Plants with anticonvulsant properties: a review

Jullyana QUINTANS

Seizures are resistant to treatment with currently available anticonvulsant drugs in about 1 out of 3 patients with epilepsy. Thus, there is a need for new, more effective anticonvulsant drugs for intractable epilepsy. However, nature is a rich source of biological and chemical diversity and a number of plants in the world have been used in traditional medicine remedies, i.e., anticonvulsant, anxiolytic, analgesic, antidepressant. This work constitutes a literature review on medicinal plants showing anticonvulsant properties. The review refers to 16 Brazilian plants and a total 355 species, their families, geographical distribution, the utilized parts, method and references. Some aspects of research on medicinal plants and a brief review of the most common animal models to discover antiepileptic drugs are discussed. For this purpose over 170 references were consulted.

Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 18 (Supl.): 798-819, Dez. 2008 Received 1 October 2008; 5 November 2008 Revisão Plants with anticonvulsant properties - a review Lucindo J. Quintans Júnior,*,1 Jackson R.G.S. Almeida,2 Julianeli T. Lima,2 Xirley P. Nunes,2 Jullyana S. Siqueira,1 Leandra Eugênia Gomes de Oliveira,3 Reinaldo N. Almeida,3 Petrônio F. de Athayde-Filho,3 José M. Barbosa-Filho3 1 Departamento de Fisiologia, Universidade Federal de Sergipe, Campus Universitário “Prof. Aloísio de Campos”, 49100-000 São Cristóvão-SE, Brazil, 2 Laboratório de Pesquisa do Vale do São Francisco, Universidade Federal do Vale do São Francisco, Caixa Postal 252, 56306-410 Petrolina-PE, Brazil, 3 Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Caixa Postal 5009, 58051-970 João Pessoa-PB, Brazil RESUMO: “Uma revisão de plantas com propriedades anticonvulsivantes”. Cerca de um terço dos pacientes epilépticos não conseguem ter um tratamento adequado com as drogas anticonvulsivantes atuais. Nesse sentido, as plantas medicinais surgem como uma fonte promissora de novas moléculas químicas com propriedades biológicas apreciáveis. Muitas plantas ou produtos de origem naturais têm sido propostos para o tratamento de várias patologias, tais como: epilepsia, diabetes, ansiedade, depressão, dentre outras. O presente trabalho realizou um extenso levantamento na literatura especializada de plantas medicinais com propriedades anticonvulsivantes. Um total de 355 espécies vegetais foi identificado, sendo 16 plantas encontradas na flora brasileira, com indicação para o tratamento de quadros convulsivos. Características como nome da espécie, família, partes utilizadas, país do estudo e /ou publicação, métodos e referências foram sumarizados. Além disso, os principais apectos dos modelos animais mais utilizados no estudo de plantas/substâncias com propriedades anticonvulsivantes foram revisados. Mais de 170 referências foram consultadas. Unitermos: Plantas medicinais, Produtos naturais, convulsão, atividade anticonvulsivante, modelos animais, revisão. ABSTRACT: Seizures are resistant to treatment with currently available anticonvulsant drugs in about 1 out of 3 patients with epilepsy. Thus, there is a need for new, more effective anticonvulsant drugs for intractable epilepsy. However, nature is a rich source of biological and chemical diversity and a number of plants in the world have been used in traditional medicine remedies, i.e., anticonvulsant, anxiolytic, analgesic, antidepressant. This work constitutes a literature review on medicinal plants showing anticonvulsant properties. The review refers to 16 Brazilian plants and a total 355 species, their families, geographical distribution, the utilized parts, method and references. Some aspects of research on medicinal plants and a brief review of the most common animal models to discover antiepileptic drugs are discussed. For this purpose over 170 references were consulted. Keywords: Medicinal plants, Natural products, convulsion, anticonvulsant properties, animal models, review. INTRODUCTION Epilepsy is one of the most common diseases of the brain, affecting at least 50 million persons worldwide (Scheuer & Pedley, 1990). Epilepsy is a chronic and often progressive disorder characterized by the periodic and unpredictable occurrence of epileptic seizures which are caused by an abnormal discharge of cerebral neurons. Many different types of seizures can be identified on the basis of their clinical phenomena (Löscher, 1998). Seizures are fundamentally divided into two major groups: partial and generalized. Partial (focal, local) seizures are those in which clinical or 798 * E-mail: lucindo@ufs.br Revista Farmacognosia Suplemento 2008.indd Sec1:798 electrographic evidence exists to suggest that the attacks have a localized onset in the brain, usually in a portion of one hemisphere, while generalized seizures are those in which evidence for a localized onset is lacking. Partial seizures are further subdivided into simple partial, complex partial and partial seizures evolving to secondarily generalized seizures, while generalized seizures are categorized into absence (nonconvulsive), myoclonic, clonic, tonic, tonic-clonic and atonic seizures. In addition to classifying the seizures that occur in patients with epilepsy, patients are classified into appropriate types of epilepsy or epileptic syndromes characterized by different seizure types, etiologies, ages ISSN 0102-695X 23/01/2009 10:07:29 Plants with anticonvulsant properties - a review of onset and electroencephalographic (EEG) features (Commission, 2003). The discovery of novel antiepileptic drugs (AEDs) relies upon the preclinical employment of animal models to establish efficacy and safety prior to the introduction of the AEDs in human volunteers (Löscher & Schmidt, 2006). Clearly, the more predictive the animal model for any given seizure type or syndrome, the greater the likelihood that an investigational AED will demonstrate efficacy in human clinical trials (Smith et al., 2007). Mind-altering drugs, especially plants, have always fascinated human beings. Surrounded by mystic superstitions, magic thoughts and religious rituals, they have always occupied man’s attention. Among the plants used by humans, those able to alter the conscience and the sensorium have drawn special consideration. However, the challenge of trying to unravel the mechanisms of action on mood, humor, cognition, ensorium, etc., led to an inconvenience: to ignore, or to face as low priority, the fact that plants could also have beneficial properties to treat mental disease and some psychic ailments (Carlini, 2003; Carlini et al., 2006). Furthermore, as most of the plants were first used by the so-called primitive cultures, their occasional use by the White occidental culture was relegated to a second plan, being considered as sorcerer’s therapeutics. Until recently, very little attention was given by the scientific community to the benefits, as accepted by folk medicine and the medicinal properties of the natural product (Barbosa-Filho et al., 2006a). In addition, nature is a rich source of biological and chemical diversity. The unique and complex structures of natural products cannot be obtained easily by chemical synthesis. A number of plants in the world have been used in traditional medicine remedies (Barbosa-Filho et al., 2006b; Funke & Melzig, 2006; Saúde-Guimarães & Faria, 2007; Agra et al., 2007 and 2008; Veiga-Junior, 2008). Thus, many plants were known for their anticonvulsant activity. Various phytochemical and pharmacological studies have been carried out on these anticonvulsant plants (Chauhan et al., 1988; Nsour et al., 2000). In a previous paper this research group has reviewed crude plant extracts and chemically defined molecules with potential antitumor activity for mammary (Moura et al., 2001), cervical (Moura et al., 2002) and ovarian neoplasias (Silva et al., 2003), as inhibitors of HMG CoA reductase (Gonçalves et al., 2000), central analgesic activity (Almeida et al., 2001), employed in prevention of osteoporosis (Pereira et al., 2002), for the treatment of Parkinson’s disease (Morais et al., 2003), with antileishmanial (Rocha et al., 2005), hypoglycemic (Barbosa-Filho et al., 2005), and antiinflammatory activity (Falcão et al., 2005, Barbosa-Filho et al., 2006c), inhibitors of the enzyme acetylcholinesterase (BarbosaFilho et al., 2006a), inhibitors of the angiotensin converting enzymes (Barbosa-Filho et al., 2006b), giardicidal (Amaral et al., 2006), and antileprotic activity (Barbosa-Filho et al., 2007). The aim of this article is to given an up-todate review on plants with anticonvulsant properties and realized a brief review of the most common animal models to discover antiepileptic drugs. MATERIAL AND METHODS The keywords used for this review were Epilepsy, Plants, Animal models, Anticonvulsant, Natural product and antiepileptic. The search perfound using Chemical Abstracts, Biological Abstracts, Web of Science, ScienceDirect and the data bank of the University of Illinois at Chicago, NAPRALERT (Acronym for NAtural PRoducts ALERT), updated to December 2006. From the literature search, all plants/ herbal preparations that are used ethnomedically to treat epilepsy or those which have been tested for anticonvulsant activity are included in this review. The references obtained were later consulted. RESULTS AND DISCUSSION Over 170 references were found in which plants have been tested for their anticonvulsant activity in in vivo/in vitro studies or clinical studies. Review refers to 355 species, their families, geographical distribution, the utilized parts and methods (see Table 1). The 20th century has witnessed considerable progress in anticonvulsant drug development (Loscher & Schmidt, 1994). The major drugs in clinical use, i.e. phenytoin, carbamazepine, valproate, benzodiazepines, ethosuximide, phenobarbital and primidone, were developed and introduced between 1910 and 1970 and will be referred to as ‘old drugs’ or ‘first generation’ drugs in the following. After a hiatus of over 20 years, several new anticonvulsant drugs, i.e., vigabatrin, gabapentin, felbamate, lamotrigine, oxcarbazepine, tiagabine and topiramate, have been introduced into clinical practice, referred to as ‘new drugs’ or ‘second generation’ drugs in the following. More recent anticonvulsants which are in preclinical or clinical development will be referred to as ‘third generation’ drugs (Löscher, 1998). In the other hand, approximately 70% of patients with epilepsy are well controlled by monotherapy with currently available antiepileptic drugs. Another 5-10% of patients are stabilized by the addition of another antiepileptic drug but there remains over 20% of patients whose seizures are not controlled (Richens & Perucca, 1993). Therefore, phytomedicines can potentially play an important role in the development of new antiepileptic drugs to pharmacoresistent patients (Nsour et al., 2000). Many plants were known for their anticonvulsant activity. Reviews articles (Athanassova Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:799 799 23/01/2009 10:07:29 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. et al., 1965 and 1969; Dhar et al., 1968 and 1973; Adesina, 1982a; Chauhan et al., 1988 and Nsour et al., 2000) were previously published with regards to plants with anticonvulsant properties. In fact, current world-wide interest in traditional medicine has led to rapid development and studies of many remedies employed by various ethnic groups of the world. The information is recorded in alphabetical order of plant scientific name, family, part used, route of administration, dose, method and reference, as showed in Table 1 that summary of the plants which have been tested or reported for anticonvulsant properties. Among those medicinal plants are found to possess anticonvulsant activity in animal models and/or folk medicine, include: Abelmoschus angulosus, Allium sativum, Artemisia spp, Cannabis sativa, Cinchona officinalis, Egletes viscosa, Icacina trichantha, Magnolia grandiflora, Plumbago zeylanica and others. However, a recent study with Brazilian Northeastern plants showed proexcellent results for the species Bauhinia outimouta, Rauvolfia ligustrina and Ximenia americana (Quintans-Júnior et al., 2002). In our review 13 Brazilian plants were cited: Acosmium subelegans, Artemisia verlotorum, Centella asiatica, Cymbopogon citratus, Erythrina velutina, Erythrina mulungu, Hippeastrum vittatum, Lanata microphylla, Licaria puchury-major, Lippia alba, Nepeta cataria, Passiflora alata and Xylopia spp. Among those plants tested, a number of them (from different families) are found to possess anticonvulsant activity. While in most cases, the active constituents are yet to be found, for those where the active components are known, they belong to different chemical classes. However, previous studies showed that some natural plant coumarins and triterpenoids exhibit anticonvulsant properties (Chaturvedi et al., 1974; Nsour et al., 2000). In addition, the history of drug discovery showed that plants are highly rich sources in the search for new active compounds and they have become a challenge to modern pharmaceutical industry. Many synthetic drugs owe their origin to plant-based complementary medicine (Howes et al., 2003; Orhan et al., 2004). A number of animal models have demonstrated utility in the search for more efficacious and more tolerable AEDs. In fact, the models employed in the early phase of AED discovery are highly predictive of subsequent efficacy in easy-to-manage generalized and partial epilepsy (Smith et al., 2007). Thus, animal models more employed were leptazole-induced seizure (LIS), maximal electroshock seizure (MES), metrazoleinduced seizures (MIS), picrotoxin-induced convulsions (PIC), pilocarpine (PILO), pentylenetetrazole (PTZ) and strychnine-induced seizures (SIS). However, MES, PIC and PTZ seizure models continue to represent the three most widely used animal seizure models employed in the search for new AEDs (While et al., 2002). 800 This review only briefly mention the most common animal methods for evaluating of the plants with anticonvulsant properties and medicinal plants studies to epilepsy described in literature. More information, seen an excellence reviews by Mello et al. (1986), Fisher (1989), Meldrum (1997), Nsour et al. (2000) and Smith et al. (2007). Animals models for testing anticonvulsant drugs (Screening) Since the Landmark identification of the anticonvulsant properties of phenytoin in 1936 by virtue of its ability to protect against electroshock-induced convulsions in the cat (Putman & Merritt, 1937) the majority of novel AEDs have been identified through screening in animal models of epilepsy. The National Institutes of Health (NIH)/ American Epilepsy Society (AES) Models II Workshop, held in 2002, described the “ideal” epilepsy model as one that reflects similar pathophysiology and phenomenology to human epilepsy. Seizures should evolve spontaneousl after a postinsult latent period or in a developmental time frame consistent with the human condition. Furthermore, the ideal model should display a pharmacological profile that is resistant to at least two of the existing AEDs (Stables et al., 2003). Finally, the ideal model would be amenable to highthroughput screening. Given the highly heterogeneous nature of seizure disorders in humans, the complexity of the seizure phenotypes, and the syndromes involved, the reality is that it is highly unlikely that any one animal model will ever predict the full therapeutic potential of an investigational AED. Therefore, investigational AEDs are currently evaluated in a battery of syndrome-specific model systems. As specific models are developed (and the drugs they identify are validated clinically), they are integrated into the existing discovery process to better identify more effective antiseizure and potentially antiepileptic therapies. Moving beyond the symptomatic treatment of epilepsy, the goal of most basic and clinical scientists in epilepsy research is to identify therapies capable of preventing, delaying, or modifying the disorder (Smith et al., 2007). The fact that preclinical models used for identification and development of novel drugs have been originally validated by ‘old’ drugs, i.e. conventional anticonvulsants, may explain that several of the new drugs possess mechanisms which do not differ from those of the standard drugs . The MES and PTZ tests The most commonly employed animal models in the search for new anticonvulsant drugs are the maximal electroshock seizure (MES) test and the pentylenetetrazole (PTZ) seizure test (Löscher & Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:800 23/01/2009 10:07:29 Plants with anticonvulsant properties - a review Schmidt, 1988). The maximal electroshock seizure test, in which tonic hindlimb seizures are induced by bilateral corneal or transauricular electrical stimulation, is thought to be predictive of anticonvulsant drug efficacy against generalized tonic-clonic seizures, while the pentylenetetrazole test, in which generalized myoclonic and clonic seizures are induced by systemic (usually s.c. or i.p.) administration of convulsant doses of PTZ, is thought to represent a valid model for generalized absence and/or myoclonic seizures in humans (Löscher, 1998). Everett and Richards (1944) demonstrated that both trimethadione and phenobarbital, but not phenytoin (PHT), were able to block seizures induced by the GABAA-receptor antagonist PTZ. Soon thereafter, Lennox (1945) demonstrated that trimethadione was effective at attenuating petit mal (i.e., absence epilepsy) attacks but was ineffective intreating or worsening grand mal seizures (i.e., generalized tonic-clonic seizures). The positive results obtained in the PTZ seizure test were historically considered suggestive of potential clinical utility against generalized absence epilepsy, based largely on the finding that drugs active in the clinic against spike-wave seizures (e.g., ethosuximide, trimethadione, valproic acid, the benzodiazepines) were effective at blocking clonic seizures induced by PTZ (Smith et al., 2007). MES and PTZ tests provide some insight into the ability of a given drug to penetrate the blood-brain barrier and exert a central nervous system (CNS) effect. Indeed, both models are nonselective with respect to mechanism and therefore are well suited for screening anticonvulsant activity, as neither model assumes that the pharmacodynamic activity of a particular drug is dependent on its molecular mechanism of action (Smith et al., 2007). The pilocarpine (PILO) and kainate (KAI) test Pilocarpine and kainate models replicate several phenomenological features of human temporal lobe epilepsy and can be used as animal preparations to understand the basic mechanisms of epileptogenesis (Turski et al., 1983; Ben-Ari, 1985; Turski et al., 1989). Local or systemic administration of PILO and KAI in rodents leads to a pattern of repetitive limbic seizures and status epilepticus, which can last for several hours (Cavalheiro et al., 1982; Leite et al., 2002). The brain damage induced by status epilepticus in such preparations may be considered an equivalent of the initial precipitating injury event, usually a prolonged febrile convulsion, which is commonly found in patients with mesial temporal lobe epilepsy (Leite et al., 2002). Indeed, neuropathological changes such as neuron loss in several hippocampal subfields and reorganization of mossy fibers into the molecular layer of the fascia dentata are observed in both models and are similar to hippocampi from patients with hippocampal sclerosis (Mello et al., 1993; Mathern et al., 1995). This abnormal synaptic reorganization has been suggested to be an anatomical substrate for epileptogenesis (Buckmaster & Dudek, 1997). Thus, for AED studies in PILO and KAI models, sequential analysis will enable to build precise and reliable correlations between pharmacological effects on seizure behavior and involved brain substrates (Leite et al., 2002). Chemical kindling model Those animal models previously cited are convenient but does not mimic spontaneous seizures occurring in the epileptic brain (Meldrum & Rogawski, 2007). Indeed, kindling model has been widely studied both as a tool for understanding chronic epileptogenesis and as a model for testing AEDs with a potential for treating complex partial seizures. This model is too laborious for use as a primary screening procedure, yet it is clear that it consistently identifies compounds with therapeutic potential in complex partial seizures (Löscher & Schmidt, 2006). The kindling model of epileptogenesis, originally described by Goddard et al. (1969), is characterized by the development of persistent reduction in seizures threshold after a repeated administration of subconvulsant doses of stimulant drugs, such as cocaine, carbamylcholine and pentylenetetrazole (PTZ) (Fabisiak & Schwark, 1982). A well-established model in epilepsy research is PTZ-kindling of mice and rats. PTZ may cause seizures by inhibitory chloride ion channel associated with GABAA receptors (Meldrum & Nilsson, 1976). The mechanism underlying kindling are nowadays still not completely understood (Rössler et al., 2000). As PTZ has been shown to interact with the GABA neurotransmitter and the GABA receptor complex (Löscher & Schmidt, 1988), On the other hand, investigations concerning the biochemistry of glutamate, especially modifications in glutamate binding after electrical kindling, showed increased glutamate release and increased receptor density in target neurons populations (Cincotta et al., 1991). Other studies provided evidence that AMPA and NMDA receptors are involved in the initiation of seizures and their propagation (Velisek et al., 1995) and that NMDA receptors antagonists retard the development of kindling (Becker et al., 2001). Although, little is known about the changes of the glutamatergic neuronal transmission after chemical kindling induced by repeated applications of initially subconvulsive doses of PTZ (Rauca et al., 2000), however, alters in glutamatergic system may not be the main factor but one of several possibilities. Others methods Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:801 801 23/01/2009 10:07:29 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. Summary of the common methods used to evaluation anticonvulsant properties of the medicinal plants and AED as showed in Table 2. In fact, all currently available drugs are anticonvulsant (anti-seizure) rather than antiepileptic. The latter term should only be used for drugs which prevent or treat epilepsy and not solely its symptoms. The goal of therapy with an anticonvulsant drug is to keep the patient free of seizures without interfering with normal brain function (Löscher, 1998). The selection of an anticonvulsant drug is based primarily on its efficacy for specific types of seizures and epilepsy (Mattson, 1995). 802 CONLUSION It can be concluded that studies with species from a range of families have been shown anticonvulsant properties and understanding of the complex mechanism of epilepsy. Academic institutions should invest in this type of study with medicinal plants and contribute to the benefit of the populations needing this type of health care. Thus, it is the wish of the authors that this review article will stimulate the interests in further investigations into natural products for new antiepileptic agents. Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:802 23/01/2009 10:07:29 803 23/01/2009 10:07:29 Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Plant Family Part used Place Abelmoschus angulosus Abrus precatorius Abrus precatorius Acanthus longifolius Achillea millefolium Aconitum species Acorus calamus Acosmium subelegans Adonis vernalis Afraegle paniculata Albizia lebbek Albizia zygia Allium ascalonicum Allium cepa Allium sativum Alstonia boonei Alstonia schoaris Annona muricata Apium graveolens Acorus calamus Acorus gramineus Afraegle paniculata Afrormosia laxiflora Akebia species Albizia lebbek Allium ascalonicum Allium cepa Allium sativum Alstonia boonei Altingia excelsa Anagallis arvensis Angelica pancicii Annona diversifolia Annona muricata Apium graveolens Areca catechu Armillaria mellea Artemisia absinthium Artemisia verlotorum Artemisia vulgaris Asarum heterotropoides Asarum himalaycum Asarum ichangense Asparagus officinalis Asparagus verticillatus Asperula odorata Asplenium trichomanes Malvaceae Leguminosae Fabaceae Acanthaceae Asteraceae Ranunculaceae Araceae Leguminosae Ranunculaceae Rutaceae Leguminosae Leguminosae Liliaceae Liliaceae Liliaceae Apocynaceae Apocynaceae Annonaceae Umbelliferae Araceae Araceae Rutaceae Fabaceae Lardizabalaceae Fabaceae Liliaceae Liliaceae Liliaceae Apocynaceae Hamamelidaceae Primulaceae Apiaceae Annonaceae Annonaceae Apiaceae Palmae Tricholomataceae Asteraceae Asteraceae Asteraceae Aristolochiaceae Aristolochiaceae Aristolochiaceae Liliaceae Liliaceae Rubiaceae Aspleniaceae Aerial Parts Root Root Entire Plant Aerial Parts Aerial Parts Root, Stem Leaf, Root Leaf Shallot Bulb Bulb Stem Stem Flower Rhizome Rhizome Rootbark Root Dried Stem Leaf Flower Bulb Bulb Stembark Entire Plant Entire Plant Aerial Parts Leaf Leaf Seed Aerial Parts Whole Plant Leaf, Stem Whole Plant Whole Plant Whole Plant Aerial Parts Aerial Parts Aerial Parts Entire Plant India India Nigeria Bulgaria Bulgaria China Brazil Nigeria India Africa India India India India India India Bulgaria Taiwan Nigeria Nigeria South Korea India Nigeria Nigeria Nigeria Nigeria India Bulgaria Bulgaria Mexico Gabon India China Bulgaria Brazil Israel China China China Bulgaria Bulgaria Bulgaria Bulgaria Route Given ip ip ip ip iv ig ip ip po po ip ip ip ip ip ip ip ip ip ip ip ip ip ip ip ip sc, iv sc ip ip ip ip ip ip ip Dose Method Used References 2-4 mg/ml 2-4 mg/ml 100, 500, 1000 mg/kg 2-4 mg/ml 5 mg/kg 150,250 mg/kg 250 mg/kg 1 mg/kg 10, 20, 40, 80 mg/kg 2-4 ml/kg 4 ml/kg 200 mg/kg 100, 250 mg/kg 0.73; 1 ml/kg10-20 ml/kg; 25 mg/kg 2-4 ml/kg 0.2 ml/animal 4 ml/kg 4 ml/kg 4 ml/kg 2-4 ml/kg ACV LIS, SIS MIS MIS, MES ACV, MES AVC MIS MES, PTZ AVC LIS, ACV PIC, PTZ, MIS LIS, SIS LIS LIS, SIS LIS LIS LIS LIS, SIS ACV ACV, MES, PTZ PTZ ACV, MIS MES, PIC ACV MES, PTZ, PIC MIS MIS ACV, MIS MIS ACV MIS, SIS MIS ACV, PTZ PTZ PTZ, MES, MIS ACV ACV PTZ, MES, PILO MES, PILO, 3-MCAIC PIC ACV ACV ACV LIS, MIS MIS, SIS MIS, SIS MES, MIS, SIS Bhakuni et al., 1988 Adesina, 1982a Adesina, 1982a Rousinov et al., 1966 Athanassova et al., 1965 Ameri, 1997 Chauhan et al., 1988 Vieira et al., 2002 Chauhan et al., 1988 Ameri, 1997 Kasture et al., 1996 Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Chauhan et al., 1988 Rousinov et al., 1966 Liao et al., 1998 Adesina & Ette 1982 Haruna, 2000 Hong et al., 1988 Kasture et al., 1996 Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Singh et al., 1985 Rousinov et al., 1966 Rousinov et al., 1966 Gonzalez-Trujano, 1998 N’gouemo et al., 1997 Kulshrestha et al., 1970 Lodge et al., 1997 Junhua et al., 1990 Athanassova et al., 1965 Lima et al., 1993 Abdul-Ghani et al., 1987 Sun et al., 1991 Sun et al., 1991 Sun et al., 1991 Chauhan et al., 1988 Athanassova et al., 1969 Athanassova et al., 1969 Athanassova et al., 1965 Plants with anticonvulsant properties - a review Revista Farmacognosia Suplemento 2008.indd Sec1:803 Table 1. Plant showed anticonvulsant properties. 804 Family Part used Place Route Given Dose Method Used 23/01/2009 10:07:29 Atractylodes lancea Astragalus centralpinus Atractylodes lancea Baccharis serraefolia Basslla alba Basslla ruba Bauhinia outimouta Berberis lycium Boerhavia diffusa Bupleurum chinense Bupleurum falcatum Butea monosperma Buthus martensii Cadia rubra Caesalpinia bonduc Caesalpinia bonducella Calliandra portoricensis Cannabis sativa Asteraceae Leguminosae Asteraceae Asteraceae Basellaceae Basellaceae Fabaceae Berberidaceae Nyctaginaceae Apiaceae Apiaceae Fabaceae Buthidae Fabaceae Leguminosae Fabaceae Leguminosae Cannabinaceae Rhizome Leaf Leaf, Stem Leaf, Stem Whole Plant Root Leaf Entire Plant Root Flower Venom Leaf Root, Stem Leaf Root, Stem Whole Plant Japan China Mexico India India Brazil India Nigeria China China/Japan India China Madagascar Nigeria Nigeria Bulgaria po ip ip ip po po ip ip ip ip ip, po ip ip ip ip ip,po, sc 250, 500 mg/kg 500 mg/kg 200 mg/kg 150 mg/kg 25 mg/kg 2 mg/kg 1,5 mg/kg 50, 200 mg/kg 100 mg/kg 100, 300 mg/kg 2-4 ml/kg MES HIC MIN, PTZ, PIC PIZ, SIS LIS, SIS LIS, SIS PTZ MES ACV, PTZ, MES, MIS ACV ACV MES, PTZ, SIS ACV PTZ LIS, SIS MES, MIS, SIS LIS, MIS, SIS ACV, PTZ, MES, KID Canscora decussata Capparis baduca Capsella bursa-pastoris Capsicum annum Carica papaya Carthamus tinctorius Casimiroa edulis Gentianaceae Capparaceae Brassicaceae Solanaceae Caricaceae Asteraceae Rutaceae Whole Plant Entire Plant Flower Root Flower Leaf Bulgaria Nigeria Japan Mexico po ip sc po, sc 2-4 ml/kg 20, 100 mg/kg 10 mg/kg 10, 100 mg/kg ACV ACV MES, MIS LIS, SIS MES, LIS, SIS MIS MES, MIS Cassia siamea Centella asiatica Fabaceae Apiaceae Leaf Aerial Part, Entire Plant Thailand Nigeria, India, Brazil ip ip -, 500 mg/kg MIS, SIS LIS, PTZ, SIS Cerbera odollam Chaerophyllum bulbosum Chelidonium majus Chrysanthemum indicum Cimicifuga dahurica Cimicifuga simplex Cinnamomum cassia Cinnamomum loureirii Cinnamomum zeylanicum Cinchona officinalis Cissampelos pareira Cistus villosus var.tauricus Citrus aurantifolia Citrus aurantium Citrus bergamia ssp. vulgaris Clausena anisata Cleome cileata Clerodendrum colebrookianum Apocynaceae Apiaceae Papaveraceae Asteraceae Ranunculaceae Ranunculaceae Lauraceae Lauraceae Lauraceae Rubiaceae Menispermaceae Cistaceae Rutaceae Rutaceae Rutaceae Rutaceae Capparidaceae Verbenaceae Leaf Aerial Part Aerial Part Flower, Stem Root Rhizome Bark Bark Bark Root Aerial Part Peel, Flower Peel Flower Root, Stem Leaf Leaf Vietnam Bulgaria França Bulgaria Russia China China China China Nigeria Bulgaria Italy Nigeria Nigeria India 10 mg/kg 2-4 ml/kg 9.5 mg/kg 0.25 mg/kg 0.5, 1, 2 mg/kg 2 mg 0.3% 1 mg/kg 4 ml/kg 800 mg/kg 20,40 mg/kg 150, 250 mg/kg 55, 68 mg/kg 40 mg/kg PTZ MES, MIS, SIS MES, PTZ MÊS, SIS SIS MIS, SIS ACV ACV, MIS ACV ACV MIS, LIS, SIS MES, MIS, SIS LIS, SIS LIS, SIS PTZ MIS, PTZ, SIS MES, PTZ SIS ip ip ip ip ip po po po ip ip ip ip ip ip ip References Yamahara et al., 1977 Chauhan et al., 1988 Chiou et al., 1997 Tortoriello et al., 1996 Adesina, 1982a Adesina, 1982a Quintans-Júnior et al., 2002 Dhar et al., 1968 Akah & Nwambie, 1993 Wu & Yu, 1984 Narita et al., 1982 Kasture et al., 2000 Liu et al., 1989 Pieretti et al., 1993 Adesina, 1982a Adesina, 1982a Akah & Nwaiwu 1988 Dantas, 2005; Dwivedi & Harbison, 1975 Dikshit et al., 1972 Adesina, 1982a Rousinov et al., 1966 Adesina, 1982a Chauhan et al., 1988 Kasahara et al., 1989 Adesina 1982a; Ruiz et al., 1995 Arunlakshana, 1949 Chauhan et al., 1988; Sudha et al. 2002; De Lucia et al., 1997 Hien et al., 1991 Rousinov et al., 1966 Mahe et al., 1978 Lashev et al., 1981 Nikol-Skaya & Shreter, 1961 Shibata et al., 1980 Narita et al., 1982 Sugaya et al., 1978 Sugaya et al., 1988 Chauhan et al., 1988 Adesina, 1982a Athanassova et al., 1969 Adesina, 1982a Adesina, 1982a Occhiuto et al., 1995 Makanju, 1983 Akah et al., 1993; 1997 Gupta et al., 1998 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:804 Plant Family Part used 805 23/01/2009 10:07:29 Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Cnestis ferruginea Cnestis glabra Cocculus hirsutus Cola acuminata Connarus wightii Consolida orientalis Convolvulus arvensis Convolvulus hirsutus Convolvulus pluricaulis Convolvulus suendermannii Coptis chinensis Corydalis cava Crassostrea gigas Croton zehntneri Coyledon orbiculata Cryptotympana atrata Cucurbita pepo Cuminum cyminum Curcuma amada Curcuma aromatica Cuscuta chinensis Cyathea nilgirensis Cylista scariosa Cymbopogon citratus Cynanchum otophyllum Cynodon dactylon Cyperus articulatus Cyperus rotundus Cystophora moniliformis Cystoseira usneoides Delphinium consolida Delphinium denudatum Desmodium adscendes Dictamnus albus Digitalis ferruginea Digitalis lanata Dillenia indica Diospyros kaki Diospyros peregrine Duboisia leichhardtii Dunaliella tertilecta Echinacea purpurea Echium vulgare Egletes viscosa Elaeocarpus ganitus Verbenaceae Connaraceae Menispermaceae Sterculiaceae Connaraceae Ranunculaceae Convolvulaceae Convolvulaceae Convolvulaceae Convolvulaceae Ranunculaceae Papaveraceae Ostreidae Euphorbiaceae Crussalaceae Cicadidae Cucurbitaceae Apiaceae Zingiberaceae Zingiberaceae Convolvulaceae Cyatheaceae Fabaceae Gramineae Asclepiadaceae Gramineae Cyperaceae Cyperaceae Cystoseiraceae Cystoseiraceae Ranunculaceae Ranunculaceae Leguminosae Rutaceae Scrophulariaceae Scrophulariaceae Dillenciaceae Ebenaceae Ebenaceae Solanaceae Dunaliellaceae Asteraceae Boraginaceae Asteraceae Elaeocarpaceae Rootbark Root, Stem Aerial Part Aerial Part Aerial Part Aerial Part Entire Plant Aerial Part Rhizome Aerial Part Branches Skin Fruit Rhizome Root Entire Plant Aerial Part Root Leaf Rhizome Leaf Rhizome Root Thallus Thallus Aerial Parts Root Leaf Entire Plant Entire Plant Entire Plant Leaf Calix Entire Plant Aerial Parts Flower Entire Plant/Fruit Elettaria cardamomum Eryngium foetidum Erythroxylum spp. Zingiberaceae Apiaceae Erythroxylaceae Seed Leaf Leaf Place Ivory Coast India India Bulgaria Bulgaria Bulgaria India Bulgaria South Korea Bulgaria Japan Brazil South Africa Taiwan Nigeria Iran India China China India India Brazil China Nigeria L. America Nigeria Australia Spain Bulgaria Pakistan Africa Bulgaria Bulgaria Bulgaria India Japan India Spain Bulgaria Brazil India India Jamaica - Route Given Dose Method Used ip ip ip ip ip ip ip ip ip po ip ig ip ip Ig, po ig ip ip po, ip ip ip po ip ip ip ip ip sc sc sc ip ip ig ip 0.7 mg/kg 100 mg/kg 165 mg/kg 4 ml/kg 4, 44 ml/kg 4 ml/kg 4 ml/kg 1 mg/kg 2-4 ml/kg, 4 mg/kg 10% 20,80 mg/kg 50-400 mg/kg 0.5 mg/kg 0.5 ml/mg 500 mg/kg -, 2.5 mg 1 mg/kg 0.25 mg/kg 500 mg/kg 12.5 mg/kg 600 mg/kg 50-2000 mg/kg 6.25 mg/kg 4 ml/kg 400, 600, 800 mg/kg 300 mg/kg 2-4ml/kg 2-4 ml/kg 2-4 ml/kg 400 mg/kg 4 ml/kg 1.2, 100 mg/kg SIS ACV MES, MIS LIS, SIS SIS MES, MIS, SIS ACV, MIS, SIS MIS, SIS ACV, MES MIS, SIS ACV MES ACV ACV, PIC, SIS ACV, PIC, PTZ PIC LIS, SIS MES, PTZ MES ACV ACV MES SIS ACV ACV MES, MIS, PTZ AVC LIS, SIS ACV ACV AVC, MIS, SIS ACV, PIC, PTZ, SIS PTZ ACV ACV, MES ACV, MES MES ACV ACV AVC ACV AVC ACV, MES, MIS, SIS PTZ MES, MIS ig ip - 3, 10 mg/kg 3 ml/kg - ACV PIC MIS References Declume et al., 1984 Chauhan et al., 1988 Das et al., 1964 Adesina, 1982a Dhar et al., 1973 Athanassova et al., 1969 Chauhan et al., 1988, Athanassova et al., 1969 Sharmaxvn et al., 1965 Athanassova et al., 1969 Hong et al., 1988 Athanassova et al., 1965 Bac et al., 1998 Bernardi et al., 1991 Amabeoku et al., 2007 Hsieh et al., 1991 Adesina, 1982a Sayyah et al., 2002 Bhakuni et al., 1969 Li, 1987 Akbar et al., 1985a Dhawan et al., 1977 Dhar et al., 1968 Carlini et al., 1986 Pei et al., 1981 Akah et al., 1997 Ngo Bum et al., 1996 Adesina, 1982a Spence et al., 1979 Vazquez-Freire et al., 1995 Nsour et al., 2000 Raza et al., 2001 N’gouemo et al., 1996 Athanassova et al., 1965 Athanassova et al., 1965 Athanassova et al., 1965 Bhakuni et al., 1969 Fukuda & Shibata, 1994 Singh et al., 1985 Nsour et al., 2000 Laguna et al., 1990 Nsour et al., 2000 Nsour et al., 2000, Souza et al., 1998 Bhattacharya et al., 1975 Dasgupta et al., 1984 Shukia et al., 1987 Simon, 1986 Adesina, 1982a Plants with anticonvulsant properties - a review Revista Farmacognosia Suplemento 2008.indd Sec1:805 Plant 806 Family Part used Place Route Given Dose Method Used Erythraea centaurium Erythrina velutina Erythrina mulungu Euphorbia antiquorum Euphorbia dracunculoides Euphorbia hirta Euphorbia pilulifera Euphorbia tirucalli Evolvulus nummularius Gentianaceae Fabaceae Fabaceae Euphorbiaceae Euphorbiaceae Euphorbiaceae Euphorbiaceae Euphorbiaceae Convolvulaceae Aerial Parts Stem Bark Stem Bark Whole Plant Entire Plant Whole Plant Whole Plant Aerial Part Entire Plant Bulgaria Brazil Brazil India India India India ip ip ip ip ip ip ip ip 2-4 ml/kg 200-400 mg/kg 200-400 mg/kg 40 mg/kg 500 mg/kg 250 mg/kg 40, 100 mg/kg CZIZ PTZ, SIS PTZ, SIS MIS ACV, MES ACV ACV ACV, MIS MES, MIS Ferula gummosa Galeopsis ladanum Galicia spp. Galium cruciata Galium sylvaticum Galphimia glauca Galphimia glauca Ganoderma lucidum Garcinia mangostana Gastrodia elata Apiaceae Lamiaceae Galiaceae Rubiaceae Rubiaceae Malpighiaceae Malpighiaceae Ganodermataceae Clusiaceae Orchidaceae Seed Aerial parts Aerial Parts Aerial Parts Aerial Parts Fruit Fruit - Iran poland Bulgaria Mexico Mexico Japan China ip ip ip ip ip sc - 55, 198.3 mg/kg 200 mg/kg 4 ml/kg 500 mg/kg 300 mg/kg 5, 10, 20, 500 mg/kg MES, PTZ PTZ ACV ACV MIS, SIS ACV, LIS, SIS ACV PTZ, SIS ACV ACV, KAI Geranium rotundifolium Ginkgo biloba Gleditsia officinalis Glycyrrhiza glabra Grewia hirsuta Gymnosporia falconeri Haplophyllum perforatum Haplophyllum locosum Haplophyllum spp Hedera rhombea Helianthus annuus Heracleum sibiricum Heracleum vericillatum Herpestris monniera Hippeastrum vittatum Holarrhena floribunda Hoslundia opposita Humulus lupulus Hypericum perforatum Icacina trichantha Ipomoea stans Iris kamaonensis Jatropha curcas Jatropha gossypiifolia Juniperus macropoda Kalanchoe crenata Khaya grandifoliola Kochia prostrate Geraniaceae Ginkgoaceae Fabaceae Fabaceae Tiliaceae Celastraceae Rutaceae Rutaceae Rutaceae Araliaceae Asteraceae Umbelliferae Umbelliferae Scrophulariaceae Amarillydaceae Apocynaceae Lamiaceae Cannabaceae Hypericaceae Icacinaceae Convolvulaceae Iridaceae Euphorbiaceae Euphorbiaceae Cupressaceae Crussalaceae Meliaceae Chenopodiaceae Aerial Parts Rhizome Fruit Rhizome Entire Plant Aerial Parts Seed Seed Leaf Flower Bulbs Leaf Leaf Whole Plant Tuber Wood Entire Plant Root Root, Leaf Fruit Leaf Stembark - Bulgaria Africa China Korea India India South Korea Bulgaria Brazil Nigeria Nigeria Switzerland Greece Nigeria Mexico India India Cameroon Nigeria - ip po ig ip ip ip ip ip ip ip ip ip iv ip ip ip ip - 4 ml/kg 1 mg/kg 500 mg/kg 500 mg/kg 0.1 mg/kg 2-4 ml/kg 50, 354, 398 mg/kg 250, 500 mg/kg 80, 100, 400 mg/kg 375 mg/kg 100 mg/kg 150, 300 mg/kg 50 mg/kg - MES, MIS, SIS ACV ACV ACV SIS MIS CZIC, LIS CZIC, LIS ACV SIS CZIZ, MES MES, PTZ, CZIC, SIS MES, PTZ, CZIC, SIS PTZ MES, PTZ MES, PTZ PTZ PTZ ACV, PTZ, SIS MES, PTZ MES LIS, SIS LIS, SIS ACV PTZ, SIS ACV SIS References Athanassova et al., 1965 Vasconcelos et al., 2007 Vasconcelos et al., 2007 Dey et al., 1968 Bhakuni et al., 1969 Lanhers et al., 1996 Chauhan et al., 1988 Dhar et al., 1968 Dey et al., 1968; Chatterjee 1964 Sayyah et al., 2002 Czarnecki et al., 1993 Chauhan et al., 1988 Chauhan et al., 1988 Chauhan et al., 1988, Tortoriello et al., 1992 Tortoriello, 1993 Kasahara et al., 1987 Kurukawa et al., 1997 Chen, 1977; Chauhan et al., 1988, Hsieh et al., 2001 Athanassova et al., 1969 Rodriguez, 1993 Yen, 1977 Hong et al., 1988 Bhakuni et al., 1971 Bhakuni et al., 1971 Chauhan et al., 1988 Chauhan et al., 1988 Chauhan et al., 1988 Lee et al., 1992 Athanassova et al., 1965 Chauhan et al., 1988 Chauhan et al., 1988 Chauhan et al., 1988 Silva et al., 2006 Akah et al., 1997 Akah et al., 1993 Lee et al., 1993 Ozturk et al., 1996 Asuzu et al., 1990 Contreras et al., 1996 Dhawan et al., 1977 Adesina, 1982a Adesina, 1982a Mishra et al., 1989 Nguelefack et al., 2006 Awe te al., 1997 Chauhan et al., 1988 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:806 Plant 23/01/2009 10:07:29 807 23/01/2009 10:07:29 Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Lactuca sativa Lantana camara Lantana microphylla Laurus nobilis Lavandura stoechas Ledebouriella seseloides Leea indica Leonotis leonurus Leonurus cardiaca Lettsomia setosa Licaria puchury-major Lippia alba Lobelia inflata Lobophytum species Lonchocarpus sericeus Luvunga scandens Lycium species Magnolia grandiflora Magnolia officinalis Magnolia obovata Marsilea rajasthanesis Marrubium peregrinum Marrubium vulgare Maprounea africana Matricaria chamomilla Matricaria recutita Maytenus spp. Melia azedarach Melothria maderaspatana Mentha piperita Mentha suaveolens Mikania cordata Mitragyna africana Momordica balsamina Momordica charantia Moringa oleifera Moringa pterygosperma Nardostachys jatamansi Nepeta cataria Nerium oleander Newboldia leavis Nicotiana tabacum Notopterygium incisum Ocimum americanum Ocimum basilicum Ocimum canun Ocimum gratissimum Ocimum sanctum Oplopanax elatus Family Asteraceae Verbenaceae Verbenaceae Lauraceae Lamiaceae Apiaceae Leeaceae Lamiaceae Lamiaceae Convolvulaceae Lauraceae Verbenaceae Campanulaceae Alcyoniidae Leguminosae Rutaceae Solanaceae Magnoliaceae Magnoliaceae Magnoliaceae Marsileaceae Lamiaceae Lamiaceae Euphorbiaceae Asteraceae Asteraceae Celastraceae Meliaceae Cucurbitaceae Lamiaceae Lamiaceae Asteraceae Rubiaceae Cucurbitaceae Cucurbitaceae Moringaceae Moringaceae Valerianaceae Lamiaceae Apocynaceae Bignoniaceae Solanaceae Apiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Araliaceae Part used Seed Root, Leaf Leaf Leaf Flower Root Leaf Leaf Aerial Parts Aerial Parts Dried Seed Leaf Leaf Root Rootbark Seed Bark Aerial Parts Leaf, Flower Leaf Flower Flower Leaf Root Bark Aerial Parts Leaf Leaf Aerial Parts Stembark Leaf Leaf, Flower Root Root Rhizome Leaf Leaf Leaf Leaf Root Leaf Leaf Leaf Leaf Entire Plant Root Place Egypt Brazil Iran Africa China India South Africa Bulgaria India Brazil Brazil Sclotand Australia India South Korea Mexico China,Japan Bulgaria Bulgaria Congo Bulgaria USA, Europe Brazil Nigeria India Spain Spain Nigeria Nigeria Nigeria Nigeria Nigeria India Brazil Pakistan Nigeria Nigeria China Nigeria Nigeria Thailand Nigeria India China Route Given po iv ip ip ip ip ip ip ip ip po ip ig ip ip ip ip ip iv ip, po ip po ip ip ip ip ip ip ip In ration ip ip ip ig ip ip ig ip - Dose 2.5 ml/kg 10 ml/kg 600 mg/kg 125 mg/kg 200 mg/kg 2-4 ml/kg 500 mg/kg 200 mk/kg 200 mg/kg, 1g/kg 10 ml 100 mg/kg 1 mg/kg 10 mg/kg 4 ml/kg 2-4 ml/kg 2-4 ml/kg 0.7, 10 ml/kg 200 mg/kg 400 mg/kg 400 mg/kg 10 % 50 mg/kg 100, 145, 186 mg/kg 20-50 mg 1mg - Method Used PTZ LIS, SIS LIS, SIS ACV PTZ ACV SIS ACV ACV, MES, SIS MES MES SIS, PIC ACV MIS LIS, SIS ACV ACV MES ACV SIS, PIC ACV MES, MIS ACV, CZIC, MES ACV, MES, PTZ, PIC CZIC, MES, PIC PTZ TCES, PTZ MIS, SIS ACV ACV ACV MES SIS LIS, SIS LIS, SIS LIS, SIS MIS, SIS ACV PTZ, SIS ACV MES, PTZ LIS, MIS, SIS ACV LIS LIS SIS LIS, SIS ACV ACV References Said et al., 1996 Chauhan et al., 1988 Adesina, 1982a Sayyah et al., 2002 Gilani et al., 2000 Yen, 1977 Dhar et al., 1968 Beinvenu et al., 2002 Adesina, 1982a Bhakuni et al., 1971 Carlini et al., 1983 Barros Viana et al., 2000 Bhakuni et al., 1971 Baird-Lambert et al., 1980 Chauhan et al., 1988 Mishra et al., 1988 Hong et al., 1988 Ramirez et al., 1998 Watanabe et al., 1983 Chauhan et al., 1988 Chauhan et al., 1988 Athanassova et al., 1965 Chauhan et al., 1988, N’gouemo et al., 1994a Athanassova et al., 1969 Viola et al., 1995 Oliveira et al., 1991 Adesina, 1982a Sinha et al., 1997 Leslie, 1978 Moreno et al., 2002 Moreno et al., 2002 Aji et al., 2001 Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Debelmas et al., 1976 Massoco et al., 1995 Zia et al., 1995 Olajide et al., 1997 Chauhan et al., 1988 Yen, 1977 Adesina, 1982a Adesina, 1982a Ketusingha et al., 1950 Adesina, 1982a Sakina et al., 1990 Qu et al., 1984 Plants with anticonvulsant properties - a review Revista Farmacognosia Suplemento 2008.indd Sec1:807 Plant 808 Family Part used Place Route Given Dose Method Used Ostrea species Pachyma species Paconia radiz Paeonia alba Paeonia albiflora Paeonia albiflora Paeonia emodi Paeonia japonica var. pilosa Paeonia rubra Palisota ambigua Panax ginseng Ostreidae Polyporaceae Paconiaceae Paeoniaceae Paeoniaceae Paeoniaceae Paeoniaceae Paeoniaceae Paeoniaceae Commelinaceae Araliaceae Fruit Root Root Root Root Root Root Root Leaf Root, Leaf Japan South Korea Japan South Korea China Japan India South Korea South Korea Gabon China ig po ig po ig Ig ip ip ip ip 1 mg/kg 1 mg/kg 800 mg/kg 6 mg 100 mg/kg 10 mg/kg 2, 20 mg/kg 1 mg/kg 50 mg/kg 100, 200 mg/kg PTZ ACV ACV ACV ACV PTZ MIES, MIS PIC, SIS ACV PTZ MIS, PIC Patrina intermedia Passiflora alata Passiflora incarnata Pausinystalia yohimbe Persea indica Phaeodactylum tricoenutum Picnomon acarna Picrorhiza kurroa Pimpinella anisum Pinellia ternata Piper guineense Piper logum Piper methysticum Piper nigrum Piscidia erythrina Pistacia integerrima Pithecellobium samon Plectranthus amboinicus Plumbago zeylanica Polygala sabulosa Polypodium vulgare Portucala oleracea Prunus spinosa Psidium guyanensis Psidium pohlianum Pterocarpus santalinus Qingyangshen Valerianaceae Passifloraceae Passifloraceae Rubiaceae Lauraceae Fragilaricaceae Asteraceae Scrophulariaceae Apiaceae Araceae Piperaceae Piperaceae Piperaceae Piperaceae Fabaceae Anacardiaceae Leguminosae Lamiaceae Plumbaginaceae Polygalaceae Polypodiaceae Portulacaceae Rosaceae Myrtaceae Myrtaceae Fabaceae Asclepiadaceae Dried Leaf Leaf Bark Leaf Entire Plant Fruit Tuber Flower Fruit Flower Flower Bark Entire Plant Root Whole Plant Root Whole Plant Fruit Leaf Leaf Stem Root Brazil Italy Canary Islands Spain India Bulgaria China Nigeria China Fiji China USA India Cuba Nigeria Brazil India India Brazil Brazil India China ip ip ip ip ip po ip ip ip ip ip ip ip ip ip ip ip ig po ig ip 75, 150 mg/kg 160 mg/kg 2 mg/kg 150 mg/kg 500 mg/kg 2-4 ml/kg 5 mg 3.4, 263.4 mg/kg 140 mg/kg 2 mg/kg 900 mg/kg 1 ml/kg 250, 500, 1000 mg/kg 100 mg/kg 1.5 mg/kg 400 mg/kg - SIS MIS PTZ ACV PTZ PTZ ACV MIS SZIC, MES ACV MIS, NMDLAIC ACV, MES, PIC, PTZ SIS ACV, NMDLAIC PTZ PTZ PIC ACV LIS PTZ MES, PTZ LIS, SIS PTZ PTZ, PIC, SIS PTZ MES KAI, ACV Rauvolfia ligustrina Apocynaceae Root, Aerial Brazil ip, po 125, 250 mg/kg PTZ, PIC, SIS Rauvolfia schueli Rauvolfia serpentina Rauvolfia tetraphylla Rauvolfia vomitoria Rehmannia glutinosa Rheum officinale Rhodiola rosea Apocynaceae Apocynaceae Apocynaceae Apocynaceae Scrophulariaceae Polygonaceae Crassulaceae Root, Stem Bark Entire Plant Root Root Rhizome - India India Nigeria South Korea China - ip sc 500 mg/kg 1 mg/kg - ACV ACV MES LIS, MIS, SIS ACV ACV SIS References Tsuda et al., 1998 Hong et al., 1988 Tsuda et al., 1997 Hung et al., 1983 Narita et al., 1982 Sugaya et al., 1991 Ahmad et al., 1981 Hong et al., 1979 Hong et al., 1988 N’gouemo et al., 1994b Takagi, 1977; Mitra et al., 1996 Chauhan et al., 1988 Oga et al., 1984 Speroni et al., 1988 Chermat et al., 1979 Mazzanti et al., 1993 Laguna et al., 1990 Chauhan et al., 1988 Debelmas et al., 1976 Athanassova et al., 1969 Narita et al., 1982 Abila et al., 1993 Pei, 1983 Klohs et al., 1959 Hu & Davies, 1997 Klohs et al., 1959 Ansari et al., 1993 Chauhan et al., 1988 Buznego et al., 1999 Adesina, 1982a Duarte et al., 2007 Mannan et al., 1989 Adesina, 1982a Mannan et al., 1989 Santos et al., 1997 Santos et al., 1996 Mehta et al., 1979 Kuang et al., 1991; Guo & Kuang, 1993 Quintans-Júnior et al.,2002;2007 Adesina, 1982a Adesina, 1982a Bhakuni et al., 1969 Sokomba et al., 1986 Hong et al., 1988 Yen, 1977 Aksenova et al., 1966 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:808 Plant 23/01/2009 10:07:30 Family Part used Place Route Given Dose Method Used 809 23/01/2009 10:07:30 Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Ricinus communis Rosmarinus officinalis Rubus brasiliensis Rubus ellipticus Ruta chalepensis Euphorbiaceae Lamiaceae Rosaceae Rosaceae Rutaceae Root Entire Plant Entire Plant Leaf Aerial Parts Nigeria Israel Brazil India Mexico ip ip Ip ip 0.2 ml 300 mgkg 450 mg/kg MIS, LIS PIC ACV MES PTZ Roylea elegans Ruta chalepensis Lamiaceae Rutaceae Leaf Usa, Mexico ip ip - ACV MES, PTZ Ruta graveolens Salvadora persica Salvia guaranitica Salvia haematodes Salvia nemorosa Salvia nemorsa Salvia guaranitica Salvia sclarea Salvia transsylvanica Sapindus trifoliatus Satureja clinopodium Schisandra chinensis Scolopendra subspinides Scutellaria baicalensis Securidaca longepedunculata Senecio fuchsii Senecio jacobaea Sepia officinalis Sesbania grandiflora Solanum americana Solanum gilo Solanum indicum Rutaceae Salvadoraceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae Sapindaceae Lamiaceae Schisandraceae Scolopendridae Lamiaceae Polygalaceae Asteraceae Asteraceae Seppidae Fabaceae Solanaceae Solanaceae Solanaceae Aerial Parts Stem Aerial Parts Root Aerial Parts Leaf Aerial Parts Aerial Parts Aerial Parts Seed Aerial Parts Fruit Entire Plant Root Leaf Entire Plant Entire Plant Leaf Leaf, Flower Flower Entire Plant Bulgaria Italy Latin America India Bulgaria Japan Latin America Bulgaria Egypt India Bulgaria South Korea South Korea China Nigeria Bulgaria Bulgaria India India Nigeria Nigeria Nigeria ip im ip ig ip po ip ip Ip ip ip po ip sc ig ip ip ip 2-4 ml/kg 500 mg/kg 500 mg/kg 4 ml/kg 4 ml/kg 500, 1000 mg/kg 4 ml/kg 1.7 mg/kg 3 mg 50, 10 mg/kg 2-4 ml/kg 25, 50, 100 mg/kg 40 mg/kg CZIC, MES ACV ACV MES MÊS, MIS, SIS ACV ACV MIS, SIS ACV, PTZ MES MÊS, MIS, SIS ACV PIC, SIS ACV LIS MIS MES, MIS ACV MES ACV, LIS LIS LIS, MIS, SIS Solanum khasianum Solanum macrocarpon Solanum melongena Solanum nigrum Solanaceae Solanaceae Solanaceae Solanaceae Entire Plant Leaf, Flower Leaf, Flower Flower India Nigeria Nigeria Nigeria/Mexico ip ip ip ip 250 mg/kg 255 mg/kg MES LIS, SIS LIS, SIS PTZ, MIS, LIS, SIS Solanum torvum Sphencostylis stenocarpa Spondias monbin Stenochilaena palustris Swertia purpurascens Symphytum officinale Syzygium cumini Tabernaemontana pandacaqui Talinum triangulare Taraxacum spp Teclea simplifolia Ternstroemia pinglei Solanaceae Fabaceae Anacardiaceae Blechnaceae Gentianaceae Boraginaceae Myrtaceae Apocynaceae Portulacaceae Asteraceae Rutaceae Theaceae Flower Seed Flower Entire Plant Entire Plant Root Seed Stem Flower Flower Nigeria Nigeria Nigeria India India Bulgaria Brazil Thailand Mexico ip ip ip ip ip ip ig ip ip 60 mg/kg 375 mg/kg 100 mg/kg 2-4 ml/kg 50 mg/kg 450, 850 mg/kg LIS LIS LIS, SIS SIS MES, MIS CZIC, MES PTZ PTZ LIS, SIS ACV ACV PTZ, SIS References Adesina, 1982a Abdul-Ghani et al., 1987 Nogueira et al., 2000 Rana et al., 1990 Aguilar-Santamaria et al., 1996 Chauhan et al., 1988 Aguilar-Santamaria et al., 1996 Athanassova et al., 1969 Monforte et al., 2002 Viola et al., 1997 Akbar et al., 1984a Athanassova et al., 1965 Sugaya et al., 1988; 1997 Viola et al., 1997 Athanassova et al., 1965 Maklad et al., 1997 Gupta et al., 1996 Athanassova et al., 1965 Baek et al., 2000 Hong, 1976 Narita et al., 1982 Ojewole, 2000 Stoyanov et al., 1981 Athanassova et al., 1969 Reddy et al., 1994 Kasture et al., 2002 Adesina, 1982a Adesina, 1982a Dey et al., 1968; Adesina, 1982a Dhar et al., 1968 Adesina, 1982a Adesina, 1982a Adesina 1982a; Perez et al. 1998 Adesina, 1982a Asuzu, 1986 Adesina, 1982a Dhar et al., 1973 Dhar et al., 1973 Athanassova et al., 1969 De Lima et al., 1998 Taesotikul et al., 1998 Adesina, 1982a Chauhan et al., 1988 Chauhan et al., 1988 Aguilar-Santamaria et al., 1996 Plants with anticonvulsant properties - a review Revista Farmacognosia Suplemento 2008.indd Sec1:809 Plant 810 Family Tetrapleura tetraptera Fabaceae Tetraselmis suecica Thalictrum thumbergii Thalictrum hernandezii Theobroma cacao Tilia species Trema guineensis Trema orientalis Triticum aestivum Uncaria rhynchophylla Uncaria sinensis Valeriana angustifolia Valeriana fauriei Valeriana jatamansi Valeriana latifolia Valeriana officinalis Valeriana sambucifolia Vanda roxburghii Veratrum viride Vernonia gratiosa Vinca erecta Vitex negundo Viscum capense Vithania ashvagandha Withania somnifera Xylopia spp Xylopia aethiopica Xylopia carminative Xylopia frutescens Xylopia grandiflora Xylopia sericea Ximenia americana Zea mays Zingiber officinale Ziziphus jujuba Chlamydomonadaceae Ranunculaceae Ranunculaceae Sterculiaceae Tiliaceae Ulmaceae Ulmaceae Poaceae Rubiaceae Rubiaceae Valerianaceae Valerianaceae Valerianaceae Valerianaceae Valerianaceae Valerianaceae Orchidaceae Liliaceae Asteraceae Apocynaceae Verbenaceae Loranthaceae Solanaceae Solanaceae Annonaceae Annonaceae Annonaceae Annonaceae Annonaceae Annonaceae Olacaceae Gramineae Zingiberaceae Rhamnaceae Part used Arillus, Fruit Seed Aerial Parts Leaf Seed Leaf Root Root Leaf Rhizome Root Entire Plant Aerial Parts Leaf Stem Root Entire Plant Whole Plant Rhizome Fruit Place Nigeria Usa Bulgaria Gabon Japan China, Austria Japan Nepal Austria France Austria India Taiwan India South Africa India India Brazil Brazil Brazil Brazil Brazil Brazil Brazil Japan Japan Route Given Dose Method Used ip - LIS, MIS, PTZ ip po ip ip -, ip ip ig ip ip ip ip ip ip ip ip ip ip ip ip ip ip ip 400 mg/kg 2-4 ml/kg 0.3, 1 mg/kg 1, 70 mg/kg 2.05, 2.20, 2.50 mg/kg 17.2 500 mg/kg 2.10 mg/kg 50 mg/kg 2.35 mg/kg 500 mg/kg 3 mg/kg 0.15 mg/kg 50, 400 mg/kg 150 mg/kg 2-4 mg/kg PTZ ACV ACV ACV MES PTZ, MÊS, PIC, KAI MIS ACV KAI, PTZ ACV MIS ACV SIS MIS ACV MIS MES ACV PIC, PTZ, SIS ACV LIS, SIS NMDLAIC, PTZ ACV ACV LIS, SIS LIS, SIS LIS, SIS LIS, SIS LIS, SIS LIS, SIS PTZ LIS, SIS ACV PTZ References Nwaiwu & Akah, 1986, Adesina & Sofowora, 1979 Laguna et al., 1993 Chauhan et al., 1988 Chauhan et al., 1988 Marcus et al., 1997 Athanassova et al., 1969 N’gouemo et al., 1994a Chauhan et al., 1988 Tsuda et al., 1986 Hsieh et al., 1999 Chauhan et al., 1988 Pfeifer et al., 1953 Yoshitomi et al., 2000 Debelmas et al., 1976 Pfeifer et al., 1953 Fehri et al., 1991 Pfeifer et al., 1953 Bhakuni et al., 1969 Chauhan et al., 1988 Hyou et al., 2001 Chauhan et al., 1988 Gupta et al., 1990 Amabeoku et al., 1998 Prasad et al., 1968 Singh et al., 1985 Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Adesina, 1982a Quintans-Júnior et al., 2002 Adesina, 1982a Sugaya et al., 1978 Tsuda et al., 1986 Lucindo J. Quintans Júnior, Jackson R.G.S. Almeida, Julianeli T. Lima, et al. Rev. Bras. Farmacogn. Braz J. Pharmacogn. 18 (Supl.): Dez. 2008 Revista Farmacognosia Suplemento 2008.indd Sec1:810 Plant 23/01/2009 10:07:30 Plants with anticonvulsant properties - a review Table 2. Common methods used to induce convulsion in animal models*. (I) Models for acute simple partial seizures: (1) Topical convulsants (a) penicillin (b) bicuculline (c) picrotoxin (d) strychnine (e) cholinergics (f) anticholinergics (2) Acute electrical stimulation of cortical tissue (3) GABA withdrawal (II) Models for chronic simple partial seizures: (1) Cortically implanted metal (2) Crytogenic injury (3) Ganglioside antibody injection (III) Models for complex partial seizure: (1) Kainate (2) Tetanus toxin (3) Injections into area tempesta (4) Kindling model (5) Pilocarpine (IV) Models for generalized tonic-clonic seizures: (1) Genetic (a) Photosensitive baboons (b) Audigenic seizure mice (c) Totterer mice and other seizure-prone mouse strains (d) Genetically epilepsy-prone rats (2) Maximal electroshock (3) Systemic convulsants (a) Pentylenetetrazole (b) Penicillin (c) Other: picrotoxin, bicuculline, methionine, sulfoximine, strychnine (4) Metabolic derangements (V) Models for absence seizures: (1) Thalamic stimulation (2) Bilateral cortical foci (3) Systemic penicillin (4) Gamma-hydroxybutyrate (5) Intraventricular opiates (6) THIP (4,5,6,7-tetrahydroxyisoxazolo-4,5-pyridine-3-ol) (7) Genetic rodent models of absence (VI) Status epilepticus Large amounts of NMDA, kainate, pilocarpine, bicuculline, pentylenetetrazole. * Adapted from Nsour et al., 2000. 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Plants with anticonvulsant properties: a review

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