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

作者：Hernandez Abreu Oswaldo; Castillo Espana Patricia; Leon Rivera Ismael; Ibarra Barajas Maximiliano; Villalobos Molina Rafael; Gonzalez Christen Judith; Vergara Galicia Jorge; Estrada Soto Samuel^*

来源：Biochemical Pharmacology, 2009, 78(1): 54-61.

DOI：10.1016/j.bcp.2009.03.016

• Agastache mexicana
• Antihypertensive
• Nitric oxide
• cGMP
• Tilianin

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 anti hypertensive effect on spontaneously hypertensive rats (SHR). Tilianin (0.002-933 mu M) induced significant relaxation in a concentration- and endothelium-dependent and -independent manners in aortic rings pre-contracted with noradrenaline (NA, 0.1 mu M), and serotonin (5-HT, 100 mu M). 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 mu M) or 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, 1 mu M) produced a significant change of the relaxant response and activity was markedly inhibited, but not by indomethacin (10 mu M) or atropine (1 mu M). Furthermore, tilianin (130 mu M) provoked a significant displacement to the left in the relaxation curve induced by sodium nitroprusside (SNP; 0.32 nM to 0.1 mu M). Moreover, tilianin induced significant in vitro NO overproduction (1.49 +/- 0.86 mu M 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 mu M) 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 anti hypertensive effect.

• 出版日期2009-7-1