title: Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.
abstract: BACKGROUND
  Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties.
  
  
  OBJECTIVE
  To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors.
  
  
  METHODS
  Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed.
  
  
  RESULTS
  The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1complex is up to 1000-fold more favourable than the Cas X-GABAAcomplex. All ∆G° values obtained for Cas X-D1complexes were more negative than those seen with Cas X-GABAAcomplexes.
  
  
  CONCLUSIONS
  Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil; Department of Pharmacy, Federal University of Piauí, Teresina, Brazil.
authors.forename: Éverton José Ferreira
authors.initials: ÉJF
authors.lastname: de Araújo
authors.affiliation: Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, Brazil.
authors.forename: Antônia Amanda Cardoso
authors.initials: AAC
authors.lastname: de Almeida
authors.affiliation: Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, Brazil.
authors.forename: Oskar Almeida
authors.initials: OA
authors.lastname: Silva
authors.affiliation: Department of Pharmacy, Federal University of Piauí, Teresina, Brazil.
authors.forename: Iwyson Henrique Fernandes
authors.initials: IHF
authors.lastname: da Costa
authors.affiliation: Department of Pharmacy, Federal University of Piauí, Teresina, Brazil.
authors.forename: Luis Mário
authors.initials: LM
authors.lastname: Rezende-Júnior
authors.affiliation: Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, Brazil; Quantum Computational Chemistry Laboratory, Department of Chemistry, State University of Piauí, Teresina, Piauí, Brazil.
authors.forename: Francisco das Chagas Alves
authors.initials: FDCA
authors.lastname: Lima
authors.affiliation: Department of Organic Chemisty, Chemistry Institute, State University of São Paulo Júlio de Mesquita Filho, Araraquara, Brazil.
authors.forename: Alberto José
authors.initials: AJ
authors.lastname: Cavalheiro
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil; Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, Brazil; Department of Biophysics and Physiology, Laboratory of Experimental Cancerology, Federal University of Piauí, Teresina, Brazil. Electronic address: pmpf@ufpi.edu.br.
authors.forename: Paulo Michel Pinheiro
authors.initials: PMP
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D037821:Casearia / Q000737:chemistry*; D003198:Computer Simulation; D003975:Diazepam / Q000494:pharmacology; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D014151:Anti-Anxiety Agents; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010936:Plant Extracts; D003975:Diazepam; D004298:Dopamine
keywords: Acute toxicity; Anxiolytic action; Casearins; Physiological parameters