Antihypertensive and vasorelaxant effects of tilianin isolated from Agastache mexicana are mediated by NO/cGMP pathway and potassium channel opening.
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 microM) induced significant relaxation in a concentration- and endothelium-dependent and -independent manners in aortic rings pre-contracted with noradrenaline (NA, 0.1 microM), and serotonin (5-HT, 100 microM). 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 microM) or 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, 1 microM) produced a significant change of the relaxant response and activity was markedly inhibited, but not by indomethacin (10 microM) or atropine (1 microM). Furthermore, tilianin (130 microM) provoked a significant displacement to the left in the relaxation curve induced by sodium nitroprusside (SNP; 0.32 nM to 0.1 microM). Moreover, tilianin induced significant in vitro NO overproduction (1.49 +/- 0.86 microM 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 microM) 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.
Hernández-Abreu
Oswaldo
O
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
Castillo-España
Patricia
P
León-Rivera
Ismael
I
Ibarra-Barajas
Maximiliano
M
Villalobos-Molina
Rafael
R
González-Christen
Judith
J
Vergara-Galicia
Jorge
J
Estrada-Soto
Samuel
S
D031327:Agastache / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000302:isolation & purification / Q000627:therapeutic use*; D006027:Glycosides / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008519:Medicine, Traditional; D000432:Methanol; D008800:Mexico; D009569:Nitric Oxide / Q000502:physiology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D005419:Flavonoids; D006027:Glycosides; D010936:Plant Extracts; D015221:Potassium Channels; D014665:Vasodilator Agents; C426884:tilianin; D009569:Nitric Oxide; D006152:Cyclic GMP; D000432:Methanol