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Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents
Authors:Sotoing Taïwe Germain  Ngo Bum Elisabeth  Talla Emmanuel  Dawe Amadou  Okomolo Moto Fleur Clarisse  Temkou Ngoupaye Gwladys  Sidiki Neteydji  Dabole Bernard  Djomeni Dzeufiet Paul Désiré  Dimo Théophile  De Waard Michel
Institution:Graduate School of Biotechnology, Institute of Life Sciences and Resources, Kyung Hee University, Yongin 446-701, Republic of Korea.
Abstract:ETHNOPHARMACOLOGICAL RELEVANCE: Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) has been used as a medicine for the treatment of epilepsy, insomnia, dementia and psychotic disorders in Cameroonian traditional medicine. AIM OF THE STUDY: This study was designed to examine whether the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum bauchiense possess antipsychotic and sedative properties in rodents. MATERIALS AND METHODS: The rectal temperature of mice was recorded with a probe thermometer at a constant depth. Novelty-induced rearing behavior is used to evaluate a central excitatory locomotor behavior in mice. The antipsychotic effects of the extracts were assessed using the apomorphine animal model of psychosis. The catalepsy test was tested based on the ability of the leaves extracts of Crassocephalum bauchiense to alter the duration of akinesia by placing the naive mice with both forelegs over a horizontal bar. The extracts of Crassocephalum bauchiense effects were evaluated on sodium pentobarbital-induced sleeping time. In addition, gamma-aminobutyric acid concentrations in the brain treated mice were also estimated. RESULTS: The aqueous extract and the alkaloid fraction from Crassocephalum bauchiense caused dose-dependent inhibition of novelty-induced rearing behavior, decreased the apomorphine-induced stereotypy and fighting, and had significant fall of the body temperature. The aqueous extract prolonged the sodium pentobarbital sleeping time. This prolongation was not reversed by bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors complex. However, the effect of the aqueous extract on sodium pentobarbital-induced sleeping time was blocked by N-methyl-β-carboline-3-carboxamide, a partial inverse agonist of the benzodiazepine site in the GABA(A) receptor complex and flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. In biochemical experiments, the concentration of the inhibitory amino acid, gamma-aminobutyric acid, was significantly increased in the brain of animals treated with the aqueous extract of Crassocephalum bauchiense and sodium valproate. CONCLUSIONS: The results show that the antipsychotic and sedative properties of Crassocephalum bauchiense are possibly mediated via the blockade of dopamine D-2 receptors and GABAergic activation, respectively. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for these neuropharmacological actions and also to identify the active substances present in the extracts of Crassocephalum bauchiense.
Keywords:BBB  blood-brain barrier  BZD  benzodiazepine  c  c    column chromatography  CHCl3  chloroform  CMC  carboxymethyl cellulose  CNS  Central nervous system  CON  control group  DPM  disintegrations per minute  DW  distilled water  DZP  diazepam  EtOAc  ethyl acetate  FAB-MS  fast atom bombardment mass spectrometry  FLU  flumazenil  GABAA  gamma-aminobutyric acid  IC50  Half-maximal inhibitory concentration  ICR  imprinting control region  i  p    intraperitoneal injection  IR  infra-red  MeOH  methanol  n-BuOH  n-butanol  NMR  nuclear magnetic resonance spectroscopy  R  parviflora  Rhus parviflora Roxb    RPME  Rhus parviflora methanol extract  SD  Sprague Dawley  SEM  standard error of the mean  TLC  thin layer chromatography  Ve/Vt  elution volume/total volume
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