Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A. polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A. polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A. polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A. polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A. polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

Cardioprotective effects of Baccharis trimera (Less) DC in a rodent model of hookah, alcohol, and energy drink exposure / Efectos cardioprotectores de Baccharis trimera (Less) DC en un modelo de roedor de exposición a narguile, alcohol y bebidas energéticas

This study proposes an unpreceded model of cardiovascular disease by combining alcohol and energy drink intake with hookah smoking to investigate the cardiovascular effects of Baccharis trimera (Less.) DC., a medicinal plant used to treat dyslipidemia. For 10 weeks, Wistar rats (n=8) received alcohol (10% ad libitum) and energy drink (2 mL/kg) and/or were exposed to hookah smoke (1 hour/day). In the last 4 weeks, the animals received daily treatment with vehicle (filtered water) or ethanol soluble fraction of B. trimera (30, 100 and 300 mg/kg). Electrocardiography was performed. Systolic, diastolic, and mean blood pressure, heart rate, and plasmatic cholesterol, triglycerides, urea, creatine, aspartate, and alanine aminotransferase levels were determinate. The heart, aorta, and kidneys were histopathological evaluated. In isolation the risk factors altered all the evaluated parameters and when the risk factors were associated, a synergistic effect was observed. Treatment with B. trimera reversed these cardiovascular changes.

Este estudio propone un modelo sin precedentes de enfermedad cardiovascular mediante la combinación de la ingesta de bebidas energéticas y alcohol con fumar narguile para investigar los efectos cardiovasculares de Baccharis trimera (Less.) DC., una planta utilizada para tratar la dislipidemia. Durante 10 semanas, las ratas Wistar recibieron alcohol (10%) y bebida energética y/o fueron expuestas al humo de narguile. En las últimas 4 semanas, los animales recibieron tratamiento con vehículo, fracción soluble en etanol de B. trimera (30, 100, 300 mg/kg). Se realizó electrocardiografía. Se determinaron los niveles de presión arterial sistólica, diastólica y media, frecuencia cardíaca, colesterol plasmático, triglicéridos, aspartato y alanina aminotransferasa, urea y creatina. El corazón, la aorta y los riñones fueron evaluados histopatológicamente. De forma aislada los factores de riesgo alteraron todos los parámetros evaluados y cuando se asociaron los factores se observó un efecto sinérgico. El tratamiento con B. trimera revirtió estos cardiovasculares cambios.

Cardioprotective Effects of Solidago microglossa DC. in Nicotine-Treated Hypertensive Rats.

Solidago microglossa DC. (Asteraceae), "arnica brasileira," is a Brazilian species popularly used to treat hypertension or renal ailments. This study investigated the cardioprotective effects of standardized S. microglossa extract (EESM) in nicotine-treated spontaneously hypertensive rats (SHRs). Moreover, the molecular mechanisms involved in the cardiovascular effects were also investigated. The acute toxicity was evaluated in female Wistar rats. Afterwards, six-month-old male spontaneously hypertensive rats received the EESM (14, 28, and 56 mg/kg), hydrochlorothiazide (25 mg/kg), and vehicle (filtered water; 0.1 mL/100 g) once daily for 28 days. All treatments were associated with 1.8 mg/kg of nicotine. At the end of the experimental period, the renal function, electrocardiographic profile, blood pressure, ventricular function, biochemical parameter, and mesenteric vascular bed reactivity were evaluated. Relative organ weights and cardiac morphometry were also investigated. Nicotine treatment in 6-month-old SHRs induced a significant reduction in renal function, with reduced urinary volume and lower renal elimination of sodium and creatinine. In addition, serum markers of the redox state and blood pressure levels remained significantly elevated, contributing to changes in vascular reactivity and left ventricular hypertrophy associated with reduced ventricular function. After 28 days of treatment, we found that the highest dose of EESM could mitigate all renal and cardiovascular changes developed by the nicotine-treated hypertensive rats. This study presented EESM as a possible cardioprotective drug that prevents cardiovascular dysfunctions in nicotine-treated hypertensive rats. Our data suggest EESM as a potential adjuvant therapy when cardioprotective effects are required.

Small conductance calcium-activated potassium channels and nitric oxide/cGMP pathway mediate cardioprotective effects of Croton urucurana Baill. In hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana Baill. (Euphorbiaceae), popularly known as 'sangue de dragão' is a Brazilian species widely used in traditional medicine for cardiovascular ailments. AIM: To investigate the cardiovascular effects of the C. urucurana extract in spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: Leaves from C. urucurana were collected and morphoanatomically characterized. The ethanol-soluble fraction (ESCU) was obtained and analyzed by LC-DAD-MS. Using female Wistar rats we investigated the acute toxicity of ESCU. Then, SHRs (six months old) received vehicle, hydrochlorothiazide (25 mg/kg), or ESCU (30, 100, 300 mg/kg) for 28 days. At the beginning and at the end of treatments, urine samples were obtained to assess renal function. At the end of the trial period, the blood pressure, mesenteric vascular beds (MVBs) reactivity, and electrocardiographic profile were evaluated. Serum angiotensin-converting enzyme activity, as well as urea, creatinine, sodium, potassium, nitrite, malondialdehyde, nitrotyrosine, and aldosterone levels were determined. Relative organ weights and histopathological analysis were performed. Finally, the cardiac function on a Langendorff system, as well as the molecular mechanisms involved in the vasodilator effects of ESCU in MVBs were also investigated. RESULTS: The compounds annotated from ESCU by LC-DAD-MS included mainly phenylpropanoid derivatives, alkaloids, O-glycosylated megastigmanes, glycosylated flavonoids, flavan-3-ols, and others, such as quercetin O-deoxyhexosyl-hexoside, magnoflorine, reticuline, and taspine. None of the animals showed any signs of toxicity. Male SHRs treated only with the vehicle showed important cardiovascular changes, including a reduction in renal function, increase in serum oxidative stress, and hemodynamic, electrocardiographic, and morphological changes typical of hypertensive disease. Moreover, parameters of cardiac function, including left ventricular developed pressure, peak rate of contraction, peak rate of relaxation, and the rate pressure product were significantly altered, showing a significant impairment of ventricular function. All ESCU-doses presented a significant cardioprotective effect in SHRs rats. The 28-day treatment normalized the hemodynamic, electrocardiographic, morphological, and renal impairments, as well as reversed the changes in ventricular function induced by hypertension. In MVBs with an intact endothelium, ESCU (0.1, 0.3, and 1 mg) dose-dependently induced vasodilation. Endothelium removal or the inhibition of nitric oxide synthase prevented the vasodilatory effect of ESCU. Perfusion with a physiological saline solution that contained KCl, tetraethylammonium, or apamin also abolished the vasodilatory effect of ESCU. CONCLUSION: Prolonged ESCU-treatment showed significant cardioprotective effects in SHRs. Moreover, the data showed the role of nitric oxide and calcium-activated small conductance potassium channels in the cardiovascular effects of ESCU.

Multiple Risk Factors for Heart Disease: A Challenge to the Ethnopharmacological Use of Croton urucurana Baill.

Croton urucurana Baill. is a native Brazilian tree, popularly known as "sangra-d'água" or "sangue-de-dragão," based on the red resinous sap of the trunk. Its use has been transmitted through generations based on popular tradition that attributes analgesic, anti-inflammatory, and cardioprotective properties to the tree. However, its cardioprotective effects have not yet been scientifically investigated. Thus, the present study investigated the pharmacological response to an ethanol-soluble fraction from the leaves of C. urucurana in Wistar rats exposed to smoking and dyslipidemia, two important cardiovascular risk factors. The extract was evaluated by high-performance liquid chromatography. Wistar rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin (2.5 mg/kg) + enalapril (15 mg/kg). One group of rats that was not exposed to these risk factors was also evaluated (basal group). Electrocardiograms and systolic, diastolic, and mean blood pressure were measured. Blood was collected to measure total cholesterol, triglycerides, urea, and creatinine. The heart and kidneys were collected and processed for oxidative status and histopathological evaluation. The phytochemical analysis revealed different classes of flavonoids and condensed tannins. The model induced dyslipidemia and cardiac and renal oxidative stress and increased levels of urea and creatinine in the negative control group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased cholesterol and triglyceride levels. In contrast to simvastatin + enalapril treatment, the C. urucurana extract exerted cardiac and renal antioxidant effects. No alterations of electrocardiograms, blood pressure, or histopathology were observed between groups. These findings indicate that C. urucurana exerts lipid-lowering, renal, and cardioprotective effects against oxidative stress in a preclinical model of multiple risk factors for heart disease.

Cardioprotective effects of Talinum paniculatum (Jacq.) Gaertn. in doxorubicin-induced cardiotoxicity in hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Talinum paniculatum (Jacq.) Gaertn. (Talinaceae) is a medicinal species that is widely distributed throughout Brazil. Popularly known as "major-gomes," the species is used in folk medicine for the treatment of cardiovascular disorders. AIM OF THE STUDY: To evaluate the effect of an ethanolic extract of T. paniculatum (EETP) in rats with renovascular hypertension and heart failure and determine its chemical composition. MATERIALS AND METHODS: First, EETP was obtained, and its chemical profile was analyzed by LC-DAD-MS. The acute toxicity was evaluated in female Wistar rats. The model of renovascular hypertension was established in male Wistar rats by combining the Goldblatt 2K1C method and intraperitoneal doxorubicin administration for 6 weeks. The animals were then treated daily with EETP (30, 100, and 300 mg/kg) or metoprolol (25 mg/kg) by gavage for 28 days. The negative control group was treated with vehicle (filtered water). The sham group consisted of animals that were not subjected to 2K1C or cardiotoxicity and were treated with vehicle. Renal function was evaluated on days 1, 14, and 28. At the end of treatment, the electrocardiographic profile, blood pressure, and mesenteric vascular reactivity were investigated. Serum urea, creatinine, angiotensin converting enzyme, nitrotyrosine, malondialdehyde, nitrite, aldosterone, and sodium and potassium levels were measured. The heart, aorta artery, liver, and right kidney were collected, weighed, and processed for histopathological analysis. Cardiac chambers also underwent morphometric analysis. RESULTS: No signs of toxicity were observed in female Wistar rats. Thirty-two compounds were annotated from EETP, including flavonoids, chlorogenic acids, and saponins. EETP treatment resulted in a significant cardiorenal-protective response, normalizing electrocardiographic and hemodynamic alterations, and preventing ventricle remodeling. These effects were associated with serum antioxidant activity and angiotensin-converting enzyme (ACE) inhibition. CONCLUSION: The present study demonstrated that EETP may exert cardioprotective effects through serum antioxidant activity and ACE inhibition, preventing alterations of hemodynamic and endothelial function, and reducing damage to cardiac structure. Thus, EETP, especially at the 100 and 300 mg/kg doses, may be useful for preventing doxorubicin-induced cardiotoxicity in hypertensive patients.

Ethnopharmacological investigation of the cardiovascular effects of the ethanol-soluble fraction of Aloysia polystachya (Griseb.) Moldenke leaves in spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloysia polystachya (Griseb) Moldenke (Verbenaceae), popularly known as "burrito", is a South American species widely prescribed by local Brazilian healers for the treatment of cardiovascular diseases. However, its antihypertensive and cardioprotective effects are still unknown. AIM: To evaluate the role of the ethanol-soluble fraction of A. polystachya leaves (ESAP) against hypertension in spontaneously hypertensive rats (SHRs), as well as its safety, morphoanatomical and phytochemical aspects. MATERIALS AND METHODS: First, the leaves and stems of A. polystachya were analyzed by optical and scanning electron microscopy in order to provide anatomical data for quality control. Then, ESAP was obtained and its chemical profile was analyzed by LC-DAD-MS. In addition, the cytotoxic and acute toxicity potential of ESAP were evaluated in six cell lines and in female Wistar rats, respectively. Next, female spontaneously hypertensive rats (SHRs) received ESAP (30, 100, 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. Weekly kidney function was monitored by analyzing urinary parameters. At the end of the 28-day treatment, the electrocardiographic profile, blood pressure, and renal and mesenteric vascular reactivity were evaluated. Relative organ (heart, kidney, and liver) weights and biochemical parameters were also evaluated. Finally, the heart, kidneys, and aorta were collected for determination of the tissue redox state, cardiac morphometry, and histopathological analysis. RESULTS: The chemical profile of ESAP was composed by organic acids, a nucleoside, methoxylated flavones and glycosylated compounds including phenolic acids, phenylpropanoids, iridoids and monoterpenes. No signs of toxicity were observed in all cell's lines nor in female Wistar rats submitted to this trial. All SHRs from the negative control group presented a reduction in renal function, alterations in the renal and mesenteric vascular reactivity, and electrocardiographic and morphometric changes typical of ventricular hypertrophy. Oral prolonged ESAP-administration in SHRs was able to reverse renal, electrocardiographic and hemodynamic changes induced by hypertension. Moreover, ESAP-treatment was able to modulate the vascular and renal arterial reactivity and tissue redox state. The aforementioned data were accompanied by reduction of cardiac hypertrophy. CONCLUSION: In this study, we present important anatomical and phytochemical data that contributed to the correct identification and quality control of A. polystachya. In addition, we have shown that ESAP is safe after acute administration and present significant cardioprotective effects (at 30, 100, and 300 mg/kg doses) in SHRs after prolonged treatment.

Ethnopharmacological investigations of the leaves of Cecropia pachystachya Trécul (Urticaceae): A native Brazilian tree species.

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia pachystachya Trécul (Urticaceae) is a medicinal plant popularly known as 'embaúba'. In Brazil, the leaves of this species are used for the treatment of various kidney and cardiovascular diseases. However, there are no detailed studies on the renal and cardiovascular activities of this species. No studies on the anatomy or the quality control of this herbal drug is available thus far. AIM: This study was aimed to investigate the ethnopharmacological properties of the leaves of C. pachystachya. MATERIAL AND METHODS: The leaves of C. pachystachya were analyzed by light and scanning electron microscopy for pharmacobotanical and anatomical characterization. The ethanol-soluble fraction of C. pachystachya leaf extract (ESCP) was characterized by high-performance liquid chromatograph equipped with diode array detector and mass spectrometry (HPLC-DAD-MS). The acute oral toxicity of ESCP on female Wistar rats was assessed. The acute and prolonged diuresis and antioxidant effects of ESCP (30, 100, and 300 mg/kg) were evaluated in male Wistar rats. In addition, the hypotensive effects of the ESCP as well as the vasodilatory activity in isolated and perfused mesenteric vascular beds were investigated. RESULTS: The anatomical markers obtained in this study can help in the identification of C. pachystachya, as well as to distinguish it from the other 'embaúbas'. The metabolites found in the ESCP were phenolic compounds, mainly C- and O-glycosylated flavonoids. The ESCP did not exhibit any toxic effects at a dose of 2000 mg/kg. Significant diuretic activities were observed at the doses of 30, 100, and 300 mg/kg. In addition, a significant modulating activity of the tissue redox state was observed after prolonged treatment. On the other hand, no hypotensive or vasodilator activity was observed. CONCLUSION: The key findings of the present study can contribute to the taxonomy, species identification and quality control of C. pachystachya. Chemical studies have shown the presence of glycosylated flavonoids, phenylpropanoid derivative and proanthocyanidins. The pharmacological studies showed significant diuretic and antioxidant effects of C. pachystachya leaf extract, indicating a possible validation of its popular medicinal use.

From general toxicology to DNA disruption: A safety assessment of Plinia cauliflora (Mart.) Kausel.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel (Myrtaceae) is popularly known as "jaboticaba" or "jaboticaba". The fruit is appreciated for both fresh consumption and the manufacture of jelly, juice, ice cream, fermented beverages, and liqueurs. The more widespread traditional use of the plant involves the treatment of diarrhea, which utilizes all parts of the plant, including the fruit peels. AIM OF THE STUDY: We sought to elucidate possible risks of the administration of an ethanol-soluble fraction that was obtained from an infusion of P. cauliflora fruit peels (SEIPC). We performed a series of experiments to evaluate possible toxicity, in which we administered SEIPC orally both acutely and repeatedly for 28 days. We also evaluated possible endocrine-disruptive and genotoxic effects in eukaryotic cells. The possible mutagenic activity of SEIPC was evaluated using reverse mutation (Ames) assays. MATERIALS AND METHODS: SEIPC was produced and chemically characterized by LC-DAD-MS. Acute toxicity and behavioral and physiological alterations were evaluated in the modified Irwin test. Respiratory rate, arterial blood gas, electrocardiography, respiratory rate, heart rate, and blood pressure were evaluated, and hematological, biochemical, and histopathological analyses were performed after 28 days of oral treatment. The comet assay, mammalian erythrocyte micronucleus test, uterotrophic test, Hershberger bioassay, and AMES test were performed using appropriate protocols. RESULTS: From SEIPC, ellagic acid and derivatives, flavonols and anthocyanidins, as well as citric acid and gallic acid, were annotated by LC-DAD-MS. We did not observed any significant toxic effects after acute or prolonged SEIPC treatment. No endocrine-disruptive or mutagenic effects were observed. CONCLUSIONS: The present study found that SEIPC did not cause any significant alterations of various corporeal systems, including cardiac electrical activity, body temperature, respiratory rate, and arterial pressure. No alterations of biochemical, hematological, or blood gas parameters were observed. SEIPC did not cause any perturbations of the endocrine system or mutagenic, cytotoxic, or genotoxic effects. These findings substantiate the safe clinical use of P. cauliflora.

Anchietea pyrifolia A. St.-Hil. as a Cardiovascular-Endowed Species: A Whole-Biological Investigation.

Although leaves of Anchietea salutaris are used in Brazilian traditional medicine, there is no available data in the literature proving its efficacy and safety. Thus, the aim of the study was to perform a meticulous botanical, phytochemical, toxicological, and pharmacological investigation of A. salutaris in Wistar rats. At first, a morphoanatomical characterization of Anchietea pyrifolia leaves and stems was performed. Then, a purified infusion (ethanol-soluble fraction obtained from A. pyrifolia [ESAP]) was obtained followed by its chemical profile elucidation. Furthermore, an acute toxicity test was performed, and the acute and prolonged diuretic and hypotensive effects were also evaluated in Wistar rats. Finally, the vasodilatory responses of ESAP in mesenteric vascular beds were investigated. The main secondary metabolites identified from ESAP were O-glycosylated flavonoids, chlorogenic acids, and phenylpropanoic acid derivatives. ESAP did not promote any toxic effects in female rats nor increased urinary excretion in male rats after a single exposure. However, ESAP significantly reduced renal elimination of sodium, potassium, and chloride after prolonged treatment. An ESAP highest dose promoted significant acute hypotension without affecting blood pressure levels after prolonged use. Furthermore, its cardiovascular effects seem to be related with the calcium-activated potassium channel activation in resistance vessels.

Ethnopharmacological approaches to Talinum paniculatum (Jacq.) Gaertn. - Exploring cardiorenal effects from the Brazilian Cerrado.

ETHNOPHARMACOLOGICAL RELEVANCE: Talinum paniculatum (Jacq.) Gaertn. (Talinaceae), popularly known as "major gomes" and "erva gorda", is a non-conventional food plant extensively distributed throughout the Brazilian territory. In Brazilian folk medicine, this species is used as aphrodisiac, to treat gastrointestinal problems, and as a cardioprotective agent. However, there are no reports in the literature proving its cardiovascular effects. AIM: To perform a whole-ethnopharmacological investigation of the cardiorenal properties of the ethanol soluble fraction from T. paniculatum (ESTP) in Wistar rats. MATERIAL AND METHODS: First, plant samples were collected, properly identified and a morpho-anatomical characterization was carried out to provide quality control parameters. Then, ESTP was obtained and its chemical profile was determined by LC-DAD-MS. In addition, an acute toxicity assay was conducted in female Wistar rats in order to observe any toxic effects after one single administration. Finally, the diuretic and hypotensive potential of ESTP (30, 100 and 300 mg/kg) were investigated in male rats followed by the evaluation of its possible effects on peripheral vascular resistance. RESULTS: Chemical compounds identified from ESTP were chlorogenic acids, amino acids, nucleosides, O-glycosylated flavones and organic acids. No signs of toxicity as well as no changes in urine volume or electrolyte elimination were observed after ESTP acute treatment. On the other hand, prolonged treatment with all doses of ESTP significantly increased urine volume and electrolyte excretion (Na+, K+ and Cl-) without affecting blood pressure or heart rate. Apparently, these effects are involved with the activation of the small conductance calcium-activated potassium channels contributing to the increase of renal blood flow and glomerular filtration rate. CONCLUSION: Data presented show important information about the ethnomedicinal properties of T. paniculatum. In addition, the study presents the ESTP as a possible herbal medicine, especially when a sustained diuretic effect is required.

Chemical constituents of Cochlospermum regium (Schrank) Pilg. root and its antioxidant, antidiabetic, antiglycation, and anticholinesterase effects in Wistar rats.

The main physiological consequence of diabetes mellitus is chronic hyperglycemia. This condition is related to the formation of free radicals including advanced glycation end products (AGES) and to an increase in inflammatory processes. Cochlospermum regium (Schrank) Pilg., part of the Bixaceae family, is a cerrado plant known for its anti-inflammatory effects. The objectives of this study were to analyze the constituent compounds of C. regium roots and to evaluate the antioxidant, antiglycation, antidiabetic, and anticholinergic effects of its hydromethanolic extract through in vitro and in vivo experimental models. The presence of phenols, flavonoids, condensed tannins, and flavonols was analyzed by liquid chromatography - photodiode array (LC/PDA) analysis. Whereas antioxidant activity was investigated via DPPH, ABTS, ß-carotene/linoleic acid, and malondialdehyde colorimetric assays. Inhibition of AGEs was examined via a bovine serum albumin system whose glycosylating agent was glucose. Antidiabetic potential was examined in normoglycemic Wistar rats that received glucose overload, in alloxan-induced diabetic rats, and in rats that received a hyperglycemic diet. Disaccharidase inhibition was assessed using in vitro and in vivo methods, as was acetylcholinesterase (AChE) inhibition in brain structures. The hydromethanolic extract (CRHE) possessed a high concentration of phenolic compounds and showed antioxidant effects. The LC-DAD results revealed that CRHE contained a high concentration of phenolic acids and the majority was gallic acid. Treatment with CRHE caused significant inhibition of AGE formation. The oral glucose tolerance test (OGTT) in normoglycemic animals showed a reduction in blood glucose levels after treatment with 100 mg/kg CHRE, accompanied by an increase in hepatic glycogen content. There was also a significant reduction in the fasting glucose levels of alloxan-induced diabetic animals after 7 days of treatment with daily doses of 100 mg/kg. After 14 weeks of hyperglycemic diet, the last four or which were combined with 100 mg/kg CRHE treatment, there was a decrease in blood triglyceride levels. There was also a statistically significant decrease in the enzymatic activity of maltase, lactase and sucrase. The results demonstrate that oral administration of 30 and 100 mg/kg CRHE inhibited AChE activity in different brain structures. Thus, the extract of C. regium showed promising antioxidant, antiglycation, and antidiabetic effects that may be related to its high phenolic content.

Celosia argentea L. (Amaranthaceae) a vasodilator species from the Brazilian Cerrado - An ethnopharmacological report.

ETHNOPHARMACOLOGICAL RELEVANCE: Celosia argentea L. (Amaranthaceae), popularly known as "crista de galo", is used in folk medicine due to its diuretic and hypotensive effects. However, there are no reports in the literature regarding its pharmacological effects on the cardiovascular system as well as no data proving the safety of this species. AIM: To perform a detailed ethnopharmacological investigation of the ethanol soluble fraction from C. argentea (ESCA) using male and female Wistar rats. MATERIAL AND METHODS: Firstly, a morpho-anatomical characterization was performed to determine the quality control parameters for the identification of the species under investigation. Then, the ethanol extract was obtained and chemically characterized by LC-DAD-MS. Furthermore, an oral acute toxicity study was performed in female Wistar rats. Finally, the possible diuretic and hypotensive effects of three different doses of ESCA (30, 100 and 300 mg/kg) were evaluated in male Wistar rats. Besides, the vasodilatory response of ESCA in mesenteric vascular beds (MVBs) and its involvement with nitric oxide/cGMP and prostaglandin/cAMP pathways as well as potassium channels were evaluated. RESULTS: The main secondary metabolites present in ESCA were phenolic compounds, megastigmanes and triterpenoid saponins. ESCA caused no toxic effects in female rats nor increased urinary excretion in male rats after acute administration. However, ESCA significantly increased the renal elimination of potassium and chloride, especially at the end of 24 h after administration. Intermediary dose (100 mg/kg) of ESCA was able to promote significant acute hypotension and bradycardia. Moreover, its cardiovascular effects appear to be involved with the voltage-dependent K+ channels activation in MVBs. CONCLUSION: This study has brought new scientific evidence of preclinical efficacy of C. argentea as a hypotensive agent in normotensive rats. Apparently, these effects are involved with the activation of the voltage-sensitive K+ channels contributing to the reduction of peripheral vascular resistance and cardiac output.

Biological Characterization of an Edible Species from Brazilian Biodiversity: From Pharmacognostic Data to Ethnopharmacological Investigation.

Talisia esculenta (A. St.-Hil.) Radlk. is a large tree belonging to family Sapindaceae and popularly known as "pitombeira" or "pitomba." Although species have relevant economic and medicinal uses in Brazil, no study has investigated its effectiveness as a diuretic, hypotensive, and antihypertensive agent. The aim of this study was to present a detailed anatomical and histochemical study for T. esculenta and provide important safety and efficacy parameters. After morpho-anatomical and microchemical study, a purified aqueous extract (ethanol soluble fraction obtained from T. esculenta [ESTE]) was obtained, and detailed phytochemical investigation was performed. Subsequently, acute oral toxicity test was performed in male and female rats. Moreover, diuretic, hypotensive, and antihypertensive effects on normotensive and spontaneously hypertensive rats (SHR) were investigated. Finally, the effects of prolonged treatment with ESTE on serum levels of nitrite, thiobarbituric acid reactive species, and nitrotyrosine were also measured in SHR. Oral treatment with ESTE did not induce acute toxic effects and did not affect urine production, blood pressure, or heart rate of normotensive and SHR. Prolonged treatment with ESTE was able to increase serum nitrite levels and significantly reduce oxidative and nitrosative stress markers in SHR. Data obtained showed that ESTE has a significant antioxidant activity without showing any clinical signs of acute toxicity. The use of this species as a diuretic, hypotensive, or antihypertensive agent should be carried out with caution, since administration in rodents did not produce renal and/or hemodynamic responses that justify this indication.

Diuretic herb Gomphrena celosioides Mart. (Amaranthaceae) promotes sustained arterial pressure reduction and protection from cardiac remodeling on rats with renovascular hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Gomphrena celosioides Mart., belonging to the Amaranthaceae family, is a weed known as "perpétua," and its ethnopharmacological use is to treat of urinary tract disorders and kidney stones. Urinary tract disorders and kidney stones could include several pathological conditions such hypertension, diuretic and lithiasic problems. In the present work a model of renovascular hypertension was developed in vivo to investigate its usefulness as an antihypertensive drug. AIM OF THE STUDY: Evaluate the effect of acute and 28 day oral administration of G. celosioides extract on systemic arterial pressure and diuresis of renovascular-hypertensive rats, as well as its effect on cardiac remodeling and vascular reactivity. MATERIALS AND METHODS: Ethanolic extract of G. celosioides (EEGC) was used. To induce renovascular hypertension, adult male Wistar rats were submitted to Goldblatt 1K1C or 2K1C surgery. The mean arterial pressure (MAP) of 1K1C animals was directly assessed by cannulation of the carotid artery before and after intraduodenal acute administration of 30, 100 or 300 mg/kg of EEGC. For the 4-week assay, 2K1C animals received daily treatments with water (control group), 100 mg/kg EEGC or 15 mg/kg enalapril for 28 days. Diuresis and caudal blood pressure were assessed weekly, and at the 28th day of treatment, the MAP was directly quantified shortly before euthanasia. Internal organs were removed, weighed and routinely processed for histology and the left ventricle wall was measured. Blood was collected for biochemical analysis and mechanism investigation by quantification of angiotensin converting enzyme (ACE) activity and aldosterone, nitrite and thiobarbituric acid reactive substances (TBARS) concentration. The rats' mesenteric beds were isolated and cannulated to have their pressure variation assessed after crescent doses of phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside (SNP). RESULTS: EEGC acutely reduced MAP the dose of 100 mg/kg. In the 4-week assay, EEGC acted as diuretic after acute administration after 1, 2, 3 and 4 weeks of treatment. EEGC also acted as an antihypertensive and it showed significant difference already after 1 week (and after 3 and 4 weeks) compared to control, with its MAP close to pre-surgery values at the end of the experiment. It promoted ACE inhibition, which led to lower aldosterone levels. The lower TBARS and higher nitrite concentration found in the EEGC group suggest antioxidant activity and NO maintenance. Moreover, EEGC counteracted the impairment of vascular reactivity induced by renovascular hypertension. The extract group presented thinner left ventricle wall compared to the control, meaning reduced hypertension-induced cardiac remodeling. CONCLUSIONS: The G. celosioides diuretic effect is maintained on renovascular hypertensive rats and can reduce the blood pressure after the first week of treatment by inhibiting ACE and these effects are longstanding and strong enough to promote protection against cardiac remodeling. Therefore, it shows potential as an antihypertensive drug.

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.

Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension.

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

Evaluation of embryotoxic and teratogenic effects of the oil extracted from Caryocar brasiliense Cambess pulp in rats.

The objective of this study was to evaluate the maternal, embryotoxic and teratogenic effects of Caryocar brasiliense pulp oil (OPCB), oil widely used in Brazilian cuisine and traditional medicine. Pregnant Wistar female rats were used in this study for three treatment groups (250, 500 and 1000 mg/kg/day) and a control group. The OPCB was administered orally throughout the period of organogenesis of females (6th until the 15th day of gestation). The pregnant females were gross necropsied on d20, followed by maternal and fetus examination, to evaluate the teratogenicity, reproductive and developmental performance of OPCB. The results showed there was no significant statistical difference in the ponderal evolution of the pregnant females, as well as in the behavioral, hematological, biochemical or histopathological data, indicating the absence of maternal toxicity of the oil. The mean number of corpora lutea, implantation and resorption sites, as well as all calculated reproductive rates, also remained statistically similar between the groups, indicating low embryotoxic effects of the tested plant specie. In fetal examination, external anomalies and skeletal abnormalities were observed in all treated and control groups. The NOAEL for maternal toxicity and embryo/fetal development for the OPCB administered by gavage, was 1000 mg/kg/bw/day.

Ethnopharmacological investigations of the cardio-renal properties of a native species from the region of Pantanal, state of Mato Grosso do Sul, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthospermum hispidum DC. is an important medicinal herb that belongs to family Asteraceae, popularly used as a diuretic and hypotensive in the region of Pantanal, state of Mato Grosso do Sul, Brazil. Despite the relevance of this species throughout the country, there are no detailed studies about its possible ethnobotanical indication. AIM: To carry out a detailed ethnopharmacological investigation of the cardio-renal properties of A. hispidum. MATERIALS AND METHODS: First, a detailed morpho-anatomical study with the purpose of characterizing and providing quality control parameters for the species was carried out. Then, purified aqueous extract (ESAH) was obtained and a detailed phytochemical investigation about its main secondary metabolites was performed. In addition, a thorough acute toxicological study was conducted to evaluate the actual toxic effects of this preparation. Finally, the possible diuretic and hypotensive effects of ESAH on male Wistar rats (30, 100, 300mg/kg; intraduodenally) were evaluated, and using pharmacological antagonists or inhibitors, the involvement of prostaglandin/cAMP and nitric oxide/cGMP pathway and potassium channels in ESAH-induced hypotension was investigated. RESULTS: The analyses performed by liquid chromatography-mass spectrometry showed that the main secondary metabolites present in ESAH were phenolic compounds, such as caffeoylquinic acids (chlorogenic acid), dicaffeoylquinic acids and glycosylated flavonoids (quercetin glucoside and galactoside). ESAH did not induce any acute toxic effects and did not affect the urinary volume or renal excretion of electrolytes in Wistar rats. On the other hand, intraduodenal administration of ESAH induces a significant acute hypotensive effect. Previous treatment with N(G)-nitro-L-arginine methyl ester, methylene blue, or tetraethylammonium fully avoided the hypotensive effect of ESAH. All other parameters were not affected by treatment with ESAH. CONCLUSION: Data obtained in this study allow us to suggest that ESAH obtained from A. hispidum presents an important acute hypotensive effect, which appears to be dependent on the nitric oxide/cGMP pathway. This study presents new evidences about the therapeutic potential of this species when acute hypotensive response is required.

Acute and subacute oral toxicity assessment of the oil extracted from Attalea phalerata Mart ex Spreng. pulp fruit in rats.

Attalea phalerata Mart. ex Spreng., popularly known as "bacuri", is a native plant from the brazilian Cerrado and used in folk medicine as a pulmonary decongestant, an anti-inflammatory for joints and antipyretic. There is an expectation about the use in chronic disease of the Attalea phalerata oil since its composition is high in carotenoids and beneficial fatty acids. The aim of the study was to evaluate the toxicological profile of the oil extracted from Attalea phalerata Mart. ex Spreng. pulp (APO). Acute and subacute toxicity studies were performed in male and female Wistar rats according to the OECD - Guidelines 425 and 407. For the acute toxicity, one single dose of the APO (2000mg/kg) was administered by gavage to five female rats. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the APO were administered to male and female rats for 28 consecutive days. No deaths or behavioral changes were observed during both experiments as well as no changes in organ weights, hematological, histopathological parameters. The biochemical parameters showed changes in phosphatase alkaline and albumin levels, however these values are within the normal range for the species. A significant reduction in cholesterol and triglycerides was also observed in some of the animals treated with the APO. Therefore, the LD50 is higher than 2000mg/kg and the APO oil can be considered safe at the doses tested in rats. However, further assessments are required in order to proceed to clinical studies in humans.