Emerson Luiz Botelho Lourenço

Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: Evidence for the inhibition of angiotensin converting enzyme

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 (10-300 mg/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 (0.5-4 mg/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 90 min 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.

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.

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.

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

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.

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.

Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm.