title: Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.
abstract: Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of β-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of β-caryophyllene (0, 10, 30, or 100mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that β-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of β-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of β-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil; Department of Nursing, Regional University of Cariri, Crato, CE, Brazil.
authors.forename: Cleide Correia
authors.initials: CC
authors.lastname: de Oliveira
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Clarissa Vasconcelos
authors.initials: CV
authors.lastname: de Oliveira
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Grigoletto
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Leandro Rodrigo
authors.initials: LR
authors.lastname: Ribeiro
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Vinícius Rafael
authors.initials: VR
authors.lastname: Funck
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Ana Cláudia Beck
authors.initials: AC
authors.lastname: Grauncke
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Thaíze Lopes
authors.initials: TL
authors.lastname: de Souza
authors.affiliation: Graduate Program in Food and Science Technology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Naieli Schiefelbein
authors.initials: NS
authors.lastname: Souto
authors.affiliation: Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Food and Science Technology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Furian
authors.affiliation: Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.
authors.forename: Irwin Rose Alencar
authors.initials: IR
authors.lastname: Menezes
authors.affiliation: Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil. Electronic address: ms.oliveira@ufsm.br.
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004831:Epilepsies, Myoclonic / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010433:Pentylenetetrazole; D000081223:Polycyclic Sesquiterpenes; D004856:Postural Balance / Q000187:drug effects; D021641:Recognition, Psychology; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene; D010433:Pentylenetetrazole
keywords: Cannabinoids; Convulsion; EEG; Natural product; PTZ; Phytomedicine