The aim of the study is to assess the hypotensive properties of the hydro-ethanolic crude root extract (CRE), the n-butanol fraction (F-BtOH) and nuatigenin-3-O-beta-chacotriose, from Solanum sisymbriifolium Lam., in adrenal regeneration hypertension + deoxycorticosterone acetate (ARH + DOCA) rats, following a chronic administration. The roots of S. sisymbriifolium Lam. (Solanaceae) were extracted by reflux with ethanol-water 7:3 and the active extract was fractionated by bioassay-guide liquid-liquid separation. Nuatigenin-3-O-beta-chacotriose (B3-1) was identified as the main hypotensive compound from the crude drug by spectroscopic methods. Immature Wistar rats of both sexes were submitted to both surgery and deoxycorticosterone acetate treatment to obtain adrenal regeneration hypertensive rats (ARH + DOCA). Different groups of experimentally induced hypertensive rats were randomly allotted and received during 16 weeks a daily oral administration of 1% saline solution (0.1 mL/100 g body weigh), 100.0 mg/kg of CRE, 10.0, 30.0 and 50.0 mg/kg of F-BtOH, and 1.0 mg/kg of B3-1, respectively. In addition, two groups of ARH + DOCA rats were randomly assigned to receive either B3-1 (1.0 mg/kg/day) or 1% of saline solution (0.1 mL/100 g body weight/day) for 7 weeks and then a cross over procedure was performed in order to complete the 16th-week treatment. After 16 weeks of oral administration of crude root extract (CRE), butanolic fraction (F-BtOH) and nuatigenin-3-O-beta-chacotriose (B3-1) a significant reduction of blood pressure value was induced in hypertensive animals (ARH + DOCA) in comparison to the control group receiving 1% saline solution, at the end of experiment. Administration of B3-1 (1.0 mg/kg/day p.o.) to ARH + DOCA rats provoked a significant reduction of blood pressure, observed gradually from 5th week (p < 0.05) to the end of the 16th week period of treatment (p < 0.01). Moreover, in a cross over design it was observed that the reduction of blood pressure to normotensive condition is associated to B3-1. The latest demonstrated that the blood pressure-lowering effect, in clearly hypertensive animals, is reversible and depend upon administration of nuatigenin-3-O-beta-chacotriose (B3-1). Our results demonstrated that daily oral administration of CRE, F-BtOH and nuatigenin-3-O-beta-chacotriose from S. sisymbriifolium for a 16-week period exhibits an antihypertensive effect in experimentally hypertensive (ARH + DOCA) rats. (C) 2011 Elsevier GmbH. All rights reserved.