Depressant effects of Agastache mexicana methanol extract and one of major metabolites tilianin

ObjectiveTo 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.MethodsTilianin (30 to 300 mg/kg, ip. and 300 mg/kg, po.) 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.ResultsMethanol 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 WAY 100635 (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.ConclusionsResults indicate that tilianin is one of the bioactive metabolites in the anxiolytic–like activity of A. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5–HT1A, receptors are partially involved.