Arquimedes Gasparotto Junior

Cardiovascular protective effects of Casearia sylvestris Swartz in Swiss and C57BL/6 LDLr-null mice undergoing high fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE Although Casearia sylvestris Swartz is used in Brazilian folk medicine to treat obesity, no study has been conducted to evaluate the effects of this species in an experimental model of dyslipidemia and atherosclerosis. So, the aim of this study was to evaluate possible hypolipemiant and antiatherogenic activity of the methanolic extract obtained from Casearia sylvestris (MECS) using Swiss and C57BL/6 LDLr-null mice undergoing high fat diet (HFD). MATERIAL AND METHODS Dyslipidemia and atherogenesis were induced by the administration of commercial HFD for 4 weeks. The MECS was administered orally at doses of 250 and 500mg/kg, once a day, for two weeks, starting from the 2nd week of HFD. The gain in body weight and systolic blood pressure (SBP) were measured weekly over the four week study. At the end of the experiments the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were measured by colorimetric method. Aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were also evaluated in collected serum. The renal function, atherogenic index serum (AIS) and in vitro antiplatelet activity were investigated. Additionally, histopathological analyzes were performed to determine the intima-media thickness (IMT) and intima media ratio (IMR) in aorta samples. RESULTS The HFD induced dyslipidemia and major structural changes in the aortic wall, including raising of the systolic blood pressure in LDLr-null mice. In addition, we observed an increase in lipid peroxidation accompanied by a reduction of serum nitrite. The treatment with MECS was able to prevent the increase of SBP, TC, LDL-C, VLDL-C and triglycerides levels and increase HDL-C in Swiss and LDLr-null mice. These effects were accompanied by a significant reduction in oxidative stress. Moreover, AIS, IMT and IMR were significantly reduced in MECS-treated mice, and the extract was able to reduce platelet aggregation in vitro. CONCLUSION This study demonstrated that MECS reduces the serum lipids and oxidative stress when orally administered to Swiss and LDLr-null mice. In addition, it was able to prevent arterial thickening induced by HFD and to inhibit platelet aggregation in vitro.

Evaluation of subchronic toxicity of the hydroethanolic extract of Tropaeolum majus in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE The use of medicinal plants for the treatment of diseases usually comes from the belief that they present low toxicity due their natural origin. However, it is necessary a toxicological and pharmacological evaluation for these plants. Tropaeolum majus is a medicinal plant used in popular medicine to treat several diseases, including cardiovascular disorders, urinary tract infections and asthma. Even though several studies proved its therapeutic effects, there are few toxicological studies with this species. AIM OF THE STUDY The present study was carried out to evaluate the subchronic toxicity of the hydroethanolic extract obtained from leaves of T. majus (HETM) in Wistar rats. MATERIAL AND METHODS Male and female Wistar rats received three doses of HETM (75, 375 and 750 mg/kg) for 28 days. After the treatments biochemical, hematological and histopathological parameters were analyzed. RESULTS No significant alterations in the animals body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys and spleen were observed. CONCLUSIONS These results demonstrate the absence of subchronic toxicity due to oral treatment with HETM for 28 days in Wistar rats. However, other toxicological studies are necessary to evaluate the total safety of this plant.

Anti-inflammatory activity of Agaricus blazei in different basidiocarp maturation phases

Abstract Agaricus blazei Murrill ss. Heinemann (Agaricus brasiliensis Wasser et al.; Agaricus subrufescens Peck) has raised interest in the scientific community due to its therapeutic properties. Although there are numerous studies about this fungus a few of them study the anti-inflammatory activity and the relationship with basidiocarp development phases. Thus, the objective of this study was to evaluate the effect of A. blazei extracts of closed and opened basidiocarp on the cell migration of rats submitted to an inflammatory challenge. The basidiocarp extracts were administered by gavage at 55 or 110 mg/kg. The inflammatory challenge was performed by administering phlogistic agent (carrageenan 2%) in an air-pouch induced in the animal subcutaneous tissue. It was concluded that the extracts affect leukocyte mobilisation regulation; closed basidiocarp extract in doses of 55 and 110 mg/kg and opened basidiocarp extract in 110 mg/kg modulate the anti-inflammatory response.

Increased activation of the Rho-A/Rho-kinase pathway in the renal vascular system is responsible for the enhanced reactivity to exogenous vasopressin in endotoxemic rats.

Objective:We evaluated the role of the renal vascular system and the Rho-A/Rho-kinase pathway in the maintenance of the pressor effects of vasopressin in endotoxemic rats. Design:In vitro and in vivo animal study. Setting:University research laboratory. Subjects:Male Wistar rats (200–300 g). Intervention:Rats received either saline or lipopolysaccharide (10 mg/kg, intraperitoneal) 6 or 24 hours before the experiments. The effects of vasopressin on isolated aortic rings, cardiac function, mean arterial pressure, and both the renal vascular perfusion pressure of perfused kidneys in vitro and renal blood flow in situ were evaluated. The role of Rho-kinase in the renal and systemic effects of vasopressin was investigated through administration of the selective inhibitor Y-27632 and Western blot analysis. Measurements and Main Results:The effect of vasopressin on mean arterial pressure was unaltered and that on renal vascular perfusion pressure enhanced in endotoxemic rats at both 6 and 24 hours after lipopolysaccharide, despite reduced contractile responses in aortic rings and the lack of effect on cardiac function. Vasopressin (3, 10, and 30 pmol/kg, IV) produced increased reduction in renal blood flow in endotoxemic rats. In perfused kidneys from lipopolysaccharide groups, administration of Y-27632 reverted the hyperreactivity to vasopressin. Treatment with Y-27632 partially inhibited the effects of vasopressin on mean arterial pressure and significantly reduced the effects of vasopressin on renal blood flow in control but not in endotoxemic rats. Although the protein levels of Rho-A and Rho-kinase I and II had not been impaired, the levels of phosphorylated myosin phosphatase–targeting subunit 1, the regulatory subunit of myosin phosphatase that is inhibited by Rho-kinase, were increased in both the renal cortex and the renal medulla of endotoxemic rats. Conclusion:Our data suggest that activation of Rho-kinase potentiates the vascular effects of vasopressin in the kidneys, contributing to the maintenance of the hypertensive effects of this agent during septic shock.

Effects of Angiotensin-Converting Enzyme Inhibitor Derived from Tropaeolum majus L. in Rat Preimplantation Embryos: Evidence for the Dehydroepiandrosterone and Estradiol Role

Although several studies have shown the inhibitory effects of Tropaeolum majus extracts (HETM) on angiotensin-converting enzyme (ACE) activity, no studies have been carried out during the beginning of pregnancy, when humoral and hormonal imbalance may affect zygote and early embryo transport. This study investigates whether HETM can affect embryonic development when administered during the one-cell-blastocyst period. Pregnant Wistar rats received orally the HETM (3, 30, and 300 mg/kg/day) from the 1st to the 7th gestational day. Rats were killed on the 8th day of pregnancy and the following parameters were evaluated: clinical symptoms of toxicity (including organ weights), number of corpora lutea, implants per group, preimplantation losses ratio, and the serum levels of dehydroepiandrosterone (DHEA), estradiol, and progesterone. No clinical symptoms of maternal toxicity were evidenced. On the 8th day of pregnancy, the levels of DHEA and estradiol were increased and significant preimplantation losses were observed at all doses used. The present study reveals that the HETM can raise levels of DHEA and estradiol and induce difficulty in the embryo implantation in the early stages of pregnancy. The data contributes significantly to the safety aspects of using this natural product when trying to get pregnant or during pregnancy.

Cellular and Molecular Mechanisms of Diuretic Plants: An Overview

Heart failure, hypertension, cirrhosis and nephritic syndrome are among conditions that alter volume and composition of body fluids and are modulated by diuretics. Natural products are important source of diuretics and have been considered remarkable alternative with greater effectiveness and fewer side effects. However, many of these plants used in traditional medicine must be scientifically assessed about their efficacy and toxicity. Despite the large number of published articles claiming that plants or plant-derived components may act as diuretic agents, few studies have addressed the mechanism of action of medicinal plants. Thus, the aim of this review was to provide an overview of the current knowledge about the major cellular and molecular mechanisms of diuretic plants and/or their main compounds. Many well-established mechanisms (water channels, renal carriers, nitric oxide-cGMP and prostaglandin-cAMP pathways, renin-angiotensin and kinin-kallikrein systems, carbonic anhydrase, and osmotic effects), along with other newly identified targets, are connected to the diuretic activity of many natural products. However, the central path responsible for the activity of these agents remains unclear. Further studies may help clarifying the central role of each of these pathways in the pleiotropic response of these agents.

Atheroprotective effects of Cuphea carthagenensis (Jacq.) J. F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet

ETHNOPHARMACOLOGICAL RELEVANCE Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). MATERIAL AND METHODS Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. RESULTS CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. CONCLUSIONS This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis.

Amides from Piper as a Diuretic: Behind the Ethnopharmacological Uses of Piper glabratum Kunth

Several species of the genus Piper are known in Brazilian folk medicine as having diuretic activity. So, we propose to investigate the acute diuretic activity and the possible toxic effects of Piper glabratum Kunth, popularly known as false Jaborandi. Additionally, we propose to check whether there is any correlation between the biological activities of the crude extract (MEPG) and its 2-methoxy-4,5-methylenedioxy-trans-cinnamoyl-pyrrolidine (MMCP) in Wistar rats. The MEPG was fractioned by chromatography column and the MMCP was identified by analyses of 1H and 13C RMN spectral data and correlations. Both MEPG and MMCP were assayed for diuretic activity. The preparations obtained were orally administered in a single dose to rats. The urine excretion, pH, density, conductivity, and content of Na+, K+, Cl−, and HCO3 − were measured in the urine of saline-loaded animals. Additionally, acute toxicity of the extract was also evaluated. MMCP at doses of 30 mg/kg was able to increase the urine volume, pH, and HCO3 − excretion. Moreover, high dosage of MEPG showed important liver toxicity and elevated mortality when injected intraperitoneally. The results indicate that the MMCP shows important diuretic properties when administered in Wistar rats. Additionally, MEPG can induce important acute toxicity if given in high doses.

Ethnopharmacological approaches to kidney disease-prospecting an indigenous species from Brazilian Pantanal

ETHNOPHARMACOLOGICAL RELEVANCE Although Luehea divaricata Mart. (Malvaceae) is popularly used by the population of the Brazilian Pantanal for the treatment of different types of kidney diseases, no study has been carried out to prove this ethnobotanical indication. AIM To investigate the possible cardiorenal effects of an herbal preparation obtained from L. divaricata leaves. MATERIALS AND METHODS First, to provide quality control standards, a detailed morphological and microchemical characterization of L. divaricata leaves was performed. Then, the purified aqueous extract was obtained from the leaves of this species (ESLD) and a thorough phytochemical characterization was performed. Subsequently, acute oral toxicity test was performed after single administration of different doses (5, 50, 300, 2000mg/kg) in male and female Wistar rats. Finally, the diuretic, hypotensive and antioxidant properties of ESLD (30, 100, 300mg/kg) were evaluated after acute and prolonged treatment and the role of angiotensin converting enzyme, aldosterone, vasopressin, and nitric oxide in these effects was investigated. RESULTS Analyses performed by liquid chromatography-mass spectrometry showed that the main secondary metabolites present in ESLD were flavonol O-glycosides and flavone C-glycosides. Acute and prolonged treatment with ESLD was able to expressively increase urinary volume and electrolyte excretion. Mean blood pressure and systolic blood pressure were also significantly reduced after acute treatment. Moreover, treatment with ESLD was able to reduce thiobarbituric acid reactive species and increase serum nitrate levels. CONCLUSION The data obtained showed that ESLD has an important diuretic and hypotensive effect, which is probably dependent on the reduction of oxidative stress and increased bioavailability of nitric oxide.

Fetopathies associated with exposure to angiotensin converting enzyme inhibitor from Tropaeolum majus L.

Abstract The prevalence of the use of herbal medicines is on the rise across the world, especially amongst pregnant women. A fact that draws attention is that many species commonly used by pregnant women, including the Tropaeolum majus L. (Tropaeolaceae), also present inhibitory activity on the angiotensin-converting enzyme (ACE). Herein, we have investigated the effects of T. majus extract (HETM) on fetal development, evaluating its relationship with possible ACE inhibitory activity. Pregnant Wistar rats were treated with different HETM doses (3, 30 and 300 mg/kg/day) from gestational days 8–20. Rats were sacrificed on the day 20 of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights, maternal ACE activity and aldosterone levels, live fetuses mean; dead fetuses percentage, fetus weight, and fetal malformation. All pregnant rats treated with high HETM doses showed significant reduction in plasma ACE activity accompanied by a decrease in serum aldosterone levels. Moreover, significant changes in fetal development were observed, including growth retardation and renal damage after 20 days of gestation. Thus, data presented demonstrate the significant effects of the use of HETM on fetal development during pregnancy.