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.

From the environment to the hospital: How plants can help to fight bacteria biofilm.

The emergence of resistance to antibiotics has become a global challenge as far as the control and treatment of nosocomial infections are concerned. Compared to the planktonic state, biofilms generally confer more resistance to antibiotics and may become a potential source of infection. Researchers are thus focused on developing novel drugs not as vulnerable as the current ones to bacterial resistance mechanisms and also able to target bacteria in biofilms. Natural products, especially those derived from plant sources, have substantiated significant medicinal activity with unique properties, making them perfect candidates for these much-needed therapeutics. Despite being a vast resource of antimicrobial molecules, limitations, including the low concentration of the extracted active compound and bioavailability, challenge the clinical application of medicinal plants to combat these infections. Nanotechnology through green synthesis is one of the strategies to explore the medicinal potential of plants. Research has established the promising outcome of this method in antibiofilm activity, in addition to improved drug delivery, targeting, and pharmacokinetic profiles. This review summarized the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. We also discussed biotechnological advances in medicinal plants to fight and eradicate biofilm-forming microorganisms.

The NO-cGMP-K+ Channel Pathway Participates in Diuretic and Cardioprotective Effects of Blutaparon portulacoides in Spontaneously Hypertensive Rats.

Blutaparon portulacoides is a Brazilian plant species that is widely used in folk medicine. The present study investigated the role of an aqueous extract of B. portulacoides against hypertension in spontaneously hypertensive rats. The aqueous extract of B. portulacoides was obtained from the whole plant. Its chemical profile was analyzed by ultraperformance liquid chromatography-tandem mass spectrometry. The acute toxicity of the aqueous extract of B. portulacoides was evaluated in female Wistar rats. Male 6-month-old spontaneously hypertensive rats then received the aqueous extract of B. portulacoides (30, 100, and 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. On days 1, 14, and 28, the diuretic effects of the aqueous extract of B. portulacoides were evaluated. The role of prostaglandins and the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway in the diuretic activity of the aqueous extract of B. portulacoides was also investigated. At the end of the treatment, hepatic and renal biochemical markers, serum nitrotyrosine, malondialdehyde, nitrite, and aldosterone levels, and angiotensin-converting enzyme activity were measured. The electrocardiographic profile, blood pressure, and renal vascular reactivity were also assessed. The heart, kidneys, and liver were collected to determine relative organ weight, histopathology, and cardiac morphometry. Caffeic acid, ferulic acid, and several flavonoids were identified in the aqueous extract of B. portulacoides. No signs of toxicity were observed. Prolonged treatment with the aqueous extract of B. portulacoides (300 mg/kg) induced significant diuretic activity by activating the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway. These effects reduced blood pressure and oxidative stress and prevented renal vascular dysfunction and left ventricular hypertrophy that was induced by hypertension. Overall, the present data suggest that the aqueous extract of B. portulacoides has important diuretic and cardioprotective effects by activation of the nitric oxide-cyclic guanosine monophosphate-potassium channel pathway.

Thyroid-disrupting effects of chlorpyrifos in female Wistar rats.

Thousands of chemicals are released into the environment daily, arousing great scientific interest because they can influence the overall function of living organisms. The indiscriminate use of pesticides, especially organophosphate, confers important risks to both public and environmental health. Previous studies showed that chlorpyrifos (CPF) acts as an endocrine disruptor. Nevertheless, CPF is still widely used in many countries. Thus, we evaluated the thyroid-disrupting effects of CPF after short-term low-dose oral exposure in female Wistar rats. A total of 48 female Wistar rats were divided into five experimental groups (n = 8/group) that were treated orally by gavage with vehicle (control) and chlorpyrifos (0.01, 0.1, 1, and 10 mg/kg) for 5 days. Clinical signs of toxicity were observed throughout treatment. On day 6, the animals were weighed. Serum samples were obtained to measure levels of thyroid hormones, alanine aminotransferase, aspartate aminotransferase, bilirubin, glutamyl transpeptidase, and estradiol. The animals were then euthanized by deep anesthesia with isoflurane. The thyroid gland, liver, spleen, and kidneys were collected to determine relative organ weight and perform histopathological analyses. We observed a significant increase in total triiodothyronine (T3) levels in all CPF treatment groups, even at very low doses that corresponded to the Acceptable Daily Intake. Only the highest dose tested significantly increased both total and free T3 levels. In the group that received the highest dose of CPF, thyroid follicles had irregular contours and few or no colloids. The present results indicated that short-term low-dose CPF exposure in female rats induced significant thyroid-disrupting effects.

Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation.

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

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.

Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats.

BACKGROUND: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of atherosclerosis. METHODS: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenic diet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days. Serum lipids oxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1ß and 6, and markers of renal and liver function were measured. Renal function, blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. RESULTS: Prolonged treatment with ESCS induces significant hypolipidemic and antioxidant effects, that prevent endothelial dysfunction and modulated the local inflammatory process, reducing the evolution of the atherosclerotic disease. CONCLUSIONS: This study provides a scientific basis for the popular use of C. spicatus for the treatment of atherosclerosis.

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.

Cuphea calophylla var. mesostemon (Koehne) S.A. Graham: A Whole-Ethnopharmacological Investigation.

Several species of Cuphea are used medicinally and are reported to have cardioprotective, diuretic, and antihypertensive properties. In Brazil, Cuphea species are collectively called "sete-sangrias" due to their similar appearances and are also used interchangeably for the same therapeutic purposes. So the aim of the study was to characterize morphoanatomy of leaves and stems, evaluate the safety, and investigate the diuretic, hypotensive, vasodilatory, and antioxidant properties of ethanol-soluble fraction of Cuphea calophylla var. mesostemon (Koehne) S.A. Graham. Initially, the morphoanatomical characterization of the leaves and stems of C. calophylla var. mesostemon was performed. For the pharmacological evaluation, the ethanol-soluble fraction from Cuphea calophylla (ESCC) was obtained and chemically characterized by high-performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry techniques. Then, acute toxicity, diuretic, hypotensive, antioxidant, and vasodilatory effects were evaluated in Wistar rats. The main chemical compounds identified from ESCC were gallic acid derivatives, ellagitannins, and flavonoids. ESCC showed no acute toxic effect. ESCC showed no acute toxic effect and the estimated median lethal dose (LD50) was above 2000 mg/kg. ESCC treatment (30, 100, and 300 mg/kg) did not present any significant acute diuretic or hypotensive effects. However, an important reduction in the elimination of electrolytes was observed after the acute administration, and a significant increase in renal sodium elimination was observed after 7 days of treatment. In the cardiac tissue, the groups treated with ESCC presented significant increase in superoxide dismutase activity.

Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spicatus (Jacq.) Sw., also known as "cana-do-brejo," is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. AIM: To investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. MATERIALS AND METHODS: C. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. RESULTS: From LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentration-dependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. CONCLUSION: The data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional 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.

Ethnomedicinal Plants Used for the Treatment of Cardiovascular Diseases by Healers in the Southwestern State of Paraná, Brazil, and Their Validation Based on Scientific Pharmacological Data.

Cardiovascular diseases are responsible for high morbidity and mortality rates worldwide. Among treatment options, medicinal plants are frequently used, especially in developing countries, such as Brazil. Despite social development that has been observed in the last decades, the use of medicinal plants is still driven by popular knowledge, especially by healers. The present study sought to identify medicinal species that are used for the treatment of cardiovascular diseases by healers in the microregion of Francisco Beltrão, Paraná, Brazil. The snowball technique was used to select informants, and data were collected through interviews. The research was performed in two stages: (1) a structured interview and (2) the collection and botanical identification of the species that were mentioned by the healers. Medicinal plants were classified into the following categories of cardiovascular agents: hypotensive and antihypertensive agents, lipid-lowering agents, diuretic agents, and cardiotonic agents. To analyze the data, the frequency was determined, Spearman correlations were calculated, and the informant consensus factor (ICF) and use value were obtained. Some characteristics, such as female gender and old age, were associated with knowledge about medicinal plants. Overall, 77 different species and 149 medicinal uses were cited by the healers. With regard to categories of use, the highest number of species was found among lipid-lowering plants, and the highest ICF was found for species that are used as cardiotonics. Moreover, a literature review indicated that among the cited species, several still lack studies that have proven their effects on the cardiovascular system. The traditional use of medicinal plants for the treatment of cardiovascular diseases is broad in the study regions. The present results are important for clarifying popular knowledge in this region and providing a framework for selecting species with potential for the development of new pharmacological studies.

Baccharis trimera (Less.) DC: An Innovative Cardioprotective Herbal Medicine Against Multiple Risk Factors for Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and among its modifiable risk factors are dyslipidemia, diabetes, and smoking. Experimental models evaluated this risk factors singly, however, there is a lack of models that agglomerate these risk factors, resembling real patients and elucidating the pathophysiology of CVD. Moreover, few studies have investigated the cardioprotective effects of Baccharis trimera, a species with lipid-lowering effects. In this study, ethanol-soluble fraction of B. trimera was characterized by liquid chromatography-mass spectrometry. Diabetes was induced by streptozotocin in Wistar rats that also received 0.5% cholesterol-enriched chow and were exposed to the smoke of nine cigarettes, 5 days/week, for 4 weeks. During the last 2 weeks, the animals were treated with vehicle (C-), B. trimera, or simvastatin plus insulin. At the end, cholesterol, triglyceride, urea, and creatinine levels; blood pressure (BP); heart rate (HR); abdominal aortic morphometry; vascular reactivity; renal and cardiac oxidative status; and histopathological changes were evaluated. The agglomerate of risk factors promoted alterations contrary to those described in the literature for the isolated risk factors. The C- group exhibited oxidative stress, increase in biochemical parameters, and thickening of the wall of the abdominal aorta. HR, systolic, diastolic, and mean BP decreased, and vascular reactivity was altered. Cardiac and renal histopathological changes were observed. Treatment with B. trimera reversed these changes and this effect may be partially attributable to lipid-lowering action and to the inhibition of free radical generation. B. trimera has cardioprotective effects in this model, with no toxicity.

Development of a Predictive Model to Induce Atherogenesis and Hepato-Renal Impairment in Female Rats.

Therapeutic approaches for the treatment of dyslipidemia and atherosclerosis have radically changed in recent decades. Part of this advance undeniably stems from basic biomedical research that has provided a better understanding and identification of new therapeutic targets. The aim of this work was to develop a model to induce atherogenesis and hepato-renal impairment in female Wistar rats. The following groups received the respective treatments for 60 days: control animals, non-ovariectomized rats that received an atherogenic diet (NEAD), ovariectomized rats that received an atherogenic diet (NOAD), non-ovariectomized rats that received an atherogenic diet and oral Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; LEAD), and ovariectomized rats that received an atherogenic diet and oral l-NAME (LOAD). Animals in the NEAD, NOAD, LEAD, and LOAD groups also received methimazole and cholecalciferol daily. Urinary, biochemical, hemodynamic, and electrocardiographic parameters and renal function were assessed. Samples of the liver, heart, kidney, and arteries were collected to investigate redox status and perform histopathological analyses. All of the groups developed dyslipidemia and hepatic steatosis. Only the NEAD group developed arterial lesions that were compatible with fatty streaks. Renal function was significantly impaired in the LEAD and NOAD groups. These results indicate a viable alternative to induce atherogenesis and hepato-renal impairment in female rats.

Pharmacological safety of Plinia cauliflora (Mart.) Kausel in rabbits.

Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.

Antiatherosclerotic Properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli: From Antioxidant and Lipid-Lowering Effects to an Anti-Inflammatory Role.

Echinodorus grandiflorus is an important medicinal plant species that is native to South America. Despite extensive popular usage as a hypolipidemic drug, its effects as an atheroprotective agent remain unknown. The aim of this study was to evaluate the effects of an ethanol-soluble fraction that was obtained from E. grandiflorus (ESEG) leaves against the development of atherosclerosis in rabbits. Male rabbits received a diet that was supplemented with 1% cholesterol (cholesterol-rich diet [CRD]) for 60 days. After 30 days of the CRD, the animals were divided into five groups (n = 6) and treated with ESEG (10, 30, and 100 mg/kg), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. The negative control group was fed a cholesterol-free diet and treated orally with vehicle. At the end of 60 days, serum lipids, oxidized low-density lipoprotein, thiobarbituric acid reactive substances, nitrotyrosine, and serum interleukin 1 beta (IL-1ß), IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were determined. Samples from the aortic arch and thoracic segment were also collected to investigate the tissue antioxidant defense system and perform histopathological analysis. Oral ESEG administration significantly reduced serum lipid levels in CRD-fed rabbits. This treatment also modulated the arterial antioxidant defense system by reducing lipid and protein oxidation. Similarly, serum IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels significantly decreased, accompanied by a reduction of atherosclerotic lesions in all arterial branches. These findings suggest that ESEG may be a new herbal medicine that can be directly applied for the treatment and prevention of atherosclerotic disease.

Cardioprotective effects of Plinia cauliflora (Mart.) Kausel in a rabbit model of doxorubicin-induced heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, the fruit of a native species that is popularly known as "jabuticaba" (Plinia cauliflora [Mart.] Kausel) is widely consumed fresh or used for the production of liqueur, juice, and jelly. In Brazilian folk medicine, this species is used to treat asthma, throat inflammation, and gastrointestinal and cardiovascular disturbances. However, no previous studies have reported its cardioprotective effects. AIM: To evaluate the possible cardioprotective effects of a hydroethanolic extract of Plinia cauliflora (EEPC) in female rabbits in a model of doxorubicin-induced heart failure. MATERIAL AND METHODS: EEPC was obtained and fractionated by solid phase extraction, and its constituents were determined by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Thirty female New Zealand rabbits received doxorubicin administration for 6 weeks to induce heart failure. EEPC was orally administered at doses of 75 and 150 mg/kg daily for 42 days. Enalapril (5 mg/kg) was used as a reference cardioprotective drug. At the end of the experimental period, blood pressure and heart rate were recorded. Serum parameters, including lipid profile, troponin, creatinine, nitrotyrosine, malondialdehyde, nitrite, and brain natriuretic peptide, were measured. The electrocardiographic profile and renal vascular reactivity were evaluated. Cardiac histopathology and ventricular morphometry were performed, and the tissue enzymatic antioxidant system was investigated. RESULTS: A total of 37 compounds were detected in EEPC, including organic acids, phenolic acid derivatives, flavonoids, anthocyanins, and hydrolysable tannins (gallotannins and ellagitannins). EEPC treatment induced a cardiorenal protective response, prevented hemodynamic and functional alterations, and prevented ventricle remodeling. These effects were associated with the normalization of creatinine and brain natriuretic peptide levels and modulation of the tecidual antioxidant defense system. CONCLUSION: The present study demonstrated that EEPC may prevent doxorubicin-induced heart failure by modulating the antioxidant defense system, reducing reactive oxygen species-induced damage, preventing alterations of hemodynamic and endothelial function, and preventing damage to the cardiac structure. EEPC, especially at the highest dose tested, may be considered a cardioprotective coadjuvant to prevent doxorubicin-induced cardiotoxicity.

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.