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

• Published in: Biochemical pharmacology Vol. 78; no. 1; pp. 54 - 61
• Main Authors: Hernández-Abreu, Oswaldo, Castillo-España, Patricia, León-Rivera, Ismael, Ibarra-Barajas, Maximiliano, Villalobos-Molina, Rafael, González-Christen, Judith, Vergara-Galicia, Jorge, Estrada-Soto, Samuel
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2009; Elsevier
• Subjects: Agastache - chemistry; Agastache mexicana; Antihypertensive; Antihypertensive Agents - therapeutic use; Biological and medical sciences; cGMP; Cyclic GMP - physiology; Dose-Response Relationship, Drug; Flavonoids - isolation & purification; Flavonoids - therapeutic use; Glycosides - isolation & purification; Glycosides - therapeutic use; Humans; Ion Channel Gating - drug effects; Medical sciences; Medicine, Traditional; Methanol; Mexico; Nitric oxide; Nitric Oxide - physiology; Pharmacology. Drug treatments; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plants, Medicinal; Potassium Channels - drug effects; Potassium Channels - physiology; Tilianin; Vasodilator Agents - therapeutic use; Mexico; Antihypertensive; cGMP; Tilianin; Nitric oxide; Agastache mexicana; Vasodilator agent; Pharmacognosy; 3',5'-GMP; Ionic channel; Inorganic element; In vitro; Medicinal plant; Labiatae; Opening; Dicotyledones; Angiospermae; Antihypertensive agent; Spermatophyta; Potassium
• ISSN: 0006-2952; 1873-2968; 1873-2968
• DOI: 10.1016/j.bcp.2009.03.016

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.