Phythochemical screening and anticonvulsant activity of Cymbopogon winterianus Jowitt (Poaceae) leaf essential oil in rodents.Abstract
Cymbopogon winterianus (Poaceae) is used for its analgesic, anxiolytic anxiolytic /anx·io·lyt·ic/ (ang?ze-o-lit´ik)
2. an antianxiety agent.
A drug that relieves anxiety. and anticonvulsant properties in Brazilian folk medicine. This report aimed to perform phythochemical screening and to investigate the possible anticonvulsant effects of the essential oil (EO) from fresh leaves of C. winterianus in different models of epilepsy. The phytochemical analysis of EO showed presence of geraniol ge·ra·ni·ol
A fragrant, pale yellow liquid alcohol, C9H17COH, derived chiefly from the oils of geranium and citronella and used in cosmetics and flavorings. (40.06%), citronellal cit·ro·nel·lal
A colorless aromatic liquid, C10H18O, obtained from citronella and certain other essential oils or produced synthetically and used in making perfumes and as a commercial flavoring. (27.44%) and citronellol cit·ro·nel·lol
A colorless liquid, C10H20O, with a roselike odor, derived from any of several essential oils or made synthetically and used extensively in perfumery. (10.45%) as the main compounds. A behavioral screening demonstrated that EO (100, 200 and 400mg/kg; ip) caused depressant depressant, any one of various substances that diminish functional activity, usually by depressing the nervous system. Barbiturates, sedatives, alcohol, and meprobamate are all depressants. Depressants have various modes of action and effects. activity on CNS See Continuous net settlement.
See continuous net settlement (CNS). . When administered concurrently, EO (200 and 400mg/kg, ip) significantly reduced the number of animals that exhibited PTZ-and PIC-induced seizures in 50% of the experimental animals (p < 0.05). Additionally, EO (100, 200 and 400mg/kg, ip) significantly increased (p < 0.05) the latencies of clonic clonic /clon·ic/ (klon´ik) pertaining to or of the nature of clonus.
Of the nature of clonus, marked by contraction and relaxation of muscle. seizures induced by STR STR
synchronous transmitter receiver . Our results demonstrated a possible activity anticonvulsant of the EO.
[C] 2007 Elsevier GmbH. All rights reserved.
Keywords: Cymbopogon winterianus; CNS depressant; Anticonvulsant activity; Pentylenetetrazol; Picrotoxin pic·ro·tox·in
A bitter crystalline compound derived from the seed of an East Indian woody vine and used as a stimulant, especially in treating barbiturate poisoning. ; Strychnine strychnine (strĭk`nĭn), bitter alkaloid drug derived from the seeds of a tree, Strychnos nux-vomica, native to Sri Lanka, Australia, and India.
Epilepsy continues to be a neurological disorder awaiting safer drugs with improved anticonvulsant and anti-epileptogenic effectiveness as currently available drugs fail to provide adequate control of epileptic seizures in about one-third of patients and do not prevent progressive epileptogenic epileptogenic /ep·i·lep·to·gen·ic/ (-lep?to-jen´ik) causing an epileptic seizure.
ep·i·lep·to·gen·ic or ep·i·lep·tog·e·nous
Having the capacity to induce epilepsy. changes are not well understood (Cockerell, 1996). This fact has stimulated a considerable number of research of new anti-epileptic drugs. In this regard, the medicinal plants have been an important source to the development of drugs with this biological activity (Carlini, 2003). Additionally, numerous herbal medicines are recognized as active in the central nervous system (CNS), and they have at least a hypothetical potential to affect chronic conditions such as anxiety, depression, headaches or epilepsy that do not respond well to conventional treatments (Carlini, 2003; Quintans-Junior et al., 2007). In addition, the essential oils are natural products that exhibit a variety of biological properties, such as analgesic (Almeida et al., 2001), anticonvulsant (Almeida et al., 2003) and anxiolytic (Umezu et al., 2002; Almeida et al., 2004).
Cymbopogon winterianus Jowitt (Poaceae), popularly known as "citronella citronella, common name for a grass, Cymbopogon nardus, the source of oil of citronella, used in perfumes and soaps and as an insect repellent. The plant, with bluish green, lemon-scented leaves, is cultivated in Java and Sri Lanka. " and "java grass", is an important essential oil yielding aromatic grass cultivated in India and Brazil. The steam volatile essential oils extracted from its leaves are used in perfumery per·fum·er·y
n. pl. per·fum·er·ies
2. An establishment that makes or sells perfume.
3. The art of making perfume.
Noun 1. , cosmetics, pharmaceuticals, and flavoring industries (Guenther, 1950; Wealth of India, 1985). C. winterianus essential oil is rich in citronellal, geraniol and citronellol (Cassel and Vargas, 2006). However, folk medicine practitioners in the Brazilian Northeast use the infusion of the fleshy leaves for the treatment of epilepsy and anxiety (oral communication). Little information about the plant specie SPECIE. Metallic money issued by public authority.
2. This term is used in contradistinction to paper money, which in some countries is emitted by the government, and is a mere engagement which represents specie. exists. Previous pharmacological study with Cymbopogon citratus has demonstrated the occurrence of CNS effects and anticonvulsant properties (Blanco et al., 2007). The claim of therapeutic success of the plant in the treatment of epilepsy has not been scientifically scrutinized. Preliminary behavioral screening realized in our laboratory of C. winterianus leaf essential oil (EO) showed depressant activity on CNS. The aim of this work was, therefore, to investigate the anticonvulsant effect of EO in rodents.
Materials and methods
Plant material and essential oil (EO) extraction
Leaves were collected from the cultivation of the C. winterianus genotypes established at the Research Station "Campus Rural da UFS UFS Unix File System
UFS Universal Fighting System (Sabertooth games)
UFS United Feature Syndicate
UFS Unite for Sight
UFS Uncoated Free Sheet (paper grade)
UFS Universal Frame System " of the Universidade Federal de Sergipe, Brazil, and a voucher sample has been deposited in the Herbarium herbarium, collection of dried and mounted plant specimens used in systematic botany. To preserve their form and color, plants collected in the field are spread flat in sheets of newsprint and dried, usually in a plant press, between blotters or absorbent paper. of the Department of Biology of Universidade Federal de Sergipe. The leaves of C. winterianus were dried in an oven with air renewal and circulation (model MA-037/18) at 40[degrees]C until complete dehydration has been achieved. The essential oil was obtained by hydrodistillation in a Clevenger-type apparatus using l00g of dried leaves. The oil obtained was dried over anhydrous sodium sulphate, producing yields of 2.34% (v/w). GC-MS analysis were performed in a Shimadzu model QP5050A, according to these experimental conditions; silica capillary column: DB-5MS (30m X 0.25mm X 0.25mm), injector temperature: 230[degrees] C, detector temperature: 250 [degrees]C, temperature program: the column was initially 50 [degrees]C, then raised to 200 [degrees] C at a rate of 4 [degrees]C/min, and finally held at 200 [degrees]C for 10 min, electron impact: 70 eV, carrier gas: helium at 1.2ml/min, scanning speed 0.84 scan [s.sup-1] from m/z 40 to 550 Da. The identification of the components was made through comparison of substance mass spectrum with the database of the GC-MS (NIST (National Institute of Standards & Technology, Washington, DC, www.nist.gov) The standards-defining agency of the U.S. government, formerly the National Bureau of Standards. It is one of three agencies that fall under the Technology Administration (www.technology. 21 and NIST107), literature and retention index (Adams, 2001).
Diazepam diazepam /di·az·e·pam/ (di-az´e-pam) a benzodiazepine used as an antianxiety agent, sedative, antipanic agent, antitremor agent, skeletal muscle relaxant, anticonvulsant, and in the management of alcohol withdrawal symptoms. (DZP), pentylenetetrazole (PTZ), picrotoxin (PIC), phenytoin phenytoin /phen·y·to·in/ (fen´i-toin?) an anticonvulsant used in the control of various kinds of epilepsy and of seizures associated with neurosurgery.
n. (PHE), strychnine (STR), polyonxyethylene-sorbitan monolated (Tween 80) and cremophor was purchased from Sigma (USA) and diazepam (DZP), was obtained from Roche (Brazil). All drugs and the essential oil were administered intraperitoneally (ip) in volumes of 0.1 ml/10g (mice).
Male Swiss mice (25-30 g), 2-3 months of age, were used throughout this study. The animals were randomly housed in appropriate cages at 22 [+ or -]1 [degrees]C on a 12h light/dark cycle (lights on 06:00-18:00) with free access to food (Purina) and water. They were used in groups of 10 animals each. Experimental protocols and procedures were approved by the Universidade Federal de Sergipe Animal Care and Use Committee (CEPA/UFS No.010/07).
The behavioural screening of the mice was performed following parameters described by Almeida et al. (1999) and animals were observed at 0.5, 1, and 2h after administration of EO (100, 200 and 400 mg/kg, ip).
PTZ-and PIC-induced convulsion convulsion, sudden, violent, involuntary contraction of the muscles of the body, often accompanied by loss of consciousness. It is not known what causes the abnormal impulses from the brain that result in convulsive seizures, since the disturbance may arise in normal
Modified method of Vellucci and Webster (1984) was used to assess the anticonvulsant effect of the EO. Mice were kept individually in transparent mice cages (25 cm X 15 cm X 15 cm) for 30 min to acclimatize to their new environment before the commencement of the experiment. Seizures were induced in mice with PTZ (60 mg/kg, ip) or PIC (8 mg/kg, ip) and the animals were observed for convulsion for a period of 15 or 20 min, respectively. The onset of tonic-clonic convulsion and the number of animals convulsing or not convulsing within the observation period were noted. Experiments were repeated following the pretreatment pretreatment,
n the protocols required before beginning therapy, usually of a diagnostic nature; before treatment.
n See predetermination. of animals with either EO, DZP (3 mg/kg, ip) or control vehicle prior to the administration of any of the convulsant con·vul·sant
Causing or producing convulsions.
An agent, such as a drug, that causes convulsions.
a drug which causes convulsions. agents used. The ability of the EO to prevent or delay the onset of tonic and tonic-clonic convulsion by the animals was taken as an indication of anticonvulsant activity (Vellucci and Webster, 1984; Amabeoku and Chikuni, 1993). All experiments were carried out between 9.00 and 15.00 h in a quiet room with an ambient temperature of 22 [+ or -] 1 [degrees] C.
The method has been described previously (Lehmann et al., 1988). In brief, strychnine (STR) convulsions followed by death were induced in male mice by the i.p. injection of 3 mg/kg of the STR nitrate. The treatment of the EO was similarly a PTZ- and PIC-test. A protective effect of the EO given (ip) 1 h prior to STR was recorded and compared to the one of 25 mg/kg PHE and with control group (vehicle). The number of animals, which survived more than l0 min served as criterion of protection. The time to onset of death was recorded in non-protected mice.
The parameters data were evaluated by one-way analysis of variance (ANOVA anova
see analysis of variance.
ANOVA Analysis of variance, see there ) followed by Dunnett's t test. The incidence (%) of clonic or tonic-clonic seizures as well as the mortality were evaluated by Fisher's exact test. Two-factor repeated-measures analysis of variance (ANOVA) of seizures development was performed followed by Tukey's post hoc test. Differences were considered to be statistically significant when p < 0.05.
GC-MS analysis showed a mixture of monoterpenes, being geraniol (40.06%), citronellal (27.44%) and citronellol (10.45%) as the main compounds in the EO (Table 1).
Table 1. Chemical compsition and retention indices of the constituents of the EO RT (min) (a) Compounds (b) (%) I[K.sup.c] 9.992 Limonene 1.58 1027 10.267 -(Z)-Ocimene 0.19 1035 10.642 -(E)-Ocimene 0.09 1045 10.833 Bergamal 0.10 1052 11.558 NI 0.25 1070 12.592 Linalool 0.88 1099 14.383 Isopulegol 0.60 1147 14.525 Citronellal 27.44 1151 14.767 iso-Isopulegol 0.20 1158 14.883 NI 0.09 1161 15.567 NI 0.16 1179 16.533 n-Decanal 0.41 1205 17.192 Citronellol 10.45 1226 17.667 Neral (-Citral) 6.02 1237 18.133 Geranial 40.06 1250 18.750 Geranial (-Citral) 8.05 1267 21.625 Citronelly acetate 0.79 1349 22.600 Geranyl acetate 1.77 1377 24.008 -Caryophyllene 0.55 1418 27.058 -Cadinene 0.23 1512 Total identified 99.41 NI = Not identified. (a) Retention time. (b) Compounds listed in order of elution from an DB-5MS column. (c) Kovats indices were calculated against n-alkanes (C9-C18) on a DB-5MS column.
EO at doses of 100, 200 and 400 mg/kg (ip) showed depressant activity on CNS based on the following behavioral alterations in animals 0.5, 1 and 2 h after treatment: decrease of the spontaneous activity, palpebral palpebral
pertaining to the eyelid.
conjunctiva at the back of the eyelid.
see palpebral fissure. ptosis Ptosis Definition
Ptosis is the term used for a drooping upper eyelid. Ptosis, also called blepharoptosis, can affect one or both eyes.
The eyelids serve to protect and lubricate the outer eye. , ataxia ataxia (ətăk`sēə), lack of coordination of the voluntary muscles resulting in irregular movements of the body. Ataxia can be brought on by an injury, infection, or degenerative disease of the central nervous system, e.g. , analgesia and sedation. These effects were dose dependent.
Effect of EO on PTZ induced convulsions
As shown in Table 2, EO at the doses of 200 and 400 mg/kg (ip) significantly increased the latency period and reduced the frequency of convulsion. The frequency of survival was significantly increased for EO 200 and 400 mg/kg (ip). DZP (3 mg/kg, ip) completely protected the animals against the tonic convulsion elicited by PTZ (60 mg/kg, ip).
Table 2. Effect of EO on convulsion induced by pentylenetetrazol Treatment Dose Latency (s) (a) % Convulsion % Death (mg/kg) Control - 118.7 [+ or -] 14.6 100 80 DZP 3 900.0 [+ or -] 0.0 (b) 0 (c) 0 (c) EO 100 378.2 [+ or -] 165.1 90 90 EO 200 740.2 [+ or -] 115.5 (b) 50 (c) 30 (c) EO 400 649.3 [+ or -] 158.9 (d) 60 (e) 60 (e) n = 10. (a) Values represent mean [+ or -] S.E.M. (b) p < 0.01 (one-way ANOVA and Dunnett's test), significantly different from control. (c) p < 0.01 (Fisher's test), significantly different from control. (d) p < 0.05 (Fisher's test), significantly different from control. (e) p < 0.05 (one-way ANOVA and Dunnett's test), significantly different from control.
Effect of EO on PIC induced convulsions
In the model of convulsion induced by PIC (Table 3), the EO (200 and 400 mg/kg, ip) induced a significant increase in the latency of convulsion in a dose dependant manner. However, an increased frequency of survival was detected with EO at all doses. The DZP group significantly decreased the development of convulsion in comparison with the control group.
Table 3. Effect of EO on convulsion induced by picrotoxin Treatment Dose Latency (s) (a) % Convulsion % Death (mg/kg) Control - 376.2 [+ or -] 7.1 100 90 DZP 3 1.200 [+ or -] 0.0 (b) 0 (c) 0 (c) EO 100 546.3 [+ or -] 75.3 100 70 (d) EO 200 690.1 [+ or -] 80 (d) 80 (d) 50 (c) EO 400 930 3 [+ or -] 91.1 (b) 60 (d) 70 (d) N = 10. (a) Values represent mean [+ or -] S.E.M. (b) p < 0.01 (one-way ANOVA and Dunnett's test), significantly different from control. (c) p < 0.01 (Fisher's test), significantly different from control. (d) p < 0.05 (Fisher's test), significantly different from control. (e) p < 0.05 (one-way ANOVA and Dunnett's test), significantly different from control.
Effect of EO on STR induced convulsions
Table 4 shows in the control group the STR consistently induced convulsion in 100% of 10 mice. On the other hand, the EO (100, 200 and 400 mg/kg, ip) increase the latency of clonic convulsions significantly different from control (p < 0.05), similarly occurs with group received 25 mg/kg (ip) of PHE.
Table 4. Effect of the EO on STR-induced convulsions in mice Treatment Dose Latency (s) (a) % Convulsion % Death (mg/kg) Control - 113.5 [+ or -] 4.4 100 100 DZP 25 592.5 [+ or -] 21.4 (b) 10 (c) 70 (d) EO 100 204 8 [+ or -] 23.5 (e) 100 100 EO 200 173.4 [+ or -] 13.1 (e) 100 100 EO 400 295.2 [+ or -] 19.0 (e) 90 100 n = 10. (a) Values represent mean [+ or -] S.E.M. (b) p < 0.01 (one-way ANOVA and Dunnett's test), significantly different from control. (c) p < 0.01 (Fisher's test), significantly different from control. (d) p < 0.05 (Fisher's test), significantly different from control. (e) p < 0.05 (one-way ANOVA and Dunnett's test), significantly different from control.
In folk medicine of the Brazilian Northeast the Cymbopogon winterianus ("citronella") is used for treatment of epilepsy and anxiety. In pharmacological behavioral screening, the animals treated with C. winterianus leaf essential oil (EO) showed decrease of response to the touch, palpebral ptosis, ataxia, analgesia, sedation and reduction of motor activity. These data are indicative of depressive activity of the CNS according to Almeida et al. (1999).
Pentylenetetrazole, picrotoxin and strychnine are all convulsant agents (Nicoll, 2001; Rang et al., 2003). Data from this study show that the onset of tonic-clonic convulsion produced by PTZ was significantly delayed by EO (as shown in Table 2). The incidence of mortality was significantly reduced (p < 0.05). According to De Sarro et al. (1999), PTZ may be exerting its convulsant effect by inhibiting the activity of gamma aminobutyric acid Noun 1. gamma aminobutyric acid - an amino acid that is found in the central nervous system; acts as an inhibitory neurotransmitter
amino acid, aminoalkanoic acid - organic compounds containing an amino group and a carboxylic acid group; "proteins are (GABA GABA ?.
GABA (gamma-aminobutyric acid)
A neurotransmitter that slows down the activity of nerve cells in the brain. ) at GAB[A.sub.A] receptors. Gamma aminobutyric acid is the major inhibitory neurotransmitter which is implicated in epilepsy. The enhancement and inhibition of the neurotransmission of GABA will attenuate To reduce the force or severity; to lessen a relationship or connection between two objects.
In Criminal Procedure, the relationship between an illegal search and a confession may be sufficiently attenuated as to remove the confession from the protection afforded by the and enhance convulsion, respectively (Meldrum, 1981; Gale, 1992; Westmoreland et al., 1994). Since the EO delayed the occurrence of PTZ convulsion, it is probable that it may be interfering with gabaergic mechanism(s) to exert its anticonvulsant effect.
Picrotoxin exerts its convulsant effect by blocking the GAB[A.sub.A] receptor-linked chloride ion channel which normally opens to allow increased chloride ion conductance into the brain cells following the activation of GAB[A.sub.A] receptors by GABA (Faingold, 1987; Meldrum and Rogawski, 2007). Data from this study show that picrotoxin induced convulsion in mice and that EO significantly (p < 0.05, Table 3) attenuated the convulsion. It is probable that EO attenuated PIC convulsion by enhancing GABA neurotransmission. This further supports the hypothesis that EO may be affecting gabaergic mechanism(s) to exert its anticonvulsant activity.
On the other hand, STR cause convulsions by antagonized glycine receptor, increase postsynaptic postsynaptic /post·sy·nap·tic/ (-si-nap´tik) distal to or occurring beyond a synapse.
Situated behind or occurring after a synapse. excitability and increase ongoing activity in dorsal horn neurons (Game and Lodge, 1975; McGaraughty and Henry, 1998). Our results demonstrate that acute administration with EO on STR induced convulsions increased the latency of seizures significantly different from control (p < 0.05). Therefore, this effect suggest of the possible involvement on glycinergic neurotransmission.
However, experimental studies showed that monoterpenes (eugenol eugenol /eu·gen·ol/ (u´jen-ol) a dental analgesic and antiseptic obtained from clove oil or other natural sources; applied topically to dental cavities and also used as a component of dental protectives. , geraniol, citronellol) has CNS depressant activity, anesthetic, myorelaxant and anticonvulsant properties (Dallmeier and Carlini, 1981; Freire et al., 2006; Sousa et al., 2006). Freire et al. (2006) showed which Ocimum gratissimum essential oil, rich in geraniol or eugenol, possess anticonvulsant properties. Additionally, citronellol is an acyclic a·cy·clic
1. Botany Not cyclic. Used especially of flowers whose parts are arranged in spirals rather than in whorls, as in magnolias.
2. monoterpene alcohol prevalent in essential oils of C. winterianus (Rao et al., 2004) and in other aromatic plant species (Lis-Balchin et al., 1998). Some of the pharmacological actions of citronellol have been studied (Haginiwa et al., 1963; Hierro et al., 2004; Kubo et al., 1993). Citronellol produced also an increasing effect on the response rate during the alarm period in the conflict test suggesting that it possesses an anti-anxiety effect (Umezu et al., 2002). In recent study, citronellol showed to possess anticonvulsant activity due to the reduction of neuronal excitability mainly through the voltage-dependent N[a.sup.+] channels and by facilitation of the inhibitory synaptic input by simply activating GAB[A.sub.A] (Sousa et al., 2006).
These data lead us to conclude both the C. winterianus leaf essential oil (EO) have a CNS depressant activity and anticonvulsant properties. Thus, lend pharmacological justification to the use of the plant infusion by traditional medicine practitioners in the treatment of epilepsy. It may also not be impossible to suggest that the anticonvulsant activity may be exerted via more than one mechanism especially since the EO is thought to affect both gabaergic and glycinergic mechanisms.
We would like to thank the National Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ CNPq/Brazil)) and the Research Supporting Foundation of State of Sergipe (Fundacao de Amparo a Pesquisa do Estado de Sergipe/FAP-SE) for the financial support.
Adams, R.P., 2001. In Identification of Essential Oil Components by Gas Chromatography/Quadrupole Mass Spectroscopy. Carol Stream, IL, Allured.
Almeida, R.N., Falcao, A.C.G.M., Diniz, R.S.T., Quintans-Junior, L.J., Polari, R.M., Barbosa-Filho, J.M., Agra, M.F., Duarte, J.C., Ferreira, C.D., Antoniolli, A.R., Araujo, C.C., 1999. Metodologia para avaliacao de plantas com atividade no sistema nervoso central e alguns dados experimentais. Rev. Bras. Farm. 80 (3/4), 72-76.
Almeida, R.N., Navarro, D.S., Barbosa-Filho, J.M., 2001. Plants with central analgesic activity. Phytomedicine 8, 310-322.
Almeida, R.N., Motta, S.C., Leite, J.R., 2003. Oleos essenciais com propriedades anticonvulsivantes. Bol. Latinoam. Caribe Plantas Med. Aromat. 2, 3-6.
Almeida, R.N., Motta, S.C., Faturi, C.B., Catallani, B., Leite, J.R., 2004. Anxiolytic-like effects of rose oil inhalation on the elevated plus-maze test in rats. Pharmacol. Biochem. Behav. 77, 361-364.
Amabeoku, G.J., Chikuni, O., 1993. Cimetidine-induced seizures in mice: antagonism by some GABAergic agents. Biochem. Pharmacol. 46, 2171-2175.
Blanco, M.M., Costa, C.A.R.A., Freire, A.O., Santos Jr., J.G., Costa, M., 2007. Neurobehavioral effect of essential oil of Cymbopogon citratus in mice. Phytomedicine, in press, doi: 10.1016/j.phymed.2007.04.007.
Carlini, E.A., 2003. Plants and the central nervous system. Pharmacol. Biochem. Behav. 3, 501-512.
Cassel, E., Vargas, R.M.F., 2006. Experiments and modeling of the Cymbopogon winterianus essential oil extraction by steam distillation. J. Mex. Chem. Soc. 50 (3), 126-129.
Cockerell, O.C., 1996. The prognosis of epilepsy. In: Shorvon, S., Dreifuss, F., Fish, D., Thomas, D. (Eds.), The Treatment of Epilepsy. Blackwell Science, Oxford, pp. 97-113.
De Sarro, A., Cecchetti, V., Fravolini, V., Naccari, F., Tabarrini, O., De Sarro, G., 1999. Effects of novel 6-desfluoroquinolones and classic quinolones on pentylenete-trazole-induced seizures in mice. Antimicrob. Agents Chemother. 43, 1729-1736.
Dallmeier, K., Carlini, E.A., 1981. Anesthetic, hypotermic, myorelaxant and anticonvulsant effects of synthetic eugenol derivatives and natural analogues. Pharmacology 22, 113-127.
Faingold, C.L., 1987. Seizures induced by convulsant drug. In: Jobe, P.C., Laird, II, H.E. (Eds.), Naurotransmitters and Epilepsy. The Humana Press, Clifton, pp. 215-275.
Freire, C.M.M., Marques, M.O.M., Costa, M., 2006. Effects of seasonal variation on the central nervous system activity of Ocimum gratissimum L. essential oil. J. Ethnopharmacol. 105, 161-166.
Gale, K., 1992. GABA and epilepsy: basic concepts from preclinical research. Epilepsia 33, S3-S12.
Game, C.J., Lodge, D., 1975. The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated myelinated /my·eli·nat·ed/ (mi´e-li-nat?ed) having a myelin sheath.
Having a myelin sheath.
having a myelin sheath. cutaneous afferents in the cat. Exp. Brain Res. 23, 75-84.
Guenther, E., 1950. In: Guenther, E. (Ed.), Essential Oils. van Nostrand Co., Inc, London.
Haginiwa, J., Harada, M., Morishita, I., 1963. Pharmacological studies on crude drugs. VII. Properties of essential oil components of aromatics and their pharmacological effect on mouse intestine. Yakugaku Zasshi 83, 624-628.
Hierro, I., Valero, A., Perez, P., Gonzalez, P., Cabo, M.M., Montilla, M.P., Navarro, M.C., 2004. Action of different monoterpenic compounds against Anisakis simplex S.1. L3 larvae. Phytomedicine 11, 77-82.
Kubo, I., Muroi, H., Kubo, A., 1993. Antibacterial activity of long-chain alcohols against Streptococcus mutans. J. Agric. Food Chem. 41, 2447-2450.
Lehmann, J., Hutchison, A., McPherson, S.E., Mondadori, C., Schmutz, M., Sinton, C.M., Tsai, C., Murphy, D.E., Steel, D.J., Williams, M., Cheney, D.L., Wood, P.L., 1988. CGS 19755, a selective and competitive N-Metil-D-aspartate-type excitatory amino acid receptor antagonist. J. Pharmacol. Exp. Ther. 246, 65-75.
Lis-Balchin, M., Patel, J., Hart, S., 1998. Studies on the mode of action of essential oils of scented-leaf Pelargonium (Geraniaceae). Phytother. Res. 12, 215-217.
McGaraughty, S., Henry, J.L., 1998. The effects of strychnine, bicuculline, and ketamine ketamine /keta·mine/ (ke´tah-men) a rapid-acting general anesthetic, used as the hydrochloride salt.
n. on immersion-inhibited dorsal horn convergent neurons in intact and spinalized rats. Brain Res. 784 (1), 63-70.
Meldrum, B.S., 1981. GABA agonists as antiepileptic agents. Adv. Biochem. Psychopharmacol. 26, 207-217.
Meldrum, B.S., Rogawski, M.A., 2007. Molecular targets for antiepileptic drug development. Neurotherapeutics: J. Am. Soc. Exp. Neuro. Ther. 4, 18-61.
Nicoll, R.A., 2001. Introduction to the pharmacology of CNS drugs. In: Katzung, B.G. (Ed.), Basic and Clinical Pharmacology, eighth ed. Lange Medical Books/McGraw-Hill, New York, pp. 351-363.
Quintans-Junior, L.J., Silva, D.A., Siqueira, J.S., Souza, M.F.V., Barbosa-Filho, J.M., Almeida, R.N., Silva Junior, R.G.C., 2007. Anticonvulsant properties of the total alkaloid fraction of Rauvolfia rauwolfia, Rauvolfia
any member of the genus Rauwolfia in the plant family Apocynaceae; the dried root, or extract of the dried root, of Rauwolfia; contains reserpine; causes abdominal pain, diarrhea, jaundice, hepatitis; includes R. serpentina, R. ligustrina Roem. et Schult. in male mice. Brazilian J. Pharmacogn. 17 (2), 152-158.
Rang, H.P., Dale, M.M., Ritter, J.M., Moore, P.K., 2003. Pharmacology, fifth ed. Churchill Livingstone, Edinburgh, pp. 585-587.
Rao, B.R.R., Bhattacharya, A.K., Mallavarapu, G.R., Ramesh, S., 2004. Yellowing and crinkling disease and its impact an the yield and composition of the essential oil of citronella (Cymbopogon winterianus Jowitt.). Flavour Frag. J. 19, 344-350.
Sousa, D.P., Goncalves, J.C.R., Quintans-Junior, L.J., Cruz, J.S., Araujo, D.A.M., Almeida, R.N., 2006. Study of anticonvulsant effect of citronellol, a monoterpene alcohol, in rodents. Neurosci. Lett. 401, 231-235.
Umezu, T., Ito, H., Nagano, K., Yamakoshi, M., Oouchi, H., Sakaniwa, M., Morita, M., 2002. Anticonflict effect of rose oil and identification of its active constituents. Life Sci. 72, 91-102.
Vellucci, S.V., Webster, R.A., 1984. Antagonism of caffeine-induced seizures in mice by Ro 15-1788. Eur. J. Pharmacol. 97, 289-293.
Wealth of India, 1985. A dictionary of Indian raw materials and industrial products. In: Raw Materials, vol. 1. A. Publications and Information Directorate CSIR CSIR Council for Scientific and Industrial Research (Ghana)
CSIR Council of Scientific and Industrial Research (India)
CSIR Centre for Scientific and Industrial Research , New Delhi.
Westmoreland, B.F., Benarroch, E.E., Dube, J.R., Regan, T.J., Sandok, B.A., 1994. Medical Neurosciences. Mayo Foundation, Rochester, pp. 307-312.
L.J. Quintans-Junior (a), *, T.T. Souzaa (a), B.S. Leitea (a), N.M.N. Lessaa (a), L.R. Bonjardima, (a) M.R.V. Santosa (a), P.B. Alves (b), A.F. Blank (c), A.R. Antoniolli (a)
(a) Departamento de Fisiologia, Universidade Federal de Sergipe, Campus Universitdrio "Prof. Aloisio de Campos", CEP CEP congenital erythropoietic porphyria.
congenital erythropoietic porphyria 49100-000 Sao Cristovao, SE, Brazil
(b)Departamento de Quimica, Universidade Federal de Sergipe, Campus Universitario "Prof. Aloisio de Campos", CEP 49100-000 Sao Cristovao, SE, Brazil
(c)Departamento de Agronomia, Universidade Federal de Sergipe, Campus Universitario "Prof. Aloisio de Campos", CEP 49100-000 Sao Cristovao, SE, Brazil
* Corresponding author. Tel.: + 55 79 2105 6645; fax: +55 79 210 6474
E-mail addresses: firstname.lastname@example.org, email@example.com (L.J. Quintans-Junior).