title: Hypotensive mechanism of the extracts and artemetin isolated from Achillea millefolium L. (Asteraceae) in rats.
abstract: Traditional uses of Achillea millefolium L. (Asteraceae) include the treatment of cardiovascular diseases. In the present study, we used anesthetized rats to assess the hypotensive effect of a hydroethanolic extract (HEAM), and its dichloromethane (DCM), ethyl acetate (EA), butanolic (BT), and dichloromethane-2 (DCM-2) fractions, besides the flavonoid artemetin, isolated from A. millefolium. The oral administration of HEAM (100-300 mg/kg), DCM (20mg/kg), DCM-2 (10-30 mg/kg), but not EA (10 mg/kg) and BT (50 mg/kg) fractions significantly reduced the mean arterial pressure (MAP) of normotensive rats. The phytochemical analysis by NMR (1)H of DCM and DCM-2 fractions revealed high amounts of artemetin, that was isolated and administered by either oral (1.5 mg/kg) or intravenous (0.15-1.5 mg/kg) routes in rats. This flavonoid was able to dose-dependently reduce the MAP, up to 11.47 ± 1.5 mmHg (1.5 mg/kg, i.v.). To investigate if artemetin-induced hypotension was related to angiotensin-converting enzyme inhibition, we evaluated the influence of this flavonoid on the vascular effects of both angiotensin I and bradykinin. Intravenous injection of artemetin (0.75 mg/kg) significantly reduced the hypertensive response to angiotensin I while increased the average length of bradykinin-induced hypotension. Artemetin (1.5 mg/kg, p.o.) was also able to reduce plasma (about 37%) and vascular (up to 63%) ACE activity in vitro, compared to control group. On the other hand, artemetin did not change angiotensin II-induced hypertension. Our study is the first showing the hypotensive effects induced by the extract and fractions obtained from A. millefollium. In addition, our results disclosed that this effect may be, at least in part, associated with high levels of artemetin and its ability to decrease angiotensin II generation in vivo, by ACE inhibition.
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: de Souza
authors.forename: Arquimedes
authors.initials: A
authors.lastname: Gasparotto
authors.forename: Sandra
authors.initials: S
authors.lastname: Crestani
authors.forename: Maria Élida Alves
authors.initials: MÉ
authors.lastname: Stefanello
authors.forename: Maria Consuelo Andrade
authors.initials: MC
authors.lastname: Marques
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.forename: Cândida Aparecida Leite
authors.initials: CA
authors.lastname: Kassuya
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000704:Analysis of Variance; D000803:Angiotensin I / Q000009:adverse effects; D000804:Angiotensin II / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D001920:Bradykinin / Q000627:therapeutic use; D005419:Flavonoids / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry / Q000627:therapeutic use; D009822:Oils, Volatile / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005419:Flavonoids; D009822:Oils, Volatile; D010936:Plant Extracts; D000804:Angiotensin II; D008752:Methylene Chloride; C054132:artemetin; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin