title: Vasorelaxant mode of action of dichloromethane-soluble extract from Agastache mexicana and its main bioactive compounds.
abstract: BACKGROUND
  Agastache mexicana (Kunth) Lint & Epling (Lamiaceae) is a plant used in Mexican traditional medicine for the treatment of hypertension, anxiety and so on.
  
  
  OBJECTIVE
  To determine the vasorelaxant effect and functional mode of action of dichloromethane-soluble extract from A. mexicana (DEAm) and isolate the constituents responsible for the pharmacological activity.
  
  
  METHODS
  Extracts were prepared from the aerial parts of A. mexicana (225.6 g) by successive maceration with hexane, dichloromethane and methanol (three times for 72 h at room temperature), respectively. DEAm (0.01-1000 μg/mL), fractions (at 174.27 μg/mL), acacetin and ursolic acid (UA) (0.5-500 μM) were evaluated to determine their vasorelaxant effect on ex vivo rat aorta ring model. In vivo UA antihypertensive action was determined on spontaneously hypertensive rats.
  
  
  CONCLUSIONS
  DEAm induced a significant vasorelaxant effect in concentration-dependent and endothelium-independent manners (EC50=174.276 ± 5.98 μg/mL) by a calcium channel blockade and potassium channel opening. Bio-guided fractionation allowed to isolate acacetin (112 mg), UA (2.830 g), acacetin/oleanolic acid (OA) (M1) (155 mg) and acacetin/OA/UA (M2) (1.382 g) mixtures, which also showed significant vasodilation. UA significantly diminished diastolic (80 mmHg) and systolic blood pressure (120 mmHg), but heart rate was not modified.
  
  
  CONCLUSIONS
  DEAm produced significant vasorelaxant action by myogenic control cation. The presence of acacetin, OA and UA into the extract was substantial for the relaxant activity of DEAm. In vivo antihypertensive action of UA corroborates the use of A. mexicana as an antihypertensive agent on Mexican folk medicine.
authors.affiliation: a Facultad de Farmacia, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Flores-Flores
authors.affiliation: a Facultad de Farmacia, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Hernández-Abreu
authors.affiliation: b Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: María Yolanda
authors.initials: MY
authors.lastname: Rios
authors.affiliation: b Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Ismael
authors.initials: I
authors.lastname: León-Rivera
authors.affiliation: b Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Berenice
authors.initials: B
authors.lastname: Aguilar-Guadarrama
authors.affiliation: c Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castillo-España
authors.affiliation: c Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Irene
authors.initials: I
authors.lastname: Perea-Arango
authors.affiliation: a Facultad de Farmacia, Universidad Autónoma del Estado de Morelos , Cuernavaca , Morelos , Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
mesh_terms: D031327:Agastache; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008752:Methylene Chloride / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D014665:Vasodilator Agents; D008752:Methylene Chloride
keywords: Acacetin; antihypertensive action; calcium channel blockade; oleanolic acid; ursolic acid