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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, 125–500mg/kg), hydroethanolic extract (HEAM, 30–300mg/kg), dichloromethane subfractions (DCM-2, 10 and 30mg/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 (30mg/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. [ABSTRACT FROM AUTHOR]

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, 125–500mg/kg), hydroethanolic extract (HEAM, 30–300mg/kg), dichloromethane subfractions (DCM-2, 10 and 30mg/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 (30mg/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. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Scutia buxifolia has been widely used in Brazilian folk medicine as an anti-hypertensive agent. We evaluated the vascular effects and mechanism involved in the relaxation of aorta induced by an n-butanolic fraction (BuOH) from Scutia buxifolia. Materials and Methods: Rat aortic rings precontracted by phenylephrine (1μM) were exposed to cumulative concentrations (3–3000μg/ml) of crude extracts or fractions obtained from bark or leaves of Scutia buxifolia. Classical receptor antagonists, channel and enzymatic inhibitors were used to check the mechanisms involved. Results: The crude extracts of both leaves and bark of Scutia buxifolia, as well as several fractions, were able to induce partial or total relaxation of rat aortic rings. The BuOH fraction of bark of Scutia buxifolia was the most potent in endothelium-intact (E+) preparations, and also induced a partial, but very significant relaxation in endothelium-denuded (E−) vessels. The non-selective nitric oxide synthase inhibitor L-NAME, as well as the soluble guanylate cyclase inhibitor ODQ, vanished the relaxation in E+. In E− preparations, K+ channel blockers, such as tetraethylammonium, glibenclamide, 4-aminopyridine, and the large-conductance calcium-activated K+ channel blocker iberiotoxin, were able to significantly reduce the maximum relaxation elicited by BuOH fraction. Conclusion: Our results demonstrated that BuOH fraction obtained from barks of Scutia buxifolia induced both endothelium-dependent and -independent relaxation in rat aortic rings. The endothelium-dependent relaxation is fully dependent on NO/cGMP system, while direct activation of K+ channels may explain, at least in part, the endothelium-independent relaxation induced by BuOH fraction of Scutia buxifolia. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Scutia buxifolia has been widely used in Brazilian folk medicine as an anti-hypertensive agent. We evaluated the vascular effects and mechanism involved in the relaxation of aorta induced by an n-butanolic fraction (BuOH) from Scutia buxifolia. Materials and Methods: Rat aortic rings precontracted by phenylephrine (1μM) were exposed to cumulative concentrations (3–3000μg/ml) of crude extracts or fractions obtained from bark or leaves of Scutia buxifolia. Classical receptor antagonists, channel and enzymatic inhibitors were used to check the mechanisms involved. Results: The crude extracts of both leaves and bark of Scutia buxifolia, as well as several fractions, were able to induce partial or total relaxation of rat aortic rings. The BuOH fraction of bark of Scutia buxifolia was the most potent in endothelium-intact (E+) preparations, and also induced a partial, but very significant relaxation in endothelium-denuded (E−) vessels. The non-selective nitric oxide synthase inhibitor L-NAME, as well as the soluble guanylate cyclase inhibitor ODQ, vanished the relaxation in E+. In E− preparations, K+ channel blockers, such as tetraethylammonium, glibenclamide, 4-aminopyridine, and the large-conductance calcium-activated K+ channel blocker iberiotoxin, were able to significantly reduce the maximum relaxation elicited by BuOH fraction. Conclusion: Our results demonstrated that BuOH fraction obtained from barks of Scutia buxifolia induced both endothelium-dependent and -independent relaxation in rat aortic rings. The endothelium-dependent relaxation is fully dependent on NO/cGMP system, while direct activation of K+ channels may explain, at least in part, the endothelium-independent relaxation induced by BuOH fraction of Scutia buxifolia. [Copyright &y& Elsevier]

Ethnopharmacological relevance Scutia buxifolia , a native tree popularly known as “coronilha”, is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. Aim of the study We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. Material and methods We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10 mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 μl/min), or phenylephrine (4 μg/kg/min), or l -NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2 mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensive rats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100 mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. Results The BuOH soluble fraction of HESB (10 mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6±6.0 and 41.8±8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l -NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6–8 h after a single oral administration of the BuOH soluble fraction of HESB (10 mg/kg), without change in urinary density, pH, or Na + and K + concentrations. In addition, MAP was lower 3 h after the acute oral treatment with the BuOH soluble fraction (82.1±3.8 mm Hg), compared with MAP of animals from the control group (97±3.2 mm Hg). Conclusion This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia , which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats. Material and methods: The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H2O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na+, K+, Cl− and HCO3 − were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined. Results: Water and Na+ excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2′,5′-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment. Conclusion: The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats. Material and methods: The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H2O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na+, K+, Cl− and HCO3 − were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined. Results: Water and Na+ excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2′,5′-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment. Conclusion: The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Pereskia grandifolia Haw. (Cactaceae), popularly known as “ora-pro-nobis” is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action. Materials and methods: The infusions (2.5–10%) and the HEPG (3–100mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na+, K+, Cl− and HCO3 − were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V2 vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined. Results: Water excretion rate was significantly increased by HEPG, while the urinary K+ and Cl− excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment. Conclusion: The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Pereskia grandifolia Haw. (Cactaceae), popularly known as “ora-pro-nobis” is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action. Materials and methods: The infusions (2.5–10%) and the HEPG (3–100mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na+, K+, Cl− and HCO3 − were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V2 vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined. Results: Water excretion rate was significantly increased by HEPG, while the urinary K+ and Cl− excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment. Conclusion: The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Tropaeolum majus L. (Tropaeolaceae) is a medicinal herb popularly used in Brazil for treatment of inflammatory and cardiovascular diseases. Despite some published data on its efficacy, there are still few toxicological data describing the safety of this plant. The aim of this study was to evaluate the (anti)estrogenic and (anti)androgenic activity of the hydroethanolic extract obtained from Tropaeolum majus L. (HETM), as well as its possible effects on uterine contractility. Materials and methods: Three experimental protocols were performed, (a) uterotrophic assay, (b) Hershberger assay and (c) an ex vivo test to investigate the effects of maternal administration of HETM on uterine contractility at the end of pregnancy. In all protocols three doses of the HETM were administered to Wistar rats: 3, 30 and 300mg/kg. Results: In vivo tests for detection of (anti)androgenic and (anti)estrogenic activities did not show any significant alterations. Similarly, no alterations were observed on uterine contractility induced by oxytocin and arachidonic acid. Conclusions: HETM was unable to produce (anti)estrogenic or (anti)androgenic activities in the short-term in vivo screening assays performed. In addition, there was no evidence that HETM can affect uterine contractility following gestational exposure of rats. [Copyright &y& Elsevier]

Abstract: Aim of the study: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE). Methods and methods: Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10–300mg/kg) and TMLR (12.5–100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5–4mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF. Results: The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats. Conclusion: Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE. [Copyright &y& Elsevier]