Luis Arias-Durán1, Samuel Estrada-Soto2, Monserrat Hernández-Morales1, César Millán-Pacheco1, Gabriel Navarrete-Vázquez1, Rafael Villalobos-Molina3, Maximiliano Ibarra-Barajas3, Julio C Almanza-Pérez4. 1. Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Cuernavaca, Morelos, 62209, Mexico. 2. Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Cuernavaca, Morelos, 62209, Mexico. Electronic address: enoch@uaem.mx. 3. Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, 54090, Mexico. 4. Laboratorio de Farmacología, Depto. Ciencias de La Salud, D.C.B.S, Universidad Autónoma Metropolitana- Iztapalapa, Ciudad de México, 09340, Mexico.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases. AIM: To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents. MATERIALS AND METHODS: Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H2O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensive rats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography. RESULTS: Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p < 0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p < 0.05), and their effects where modified by L-NAME (10 μM, nitric oxide synthase inhibitor), by ODQ (1 μM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR. CONCLUSIONS: Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade.
ETHNOPHARMACOLOGICAL RELEVANCE: Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases. AIM: To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents. MATERIALS AND METHODS: Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H2O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensiverats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography. RESULTS: Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p < 0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p < 0.05), and their effects where modified by L-NAME (10 μM, nitric oxide synthase inhibitor), by ODQ (1 μM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR. CONCLUSIONS:Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade.