aromatic plants have been used ethnomedicinally as sedative and antiepileptic agents but there is still lack of controlled experimental reports on therapeutic use (Sahu et. al., 2012). Essential oils have been used in places with rich cultures like India, Brazil, China and the Middle East in managing convulsive disorders (Debas et al., 2006). They have also been researched and documented for their sedative, anxiolytic and neuroprotective activities (De Sousa et al., 2015;Abuhamdah et al., 2015). Several compounds hav ...
The use of medicinal plants is on the rise due to the increase of various diseases and shortcomings of orthodox medicine. For many ailments including convulsion, conventional medicine has not been able to find a lasting solution. This study was directed towards assessing the ethnomedicinal use of Callistemon citrinus leaves in the management of convulsion. The volatile oil of the leaves was extracted and an acute toxicity test was carried out following Lorke’s description. Maximal electroshock (MES), strychnine and pentylenetetrazol anticonvulsant methods were used. Separate groups of albino mice were given 200, 400 and 800 mg/kg doses of the volatile oil. Drug solutions; 30 mg/kg phenobarbitone for MES and 2 mg/kg diazepam for strychnine and pentylenetetrazol models were administered as a positive control. The start of tonic leg extension, duration and percentage mortality was recorded. Doses of 200 and 400 mg/kg significantly (P<0.05) inhibited seizure in the mice with scores of 40 % each in the MES model. There was a dose-dependent reduction in the duration of seizures with 68.47, 70.27 and 81.08 % reductions in the pentylenetetrazol model. No significant coverage was given in the strychnine model. C. citrinus oil protected the mice against pentylenetetrazol and maximal electroshock-induced convulsion hence could contribute to the medical treatment of epilepsy.
... Similarly, Marsilea quadrifolia in PTZ-induced seizure rat model was found to significantly increase the latency to seizure when compared to diazepam. It also decreased the seizure severity score and duration of epileptic seizures [83]. Passiflora incarnata in male albino Swiss mice decreased the seizure severity score, showing similar effects as diazepam [84]. ...
Herbal medicines are being used since ancient times and is an important part of alternative and traditional medicinal system. In recent decades scientists are embracing herbal medicines based on the fact that a number of drugs which are currently in use are derived directly or indirectly from plant sources. Moreover, herbal drugs have lesser side effects albeit are potentially strong therapeutic agents. The herbal medicine market is estimated to be around US $62 billion market globally. Herbal medicine has gained widespread acceptance due to its low toxicity, low cost, ease of accessibility and efficacy in treating difficult diseases. Safety and efficacy are another important factor in the commercialization process of herbal medicines. Nanotechnology have been shown to be potentially effective in improving the bioactivity and bioavailability of herbal medicines. Development of nano-phytomedicines (or by reducing the size of phytomedicine), attaching polymers with phytomedicines and modifying the surface properties of herbal drugs, increased the solubility, permeability and eventually the bioavailability of herbal formulations. Novel formulations such as niosomes, liposomes, nanospheres, phytosomes etc. can be exploited in this area. This article reviews herbal medicines which have prominent activity in Central Nervous System (CNS) disorder and reported nano-phytomedicines based delivery systems. Keywords: Nano formulation, phytomedicine, central nervous system, neurodegenerative disorder, nano-phytomedicines, herbal medicine.
... Kannada: Neer, hurali). It has been reported to have many medicinal properties (anti-inflammatory, anti-venom and applied to abscesses, depurative, refrigerant and diuretic etc) (Vent et al., 1985) .The aerial parts have been found to possess antidiabetic activity (Zahan et al 2011), antibacterial, antioxidant and cytotoxic activity (Ripa et al., 2009), anticonvulsant (Sahua et al., 2012), anticholinesterase potential (Bhadra et al., 2012), neurodegenerative disorders (Ashwinietal.,2012), psychopharmacological action (Reddy et al., 2012). ...
... This study justifies the traditional Bengali use of this plant as a sedative. 29 Anxiolytic activity: Study revealed that the different fractions of Enhydra fluctuans aerial parts possess central nervous system depressant activity. The effect of the three fractions of Enhydra fluctuans on central and peripheral nervous system by using spontaneous motor activity, sedative activity, anticonvulsant property, anti-stress activity by tail suspension test (TST) and forced swimming test (FST). ...
Religious traditions are the backbone of anthropological knowledge for any country. Sometimes in disguise they become an integral part for the general wellbeing for a specific community. The tradition of taking 'Choddoshak' (leaves of fourteen leafy vegetables) during the season of autumn by Bengali people of West Bengal, India and Bangladesh may be a ritualistic event by them but in contrary this fourteen herbs may have synergistic effect to collectively fight against the common health problems that occur particularly during the season of autumn. This review discusses the possible eth-no pharmacological role and pharmacology of the individual plants of ChoddoShak and helps to justify the intake of ChoddoShak in the particular season of autumn by Bengali community.
... [55] Marsileaquadrifolia Linn showed antiepileptic properties in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy. [56,57] Black seed oil showed promising clinical outcome as adjuvant therapy in intractable epilepsies. [58] Trichosanthestricuspidata modulated oxidative toxicity in brain hippocampus against pilocarpine-induced status epilepticus in mice. ...
There are more than 10 million persons with epilepsy (PWE) in India. Despite availability of antiepileptic drugs (AEDs), there is a large treatment gap varying from 50 to 70% among PWE. For treatable epilepsy, this gap can be attributed to poor education, poverty, cultural beliefs, stigma, and poor healthcare infrastructure; whereas for chronic epilepsy, this gap can be attributed to lack of proper diagnosis and treatment. To prevent, treat, and cure epilepsy, researchers worldwide have made exciting advances across all areas of epilepsy research. Studies carried out in India have also shown substantial progress; however, most of them are focused on the epidemiological aspects of epilepsy, genetic associations, identification, and validation of new AEDs in animal models of epilepsy.Very few studies are reported on understanding the process of epileptogenesis, a dynamic process by which neurons begin to display abnormal firing patterns that cause epileptic seizures. Animal epilepsy models can be used for in depth studies; however, studies conducted on resected brain tissues from epilepsy patients are clinically relevant. Finally, more funding support from government and collaborations among basic research institutes, medical institutes, as well as industries is required to raise the standards of epilepsy research in India.This review focuses on the evaluation of the current status of epilepsy research in India and the need to identify potential anti-epileptogenic interventions.
... Epilepsy is one of the most common and widespread neurological disorders in the human population (Surajit et al., 2012).In modern medicine, epilepsy is considered to be a chronic brain syndrome of various etiology characterized by recurrent seizures and usually associated with loss or disturbance of consciousness. ...
Modern drug therapy of epilepsy is complicated by the inability of drugs to control seizures in some patients and side effects that range in severity from minimal impairment of the central nervous system to death from aplastic anemia or hepatic failure. Medicinal plants used in traditional medicine for the treatment of epilepsy have been scientifically shown to possess promising anticonvulsant activities in animal models for screening for anticonvulsant activity and can be a source of newer anticonvulsants. The aim of this study was to investigate the preliminary phytochemical properties, anticonvulsant and anxiolytic activities of Melanthera scandens aqueous and ethanolic extracts. Phytochemicals from the aqueous and ethanolic extracts were screened by standard methods. Anticonvulsant activity was evaluated against pentylenetetrazol (PTZ)-induced seizure model in rats. The effect of the extract at oral dose levels of 250, 500 and 1000 mg/kg was evaluated in an experimental rat model, using diazepam (5 mg/kg) as positive control. Anxiolytic activity was performed using elevated plus maze method. Phytochemical screening revealed that M. scandens extracts contain carbohydrates, flavonoids, saponins, glycosides, tannins, terpenoids, phenols and phytosterols. The aqueous extract at a dose of 500 mg/kg significantly increased seizure latency (P=0.0023), while the ethanolic extract did not have a significant effect on seizure latency. Both extracts significantly reduced the seizure severity (P= 0.0155), and provided up to 100% protection against PTZ induced death at 1000 mg/kg. Both extracts had no significant effect on the duration of PTZ induced seizures. Both extracts were found to increase the number of entries and the time spent in the open arms of the maze at a dose of 250 mg/kg, indicating anxiolytic activity, which was not seen at higher doses (500 and 1000 mg/kg). The total numbers of entries into the closed arm were significantly reduced at 500 and 1000 mg/kg oral doses of both extracts, indicating a reduction in locomotor activity of the rats. The results obtained in this study suggest that both the aqueous and ethanolic extracts of M. scandens possess anticonvulsant and anxiolytic activities in a rat model.
... Nirvisha [46][47][48][49][50][51] 26 Emblica officinalis Gaertn. Amalaki [52,53] 27 Ficus carica L. Phalgu [54] 28 Ficus religiosa L. Ashwattha [55,56] 29 Glycyrrhiza glabra L. Yashtimadhu [57][58][59][60][61] 30 Hibiscus rosa-sinensis L. Japakusuma [18] 31 Hyoscyamus niger L. Parasika yavani [62] 32 Indigofera tinctoria L. Neelini [63] 33 Marsilea quadrifolia L. Sunishanna [64,65] 34 Mimosa pudica L. Lajjalu [66] 35 Moringa oleifera Lam. Shigru [67,68] 36 Myristica fragrans Houtt. ...
The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy".
Copyright © 2015 Elsevier Inc. All rights reserved.
... 2009), and to cure diarrhoea and dysentery (Sen & Behera, 2008). Experimental studies showed that extracts of leaf and stem of M. quadrifolia have significant anti-epileptic efficacy (Sahu et al., 2012), extracts of leaf possess vast potential as medicinal drug in breast cancer treatment (Uma & Pravin, 2013), Alzheimer's disease (Ashwini et al., 2012), and antimicrobial and antifungal activity against human pathogenic microorganisms (Gopalakrishnan & Udayakumar, 2014). ...
... The current pharmacological intervention remains insufficient for control and complete prevention of epileptic seizure. Although these drugs control or reduce epileptic seizure, their usage is associated with undesirable side effects ranging from gingival hyperplasia, hepatotoxicity and megaloblastic anemia (Surajit Sahu et al., 2012;Guan et al., 2009;Gupta and Malhotra, 2000;Schimtz, 2006). Several new drugs have been approved or are in process of approval, but their efficacy does not appear to be superior to that of available drugs (Perucca, 1996). ...
Many naturally occurring compounds are known for their therapeutic uses in epilepsy disorders. Extracts of Eclipta alba and Pistacia integerrima are known for their antiepileptic activities. Phytochemical investigations of these plants have shown presence of luteolin, α-pinene, β-pinene and terpinen-4-ol constituents, respectively. However, the anticonvulsant activities of these constituents and their mechanism of anticonvulsant actions are not known. The present work deals with proposing the possible receptor involved in binding of these phytoconstituents. To find their possible binding modes, we explore the molecular-level interactions using in silico molecular docking studies using validated docking protocols on homology model of sodium channels. Further, we validate this hypothesis by pharmacological evaluation in maximal electroshock animal model.
... 30 min after i.p. injection of Diazpam and 60 min after oral administration of extracts, 60 mg/kg PTZ was injected subcutaneously. The anticonvulsant properties of different extracts were accessed by its ability to delay the onset of myoclonic spasms and clonic convulsions.17,18 ...
Aim
The aim of present work was to study the pharmacognostic standardization, physicochemical, phytochemical and pharmacological evaluation of the stem of Bacopa monnieri L.
Method
Standard method was followed for pharmacognostic, physicochemical, and phytochemical study. For quantitative analysis, HPTLC technique was employed. Maximal electroconvulsive shock (MES) and pentylenetetrazole (PTZ) method was used for anticonvulsant evaluation.
Result
Microscopic study of the stem showed presence of epidermis and cortex having large intercellular spaces. The oval shaped starch grains were present in cells of cortex and endodermis. Total ash (5.98%), water-soluble ash (4.91%), acid-insoluble ash (3.96%), water soluble extractive (15.31%) and ethanol soluble extractive (6.74%) values were evaluated for physicochemical evaluations. Quantitative estimation of Bacoside A (marker compound) by HPTLC technique was performed. The linearity (100–600 ng), the % recovery (97.81% w/w) were estimated. The Bacoside A in the alcoholic extract was found to be higher than that of the other extracts. The proposed HPTLC method was found to be simple and accurate. The anticonvulsant activities of all the extracts were evaluated by MES and PTZ models in mice.
Conclusion
The least anticonvulsant potential was recorded for acetone extract in dose of 100 mg/kg and maximum anticonvulsant action was recorded for ethanolic extract in dose of 300 mg/kg.
... Neurological disorders such as epilepsy, Parkinson disease, Alzheimer disease, psychiatric disorders and depressive illnesses have been studied extensively [3,4,5].The link between herbs and the management of these diseases have been investigated through researches using various in vitro and in vivo models. Anticonvulsant activity of plants have been studied by a lot of researchers, example includes Casimiroa edulis [6], Rhus chirindensis stem bark [7], Cotyledon orbiculata leaf extract [8] , Marsilea quadrifolia [9], aqueous root extract of Ficus religiosa [10] and a lot of other studies which we cannot mention. The present study aims to investigate the preliminary anticonvulsant activity of Evolvulus alsinoides by using the Maximal electroshock seizure and the Pentylenetetrazole induced seizure models. ...
The purpose of this research work is to study the anticonvulsant activity of Evolvulus aisinoides Linn (convolvulacea) used in traditional medicine for the treatment of neurodegenerative diseases, amnesia, mental illness and epilepsy. In this study, the anticonvulsant activity of the crude methanolic extract was investigated at doses of 50, 100, 200 and 400 mg/kg using the Pentylenetetrazole (PTZ) induced seizure (chemically induced seizure) and maximal electroshock seizure (electrically induced seizure) models in mice. The sedative hypnotic effect was also studied using the Diazepam induce sleep model. The onset of diazepam induced sleep was decreased dose dependently; there was a marked increase in duration of sleep to 4-7 times the duration of sleep in the control group.. The extract at doses of 100-400 significantly increased the latency of PTZ induced seizure; there was a 100% protection against seizure at the highest dose of 400mg/kg. In the MEST test a dose dependent decrease in the duration of seizure was also observed with all the doses administered.400mg/kg of the extract and 30mg/kg Diazepam shows the highest activity in this test. These findings suggest that the methanol extract of the plant contains bioactive principles that may be beneficial in the treatment of epilepsy. INTRODUCTION Traditional, alternative or herbal medicine refers to medical/medication practices other than orthodox medicine/medical practice. The name as called in different places symbolizes safety in contrast to synthetic or orthodox medicines [1].The use of herbal medicine as an adjunct or substitute to orthodox medicine has gained much popularity worldwide. The WHO reported that about 80% of people in the third world countries depend wholly or partly on herbal medicines for their medications [2]. Most researchers have tried to provide a scientific link/basis to explain the traditional claims of efficacy of most herbs by using in vitro and in vivo experimental models. Neurological disorders such as epilepsy, Parkinson disease, Alzheimer disease, psychiatric disorders and depressive illnesses have been studied extensively [3,4,5].The link between herbs and the management of these diseases have been investigated through researches using various in vitro and in vivo models. Anticonvulsant activity of plants have been studied by a lot of researchers, example includes Casimiroa edulis [6], Rhus chirindensis stem bark [7], Cotyledon orbiculata leaf extract [8] , Marsilea quadrifolia [9], aqueous root extract of Ficus religiosa [10] and a lot of other studies which we cannot mention. The present
... Neurological disorders such as epilepsy, Parkinson disease, Alzheimer disease, psychiatric disorders and depressive illnesses have been studied extensively [3,4,5].The link between herbs and the management of these diseases have been investigated through researches using various in vitro and in vivo models. Anticonvulsant activity of plants have been studied by a lot of researchers, example includes Casimiroa edulis [6], Rhus chirindensis stem bark [7], Cotyledon orbiculata leaf extract [8] , Marsilea quadrifolia [9], aqueous root extract of Ficus religiosa [10] and a lot of other studies which we cannot mention. The present study aims to investigate the preliminary anticonvulsant activity of Evolvulus alsinoides by using the Maximal electroshock seizure and the Pentylenetetrazole induced seizure models. ...
The purpose of this research work is to study the anticonvulsant activity of Evolvulus aisinoides Linn (convolvulacea) used in traditional medicine for the treatment of neurodegenerative diseases, amnesia, mental illness and epilepsy. In this study, the anticonvulsant activity of the crude methanolic extract was investigated at doses of 50, 100, 200 and 400 mg/kg using the Pentylenetetrazole (PTZ) induced seizure (chemically induced seizure) and maximal electroshock seizure (electrically induced seizure) models in mice. The sedative hypnotic effect was also studied using the Diazepam induce sleep model. The onset of diazepam induced sleep was decreased dose dependently; there was a marked increase in duration of sleep to 4-7 times the duration of sleep in the control group.. The extract at doses of 100-400 significantly increased the latency of PTZ induced seizure; there was a 100% protection against seizure at the highest dose of 400mg/kg. In the MEST test a dose dependent decrease in the duration of seizure was also observed with all the doses administered.400mg/kg of the extract and 30mg/kg Diazepam shows the highest activity in this test. These findings suggest that the methanol extract of the plant contains bioactive principles that may be beneficial in the treatment of epilepsy. INTRODUCTION Traditional, alternative or herbal medicine refers to medical/medication practices other than orthodox medicine/medical practice. The name as called in different places symbolizes safety in contrast to synthetic or orthodox medicines [1].The use of herbal medicine as an adjunct or substitute to orthodox medicine has gained much popularity worldwide. The WHO reported that about 80% of people in the third world countries depend wholly or partly on herbal medicines for their medications [2]. Most researchers have tried to provide a scientific link/basis to explain the traditional claims of efficacy of most herbs by using in vitro and in vivo experimental models. Neurological disorders such as epilepsy, Parkinson disease, Alzheimer disease, psychiatric disorders and depressive illnesses have been studied extensively [3,4,5].The link between herbs and the management of these diseases have been investigated through researches using various in vitro and in vivo models. Anticonvulsant activity of plants have been studied by a lot of researchers, example includes Casimiroa edulis [6], Rhus chirindensis stem bark [7], Cotyledon orbiculata leaf extract [8] , Marsilea quadrifolia [9], aqueous root extract of Ficus religiosa [10] and a lot of other studies which we cannot mention. The present
... Further studies are warranted to elucidate the exact compound responsible for these actions. Water extract of M. quadrifolia is reported to have an anti-convulsive effect in rats [36]. The CNS depressant and sedative effects of MQ were also documented earlier [12]. ...
Objective:
To study the anti-epileptic effects of methanolic extract of Marsilea quadrifolia Linn. (MQ) in maximal electroshock (MES) and pentylenetetrazole (PTZ) induced rat models of epilepsy.
Method:
A total of 84 adult male Wistar rats were used. An acute oral toxicity study was conducted on 36 rats and the remaining were used for other experiments. Each model had 24 rats which were allotted into four groups (n = 6). Group I (Control) received 1% carboxymethyl cellulose solution, Group II (Positive control) received phenytoin 300 mg kg(-1) b.w. in the MES model; sodium valproate 200 mg kg(-1) b.w. in the PTZ model, Group III (MQ) received 400 mg kg(-1) b.w. MQ extract and Group IV (MQ) received 600 mg kg(-1) b.w. MQ extract. Hind limb extension (HLE) time and recovery time were noted in the MES model. Latency for myoclonic jerk, seizures and EEG was recorded in the PTZ model.
Results:
When compared to control, the phenytoin received group did not show HLE. In MQ pre-treated groups only 50% of rats showed HLE. Sodium valproate and various doses of MQ significantly increased the latency for onset of clonus and seizures. PTZ-induced EEG alterations were significantly attenuated by MQ administration and this was comparable to that of the sodium valproate effect.
Conclusion:
Marsilea quadrifolia Linn. showed significant anti-epileptic efficacy against various epilepsy models.
Relevance: More than 70 million people suffer epilepsy worldwide. Low availability of anti-epileptic drugs, side-effects and drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a poorly developed health system. Herbal medicine is frequently used for this neurological condition. Objectives: The main objective was to provide a detailed analysis of Herbal Medicine used for neurological conditions related with epilepsy in Asia, Africa and Latin America. More broadly, this study aims to highlight species with assessed efficacy (cross-cultural use, pharmacological effects on models of epileptic seizures) and safety (toxicological data in laboratory) information, in order to point out species of interest for further studies. A critical assessment of models used in pharmacological evaluations was done. Materials and methods: The systematic search for Herbal Medicine treatments for epilepsy was performed considering all the articles published until February 2017 through three scientific databases. It was made with MeSH terms and free text defining the epilepsy seizures and plant species. We included studies carried out in Asia, Africa and Latin America. All articles reporting the use of Herbal Medicine to treat epilepsy seizures and/or their pharmacological evaluation were retained for further analysis. Results: The search yielded 1886 articles, from 30 countries. Hundred and six articles published between 1982 and 2017 were included, corresponding to a total of 497 use reports for 351 plant species belonging to 106 families. Three hundred and seventy seven use reports corresponding to 264 species in ethnopharmacological surveys and 120 evaluation reports corresponding to 107 species were noted. Twenty-nine reports, for 29 species, combined both ethnopharmacological and pharmacological evaluation. Fifty eight studies originated from Africa, 35 studies from Asia and 18 from Latin America. Highest use report was noted for rhizomes of Acorus calamus L. (12 use report in 1 country) and leaves of Bacopa monnieri (L.) Wettst. (8 use report in 2 countries). Therefore these species display the highest use convergence. Regarding pharmacological evaluation most studied species were: Leonotis leonurus (L.) R.Br. (4 evaluation reports in 1 country), Uncaria rhynchophylla (Miq.) Miq. ex Havil. (3 evaluation reports in 2 countries) and Calotropis gigantea (L.) Dryand. (3 evaluation reports in 1 country). In vivo models of chronic epilepsy were more relevant than in vitro models or chemical models inducing acute seizures for pharmacological assessment. Conclusion: Species with the highest use report were not those with pharmacological evaluation. It will be pertinent to assess the pharmacological effects and safety of medicinal plants used mostly by traditional healers on predictive models of seizures.
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. © 2016 Journal of Pharmaceutical Negative Results | Published by Wolters Kluwer - Medknow.
The present study was designed to evaluate the antistress effect of Marsilea quadrifolia ethanolic extract in stress induced behavioural and physiological alteration in the mice. Anti-stress activity was evaluated using physical stress models viz. swimming endurance and post swimming motor function test, anoxic tolerance test and restraint stress test. Swiss albino mice (18-25 g) divided into four groups of six animals each were used for the study. Control group received CMC as vehicle and standard group received Withania somnifera (100 mg/kg) while Marsilea quadrifolia ethanolic extract (200 and 400 mg/kg) were administered orally for seven days. Change in immobility time in swim endurance and first clonic convulsion in anoxic tolerance test and stress-induced behavioral and biochemical alterations in immobilization stress was recorded as parameters. Marsilea quadrifolia ethanolic extracts significantly reduces the immobility timing along with increases the swimming endurance time, post motor function and clonic convulsion timing in anoxic tolerance test as compared to control group and significantly reversed the behavioral and biochemical alterations in restraint stress. © 2014, Journal of Chemical and Pharmaceutical Research. All rights reserved.
The electroencephalogram (EEG) is often applied to diagnose the diseases of the nervous system because of its advantages of high time resolution, clear observation to the dynamic changes for the brain activity, and the completely non-invasive detection. To explore somatosensory evoked potential (SEP) changes and functional recovery of the cerebral cortex following cerebral ischemia, 25 Sprague Dawley male rats have been divided into 5 groups, which include control group and four ischemia groups, 4 h group, 24 h group, 48 h group and 1 w group. The rat model of cerebral ischemia has been established by middle cerebral artery occlusion (MCAO) in the left hemisphere. SEP of left cortex was detected by electrically stimulating the right median nerve of rat paw. The EEG in resting state was analyzed by spectral technology. The result shows that, after 4 hours of MCAO the latency of SEP has been significantly prolonged ((16.0 ± 1.1) ms vs (33.7 ± 1.3) ms, P < 0.01), and the amplitude is decreased ((197.2 ± 13.0) μV vs (25.1 ± 2.0) μV, P < 0. 01). The energy of θ wave, α wave, β wave, γ wave are significantly smaller. θ wave: (139 367.86 ± 178.66) μV 2 vs (2.22 ± 0.40) μV2, P < 0.01; α wave: (5 389.33 ± 25.55) μV2 w(0.23 ± 0.01) μV2,P < 0.01; β wave: (79.11 ± 4.16) μV 2 vs(0.01 ± 0.01) μV2, P < 0.01; γ wave: (0.30 ± 0.12) μV2 vs(0.00 ± 0.00) μV 2, P < 0.01. With the extension of time after operation, the difference of these characteristics between control group and ischemia group has been reduced gradually (P < 0.01). However, these characteristics cannot reach the normal. This indicates that SEP can be used to evaluate the function of cerebral cortex in rats with cerebral ischemia in a certain extent.
Objective: In this study, the effects of ethanolic extract of Alstonia scholaris (EAS) were evaluated on epilepsy models. Methods: Pentylenetetrazole (PTZ), pilocarpine, and maximal electroshock (MES)-induced convulsions in mice were recorded. EAS (100, 200, and 300 mg/kg, p.o.) protected of mice against PTZ, pilocarpine, and MES-induced seizures, respectively. Results: In MES-induced seizures, the results revealed that EAS decreased the duration of the tonic hindlimb extension and percent mortality. In addition, these doses of EAS increased the latency for the development of convulsions and reduced mortality in mice against PTZ and pilocarpine-induced convulsions. Conclusion: The ethanolic extract of bark A. scholaris exhibited anticonvulsant potential in various animal models. © 2015, Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.
Marsilea quadrifolia is an edible aquatic medicinal plant used as a traditional health food in Asia. Four new polyphenols including kaempferol 3-O-(2″-O-E-caffeoyl)-β-d-glucopyranoside (1), kaempferol 3-O-(3″-O-E-caffeoyl)-α-l-arabinopyranoside (3), 4-methy-3'-hydroxypsilotinin (4) and (±)-(E)-4b-methoxy-3b,5b-dihydroxyscirpusin A (18) together with 14 known ones (2, 5-17) were isolated from the ethanol extract of M. quadrifolia. Structures of the new compounds were elucidated by extensive spectroscopic analyses. In DPPH and oxygen radical absorbance capacity antioxidant assays, some compounds showed stronger antioxidant activities and quercetin (9) was the most potent antioxidant in both assays. In a restraint-induced oxidative stress model in mice, quercetin significantly attenuated the increase in plasma ALT and AST levels as well as liver MDA content of restrained mice. Liver SOD activity was also significantly increased by quercetin, indicating a significant in vivo antioxidant activity. As a rich source of polyphenols with strong antioxidant activities, M. quadrifolia may be developed to a product for relieving oxidative stress.
The main aim of this study was to find out the antibacterial, antioxidant and cytotoxic activity of petroleum ether, chloroform and ethyl acetate extracts of Marsilea quadrifolia (Family: Marsileaceae). For antibacterial test, Disc diffusion technique was used against 5 Gram positive and 11 Gram negative human pathogenic bacteria. The range of zone of inhibition of chloroform and ethyl acetate extracts was 9 to 20 mm. The petroleum ether extract did not show any zone of inhibition against any tested pathogenic bacteria. The Brine shrimp lethality bioassay method was used to determine the cytotoxicity activities and Vincristin sulphate was used as a positive control. The LC50 values of standard Vincristin sulphate, petroleum ether, chloroform and ethyl acetate extracts were 6.628μg/ml, 9.543μg/ml 7.820 μg/ml, and 8.589µg/ml respectively. All the fractions showed potent antioxidant activity, of which the ethyl acetate fraction demonstrated the strongest antioxidant activity with the IC50 value of 50.1053 μg/ml.
We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Ca2+ and Na+ levels continued to decrease except when CBZ was used, which preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ.
During acute febrile diseases mild disturbances of water and electrolyte balance occur frequently. It has been suggested that changes in electrolyte balance, in particular hyponatraemia, might predispose a child to convulsions during febrile illness; however, the changes of electrolytes in the CSF are not known.
We have studied the effects of fever and convulsions on water and electrolyte balance in CSF and serum by measuring osmolality and electrolyte concentrations in children. The febrile population consisted of 60 children, 36 of whom had seizures during fever. Twenty-one children without convulsions and nine children with epileptic symptoms were nonfebrile controls. We noticed that CSF is subject to changes in osmolality and electrolyte concentration during fever, while convulsions do not exhibit such changes. CSF osmolality and sodium concentrations were lower in febrile children than in nonfebrile controls. The osmolality in febrile children with convulsions was 3.8% (P<0.01) and without seizures 3.5% (P<0.01) lower than in nonfebrile nonconvulsive children. The changes in CSF sodium concentration, and to a lesser extent potasium and chloride concentrations, paralleled those of CSF osmolality. A positive correlation was observed between the CSF and serum osmolatities (r=0.73,P<0.0001), and sodium concentrations (r=0.63,P<0.0001). A negative correlation between the body temperature and both CSF osmolality (r=−0.66,P<0.0001) and sodium concentration (r=−0.59,P<0.0001) exhibits also the important regulative role of increased body tmeperature.
Conclusion
Fever is an important factor for disturbances in fluid and electrolyte balance. The alterations in CSF osmolality and sodium concentration do not, however, give an unambiguous explanation for the susceptibility to simple febrile seizures.
An animal model is described which allows for differentiation of 8 common drug categories (antidepresssives, anticonvulsive, analgesic, neuroleptic, stimulant, narcotic, sedative and hallucinogenic drugs) by recording field potentials from stereotactically implanted electrodes and wireless transmission of the data. Four to five representatives of each drug category have been looked at in terms of changes of frequency content with respect to 6 different frequency ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Basically all drugs within one category show a very similar pattern of changes providing a disease specific "fingerprint" of electrical activity. Discriminant analysis provides the statistical fundament for classification of single drugs into disease specific clusters. The data suggest that this type of analysis of the electrical activity of the brain not only allows for classification of unknown compounds but also can accelerate drug development to a major degree. Finally the recognition of new indications of already launched drugs not only becomes feasible but has resulted in filing of new indication patents.
A drug interaction refers to an event in which the usual pharmacological effect of a drug is modified by other factors, most frequently additional drugs. When two drugs are administered simultaneously, or within a short time of each other, an interaction can occur that may increase or decrease the intended magnitude or duration of the effect of one or both drugs. Drugs may interact on a pharmaceutical, pharmacokinetic or pharmacodynamic basis. Pharmacodynamic interactions arise when the alteration of the effects occurs at the site of action.
This is a wide field where not only interactions between different drugs are considered but also drug and metabolites (midazolam/α-hydroxy-midazolam), enantiomers (ketamine), as well as phenomena such as tolerance (nor-diazepam) and sensitization (diazepam). Pharmacodynamic interactions can result in antagonism or synergism and can originate at a receptor level (antagonism, partial agonism, down-regulation, up-regulation), at an intraneuronal level (transduction, uptake), or at an interneuronal level (physiological pathways).
Alternatively, psychotropic drug interactions assessed through quantitative pharmaco-EEG can be viewed according to the broad underlying objective of the study: safety-oriented (ketoprofen/theophylline, lorazepam/-diphenhydramine, granisetron/haloperidol), strictly pharmacologically-oriented (benzodiazepine receptors), or broadly neuro-physiologically-oriented (diazepam/buspirone). Methodological issues are stressed, particularly drug plasma concentrations, dose-response relationships and time-course of effects (fluoxetine/buspirone), and unsolved questions are addressed (yohimbine/caffeine, hydroxizyne/alcohol).
The hydro alcoholic extract of the entire plant Marsilea quadrifolia (HEMQ) was evaluated for different psychopharmacological actions such as behaviour, exploratory behaviour, muscle relaxant activity and phenobarbitone induced sleeping time. The extract was found to cause reduction in spontaneous activity, decrease in exploratory behavioural pattern by swimming and pole climbing test., reduction in the muscle relaxant by traction test. In addition, the extract significantly potentiated the phenobarbitone-induced sleeping time. Preliminary tests indicate that the hydro alcoholic extract of Marsilea quadrifolia in doses of 200-400 mg/kg has significant psychopharmacological activity.
Herbs and dietary supplements enjoy widespread use in the treatment of epilepsy although supportive data yielding efficacy and safety are lacking. Ten specific products, American hellebore, betony, blue cohosh, kava, mistletoe, mugwort, pipsissiwa, skullcap, valerian, and melatonin, have either multiple-cited recommendations for use in epilepsy or a rationale for antiepileptic action and are discussed in detail. These items paradoxically often have a proconvulsant effect in addition to potentially serious adverse effects. Herb-drug interactions also occur at the level of the P450 hepatic enzyme system of drug catabolism and the P-glycoprotein transport system regulating the entry of exogenous compounds into the vasculature or blood-brain barrier. Thus, significant pharmacokinetic interactions may occur, in addition to pharmacodynamic interactions and proconvulsant effects of alternative medications themselves. Patients should be inquired as to the nature of any alternative medicine products they are using, with the view that these products may be reasonable if traditional antiepileptic drug therapy is continued, potential adverse effects of the alternative agents are monitored, and the alternative and traditional agents do not conflict.
Maesilea quadrifolia Linn. (Marsileaceae) is a leafy vegetable well known in India. The current study aims to explore the phytochemical profile of M. quadrifolia and investigate its anti-cholinesterase potential. The methanol extract of the plant was subjected to qualitative and quantitative phytochemical screening (total alkaloidal content, saponin content and phenol content) and its anti-cholinesterase potential was tested by TLC bioautography and other screening methods using acytylcholinesterase (AChE) and butyrylcholinesterase (BChE). The study revealed that the extract contains various classes of phytoconstituents including steroids, saponins, alkaloids and other polyphenols. Total alkaloid, phenolic and saponin contents were found to be 19.3 mg g⁻¹ and 158.5 ± 1.02 mg g⁻¹ as gallic acid equivalents and 2.63 mg g⁻¹ of the extract, respectively. The TLC bioautography method exhibited the inhibition of both enzymes. In a microtiter plate assay, the IC₅₀ values of the extract for AChE and BChE were found to be 51.89 ± 0.24 µg mL⁻¹ and 109.43 ± 2.82 µg mL⁻¹, respectively. These findings suggest that M. quadrifolia is a potential lead as an AChE and BChE inhibitor, which may be useful in the management of Alzheimer's disease.
Khat is a plant with psychostimulant properties whose parts, mainly leaves and twigs, are chewed for its euphoriant effects. Khat use and ethanol abuse are increasingly becoming global health concerns especially among many disadvantaged social groups. The present studies were undertaken to investigate seizure susceptibility and responses following chronic co-administration of khat and ethanol.
Juvenile male Sprague-Dawley (SD) rats were administered khat, ethanol or combined khat and ethanol twice daily for 28 days by gavage. Khat-treated animals received 2 g/kg or 4 g/kg body weight continuously for the study period. Ethanol-treated animals received 20% ethanol at a dose of 4 g/kg body weight. The convulsant, pentylenetetrazol (PTZ), was administered intraperitoneally at a dose of 40 mg/kg body weight. Seizure responses were recorded.
Twice-daily dosing of khat did not produce inhibition of weight gain. Khat alone, combined khat and 20% ethanol, but not 20% ethanol alone, significantly reduced the latency to seize. Khat treatment at 2 g/kg but not 4 g/kg body weight also significantly increased the duration of seizures. Conversely, combined khat and ethanol reduced the duration of seizures compared to controls. Ethanol alone reduced the seizure severity while khat alone, and combined khat and ethanol, produced close to the maximum seizure severity.
These data suggest that combined moderate to high dose khat and ethanol co-dependence produce a greater deleterious CNS effect than either drug alone. Future studies will address neurochemical effects, in addition to neuroadaptations, resulting from coabuse of these drugs.
To determine the prevalence of herb and dietary supplement use and to provide a comprehensive analysis of factors influencing the use of these products in patients with epilepsy.
We performed a cross-sectional study using self-administered questionnaires in a selected group of patients who were receiving care at a tertiary epilepsy center. Logistic regression was used to measure the association between the demographic variables and herb and dietary supplement use. In addition, we performed a MEDLINE search for each of the herb and dietary products used by our patients to determine the effect of these products on seizures and on their potential for interactions with other drugs metabolized by the liver.
One hundred eighty-seven patients completed the survey. Fifty-six percent of this group of patients with epilepsy used herbs and dietary supplements at the time of the survey. A considerable portion (71%) of these patients reported the use of these products to their physician, and most of them relied on their physicians as the primary source of information. Most of the patients used dietary supplement for health promotion rather than to specifically benefit their epilepsy condition. Approximately one-third of patients used herb or dietary supplements that had the potential to increase seizures (16%) or to interact with hepatically metabolized drugs (19%). The most powerful independent predictors of herb and dietary supplement use were partial epilepsy [odds ratio (OR) 3.36; 95% confidence interval (CI) 1.27-8.88] and Caucasian race (OR 3.55; 95% CI 1.11-11.34).
Patients with epilepsy commonly used dietary supplements along with their antiepileptic medications. The majority of these patients used herb and dietary supplements for health promotion rather than because of dissatisfaction with conventional treatment. It is important that physicians involved in the care of patients with epilepsy routinely inquire about the use of dietary supplements and that they make use of reliable resources to assess the safety of these products with regard to modification of seizure risk and the potential for interactions with antiepileptic drugs.
In order to be able to test single constituents of herbal plant extracts with respect to possible clinical usefulness, the model of local field potential analysis leading to the so-called electropharmacogram has been successfully used in rats to classify the effects of theanine and theogallin in the past. The present investigation aims at the prediction of efficacy and possible mechanisms of action of rutin and quercetin. Adult rats (day-night converted) were instrumented with four bipolar concentric electrodes into the frontal cortex, hippocampus, striatum and reticular formation. Field potentials were recorded during a pre-drug reference period of 45 min followed by oral administration of the particular test compound and 4h recording thereafter. Data were transmitted wirelessly to the computer for spectral frequency analysis. Rutin (5-80 mg/kg) as well as quercetin (5-40 mg/kg orally) produced similar electropharmacograms with dose dependent decreases of spectral alpha2 and beta1 frequencies within all brain areas. Peak effects were reached 4h after administration. The pattern of changes approached that obtained after 2.5mg/kg of moclobemide during the first hour as revealed by discriminant analysis in comparison to a large matrix of other drugs with known clinical indications. Data suggest antidepressant capabilities for rutin and quercetin with inhibition of monoamino oxidase at least as part of the mechanism of action. Both compounds should be tested clinically in patients with symptoms of depression.
Prostaglandin E1-(PGE1-) induced inhibition of pentylenetetrazol (PTZ) convulsions in rats were significantly antagonized after pretreatment with drugs known to reduce brain serotonin activity, but not by pharmacological agents that decrease brain catecholamine activity. PGF2alpha also significantly inhibited PGE1 action. The results suggest that PGE1-induced inhibition of PTZ convulsions is not a direct effect, but an indirect one mediated through increase in brain serotonin activity.
Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in rats. Rats were exposed to one of six graded concentrations (110.6, 162.5, 432, 676, 1558, 2730 ppm) of toluene on different days. It was found that the duration of waking (W) was increased with a decrease in duration of rapid eye movement (REM) sleep even at 110.6 ppm. Duration of nonrapid eye movement (NREM) sleep was decreased with an increase of W and a decrease of REM sleep at 162.5 ppm. Dose-related effects were noted in higher concentrations. The power of delta frequency band was increased with a decrease of theta frequency band power at hr 1 of exposure to 676 ppm during REM sleep recorded from the visual cortex. The power of theta frequency band was also decreased at hr 2 of exposure at 432 ppm. During W and NREM sleep power spectra were not changed significantly. Results indicate that the changes of EEG are a sensitive measure of the effects of toluene on the central nervous system (CNS).
The term epilepsy is collectively designated for a group of chronic central nervous system disorders characterized by spontaneous occurrence of seizures generally associated with the loss of consciousness and body movements (convulsions). The disease has its origin from an early age. Anticonvulsant drugs are used to control the convulsions by inhibiting the discharge and then producing hypnosis. Various synthetic drugs, viz. sodium diphenyl hydantoin (Dialtin) barbiturates, pyrimidon, succinamides, diazepines etc. are used for the treatment. In this paper various medicinal plants and plant components, which are being used as anticonvulsant and antiepileptic, are discussed.
In mice and rats, the influence of controlled variations in the central levels of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) on the convulsive threshold in electro- and pentetrazole seizures was studied. The threshold for maximal electroconvulsions was lowered by treatments depressing the central levels of 5-HT and noradrenaline, by the 5-HT antagonist cyproheptadine, and the α-adrenolytic phentolamine. Treatment with l-DOPA or 5-hydroxytryptophan (5-HTP) raised the threshold. The results point to a significance of 5-HT and noradrenaline for the sensitivity to electroconvulsion. The threshold for the clonic component of the pentetrazole convulsion was depressed by treatments lowering the central level of noradrenaline, and by the β-adrenolytic propranolol; it was elevated by l-DOPA (only in mice). Depletion of 5-HT by p-chlorophenylalanine lowered the threshold only in rats, but it was increased by 5-HTP in both species. Thus, noradrenaline plays a role in the mediation of the clonic pentetrazole convulsion, and 5-HT does so in the rat, whereas its importance remains dubious in the mouse. The threshold for the tonic extensor component of the pentetrazole convulsion (only determined in mice) was lowered by p-chlorophenylalanine and cyproheptadine, and slightly elevated by 5-HTP. There was no indication for a crucial role of noradrenaline or dopamine in this component of the pentetrazole convulsion. The effect of treatments with (+)-amphetamine and (+)-p-chloroamphetamine on the convulsive thresholds point to a predominantly noradrenergic stimulation by the former, and a mixed influence of the latter on the metabolism of central 5-HT and noradrenaline.
Many epileptic patients suffer from cognitive impairments. These impairments may be a consequence of the epileptogenic process and/or antiepileptic medication. Kindling is considered a useful experimental model to investigate drug effects on both the convulsive component of epilepsy and related alterations at the behavioral level. In our experiments, kindling was induced by repeated injections of pentylenetetrazol (PTZ). To test the effect of antiepileptic drugs on kindled seizures and kindling-induced learning deficits we injected ethosuximide, dipropylacetate, and phenobarbital prior to each kindling stimulation or after kindling completion, and tested these animals in a shuttle-box paradigm. Dipropylacetate and phenobarbital suppressed the development of motor seizures and counteracted the learning deficit. Although ethosuximide had a clear effect on kindled seizures, the learning deficit occurred in kindled rats. This suggests that AEDs effects on kindled seizures are not correlated with the elimination of deficits in the field of cognition.
Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the 'atoms of thought'.
During the last decade, several new antiepileptic drugs (AEDs) have been introduced in Europe, the United States, or other parts of the world. Although the antiepileptic efficacy of these drugs is not superior to that of older AEDs, some of the new drugs offer advantages in terms of improved tolerability, ease of use, and reduced interaction potential with other drugs. However, the new AEDs have only a modest impact on patients with refractory epilepsies, so that about one third of patients with epilepsy continue to have seizures with current pharmacotherapies. Thus, there is a continuing need for new medical therapies in epilepsy. During the Workshop on "New Horizons in the Development of Antiepileptic Drugs" (November 28-29, 2001, Philadelphia, PA), one topic dealt with the critical re-evaluation of previous preclinical strategies for the discovery and the development of new AEDs. The discussion of this session, which was chaired by the authors, is summarized in this article. Main issues of the discussion were whether epilepsy is a progressive disease and whether refractory epilepsy is preventable, the use of acute versus chronic animal models in the discovery and development of new AEDs, models for drug-resistant epilepsy, mechanisms of drug resistance, alterations in adverse effect potential of AEDs by epilepsy, and advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy. Overall, it was felt that the current preclinical strategies for the discovery and development of new AEDs have to be redefined in order to identify agents that are clearly superior to current medications.
Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating neuronal pH and, hence, modulate bioelectric and seizure activity. In this study, we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizures in mice. Further, the effect of amiloride on mood, memory, grip strength, and rotarod performance was also evaluated. The forced swimming test (FST) and spontaneous alternation behavior (SAB) models were employed to assess the effects on mood and memory, respectively. Amiloride produced a dose-dependent increase in seizure threshold in both rodent models of epilepsy. It was observed that amiloride reduced behavioral depression in the FST in mice. In addition, it resulted in memory improvement in the SAB model. Amiloride did not affect grip strength and rotarod performance, suggesting it is devoid of behavioral impairment. The results indicate the potential antiseizure activity of amiloride along with additional neurological advantages.
The effects of tianeptine and fluoxetine on pentylenetetrazole (PTZ)-induced seizures in rats were investigated. Female Wistar rats (172-278 g) were used in the study. Tianeptine (1.25, 2.5, 5, 10 and 20 mg/kg) and fluoxetine (2.5, 5, 10 and 20 mg/kg) or saline were injected to rats intraperitoneally 30 min before PTZ (50 mg/kg) injections. Immediately after PTZ administrations, latency and intensity of the PTZ-induced seizures was recorded and scored, respectively. Fluoxetine (2.5-20 mg/kg) did not produce any significant difference in latency and intensity of the PTZ-induced seizures. Although tianeptine (1.25-20 mg/kg) also did not affect the latency time, it produced significant attenuations in the intensity of the seizures. Tianeptine did not cause any significant change in the locomotor activity of the rats. The results of this preliminary study suggest that tianeptine but not fluoxetine has some inhibitory effects on PTZ-induced seizures in rats.
In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT(1A), 5-HT(2C), 5-HT(3) and 5-HT(7) receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT(1A) or 5-HT(2C) receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT(1A) receptors and depolarization of GABAergic neurons by 5-HT(2C) receptors as well as antagonists of 5-HT(3) and 5-HT(7) receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies.
The use of complementary and alternative medicine is on the rise, including among patients with epilepsy. Herbal medicine, one of the most popular forms of CAM, is considered to be both safe and effective by most consumers. Yet many herbs may increase the risk for seizures, through intrinsic proconvulsant properties or contamination by heavy metals, as well as via effects on the cytochrome P450 enzymes and P-glycoproteins, altering antiepileptic drug (AED) disposition. Herb-drug interactions may be difficult to predict, especially since the quality and quantity of active ingredients are often unknown. Since most patients do not inform their physicians that they are taking herbal medicines, health care professionals must initiate a dialogue in order to prevent complications with the combined regimen. At the same time, further research is required regarding the effect of herbs on seizure activity and interactions with AED treatment.
Marsilea minuta Linn. (Marsileaceae) has been referred in Indian traditional medicine system (Ayurveda) for the treatment of insomnia and other mental disorders. Marsiline isolated from Marsilea minuta was reported to have sedative and anticonvulsant property. The ethanol extract of Marsilea minuta was standardised for marsiline (1.15%, w/w) and studied for its antidepressant activity.
Antidepressant activity was studied using forced swimming test (FST), tail suspension test (TST), learned helplessness test (LHT) and 5-hydroxytryptophan (5-HTP) induced head twitches response in rodents. Standardised extract of Marsilea minuta in doses of 100, 200 and 400 mg/kg/day were administered orally for three consecutive days and evaluated on day 3, 1h after the last dose treatment. Imipramine (15 mg/kg/day, i.p.) was used as the standard drug. Neurochemical mechanism of antidepressant activity was elucidated by using radioligand receptor binding assays for 5-HT2A and benzodiazepine receptors in rat frontal cortex.
Immobility time in FST and TST was significantly (P<0.05) reduced by ethanol extract of Marsilea minuta treated animals. A decrease in number of escape failures in LHT was also observed in Marsilea minuta treated rats. Head twitch response induced by 5-HTP was significantly attenuated by Marsilea minuta (400 mg/kg, p.o.) and imipramine showing the involvement of serotonergic system. This effect was corroborated with radioligand receptor binding study where Marsilea minuta (400 mg/kg, p.o.) significantly (P<0.05) down regulated 5-HT2A receptor in frontal cortex, whereas, no marked effect was observed for benzodiazepine receptor.
The antidepressant effect exhibited by Marsilea minuta extract may be due to its effect on 5-HT2A density in rat frontal cortex.
Medicinal Plants of India Indian Council of Medical Research
- G V Satyavati
- A K Gupta
- N Tandon
Satyavati, G.V., Gupta, A.K., Tandon, N., 1987. Medicinal Plants of India: Vol. 2. Indian Council of Medical Research, New Delhi, p. 222. Sivarajan, V.V., Balachandran, I., 1994. Ayurvedic Drugs and Their Plant Sources.
- M W Nsour
- C B S Lau
- I C K Wong
Nsour, M.W., Lau, C.B.S., Wong, I.C.K., 2000. Review on phytotherapy in epilepsy.
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