Antihypertensive and vasorelaxant effects of tilianin isolated from Agastache mexicana are mediated by NO/cGMP pathway and potassium channel opening

Tilianin mediates relaxation by an endothelium-dependent manner, probably due to NO release, and also through an endothelium-independent pathway by opening K + channels, both causing the antihypertensive effect. Current investigation was undertaken to elucidate the mode of action of tilianin, isolated from Agastache mexicana, as a vasorelaxant agent on in vitro functional rat thoracic aorta test and to investigate the in vivo antihypertensive effect on spontaneously hypertensive rats (SHR). Tilianin (0.002–933 μM) induced significant relaxation in a concentration- and endothelium-dependent and -independent manners in aortic rings pre-contracted with noradrenaline (NA, 0.1 μM), and serotonin (5-HT, 100 μM). Effect was more significant ( p < 0.05) in endothelium-intact (+E) aorta rings than when endothelium was removed (−E). Pre-treatment with N-nitro- l-arginine methyl ester ( l-NAME; 10 μM) or 1- H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, 1 μM) produced a significant change of the relaxant response and activity was markedly inhibited, but not by indomethacin (10 μM) or atropine (1 μM). Furthermore, tilianin (130 μM) provoked a significant displacement to the left in the relaxation curve induced by sodium nitroprusside (SNP; 0.32 nM to 0.1 μM). Moreover, tilianin induced significant in vitro NO overproduction (1.49 ± 0.86 μM of nitrites/g of tissue) in rat aorta compared with vehicle ( p < 0.05). In addition, pre-treatment with tetraethylammonium (TEA, 5 mM) and 2-aminopyridine (2-AP, 0.1 μM) shifted to the right the relaxant curve induced by tilianin ( p < 0.05). Finally, a single oral administration of tilianin (50 mg/kg) exhibited a significant decrease in systolic and diastolic blood pressures ( p < 0.05) in SHR model. Results indicate that tilianin mediates relaxation mainly by an endothelium-dependent manner, probably due to NO release, and also through an endothelium-independent pathway by opening K + channels, both causing the antihypertensive effect.