摘要
Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABA_A/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin(30 to 300 mg/kg.ip.and 300 mg/kg,pa.) and methanol crude extract(10 to 300 mg/kg,ip.and 300 mg/kg po.) from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital(SP)-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil(a GABA_A/BZD antagonist,5 mg/kg ip.) but not in the presence of WAY100635(a selective 5-HT_(1A) receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABA_A/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABA_A/BZD,but not 5-HT_(1A),receptors are partially involved.
Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana（A.mexicana）.Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABAA/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin（30 to 300 mg/kg.ip.and 300 mg/kg,pa.） and methanol crude extract（10 to 300 mg/kg,ip.and 300 mg/kg po.） from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital（SP）-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil（a GABAA/BZD antagonist,5 mg/kg ip.） but not in the presence of WAY100635(a selective 5-HT1A receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABAA/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABAA/BZD,but not 5-HT1A,receptors are partially involved.
基金
partially supported by CONACYT 80811.NC123280 grant
Faculty of Pharmacy Budgets(FECES 2011 and 2012)
