Involvement of bradykinin and prostaglandins in the diuretic effects of Achillea millefolium L. (Asteraceae)

Abstract

Ethnopharmacological relevance: Achillea millefolium L. (Asteraceae), popularly known as "mil-folhas", is well recognized and widely used in Brazilian folk medicine to treat heart and kidney disorders. Among its popularly described effects are diuretic and hypotensive actions.

Aim of the study: The diuretic activity of Achillea millefolium L. extracts and its semi-purified fractions, as well as the mechanisms involved, were evaluated in male Wistar rats.

Material and methods: An aqueous extract (AEAM, 125-500 mg/kg), hydroethanolic extract (HEAM, 30-300 mg/kg), dichloromethane subfractions (DCM-2, 10 and 30 mg/kg), or hydrochlorothiazide (10mg/kg), were orally administered and the animals were kept in metabolic cages for 8h for urine collection. To evaluate the involvement of bradykinin and prostaglandins in the diuretic action of Achillea millefolium, selected groups of rats received HOE-140 (1.5mg/kg, i.p.) or indomethacin (5mg/kg, p.o.), before treatment with a DCM-2 subfraction (30 mg/kg). The urinary volume, conductivity, pH, density and electrolyte excretion were measured.

Results: Similar to hydrochlorothiazide, both HEAM and DCM-2, but not AEAM, increased urinary volume and the excretion of Na(+) and K(+) when compared with the control group (vehicle). The diuretic effect of DCM-2 was abolished by HOE-140 (a bradykinin B2 receptor antagonist), as well as by indomethacin (a cyclooxygenase inhibitor).

Conclusion: The present study reveals that extracts obtained from Achillea millefolium are able to effectively increase diuresis when orally administered in rats. This effect depends on both the activation of bradykinin B2 receptors and the activity of cyclooxygenases.

Keywords: ACE; AEAM; ANOVA; Achillea millefolium; Analysis of variance; Angiotensin-converting enzyme; Aqueous extracts of Achillea millefolium L.; B2; Bradykinin B2 receptor; CNPq; COX; COX-1; COX-2; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Cyclooxygenase; Cyclooxygenase type 1; Cyclooxygenase type 2; DCM-2; DEGPP; Dichloromethane subfractions-2 of Achillea millefolium L.; Diretoria Executiva de Gestão da Pesquisa e da Pós-Graduação; Diuresis; Flavonoids; Folk medicine; HCTZ; HEAM; HOE-140; Hydroalcoholic extracts of Achillea millefolium L.; Hydrochlorothiazide; K+; Na+; NaCl; Potassium; Sodium; Sodium chloride; UFPR; UNIPAR; Universidade Federal do Paraná; Universidade Paranaense; d-Arg-[Hyp3, Thi5, D-Tic7, Oic8].