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

Objective: To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache niexicana 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, 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. 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 4). observed for the extract and tilianin, by using the plus-maze model, was partially prevented in the presence of fiumazenil (a GABA(A)/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 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 A. mexicana, reinforcing its central nervous system uses. where GABA(A)/BZD, but not 5-HT1A receptors are partially involved.