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.

Safety assessment of MEFAS: an innovative hybrid salt of mefloquine and artesunate for malaria treatment.

Malaria is a global public health problem that causes approximately 445 000 deaths annually worldwide, especially in underdeveloped countries. Because of the high prevalence and mortality of the disease, new and less toxic therapeutic agents need to be developed, such as MEFAS, a low-cost hybrid salt that consists of artesunate and mefloquine. However, the efficacy of MEFAS has been systematically demonstrated, its safety requires further investigation. This study investigated the acute toxicity of MEFAS and its precursors, artesunate, and mefloquine. A total of 42 female Swiss mice were divided into seven groups (n = 6/group) that were treated orally by gavage with vehicle (filtered water, negative control), MEFAS (50, 500, and 1000 mg/kg), and 1:1 concentrations of artesunate + mefloquine (50, 500, and 1000 mg/kg). Clinical signs of toxicity were observed for 14 d after treatment. On day 15, the animals were weighed, deeply anesthetized with isoflurane, and euthanized for subsequent collection of the liver, spleen, and kidneys. The relative organ weights were determined, followed by histopathological analysis. Artesunate + mefloquine produced toxic effects compared with the negative control group, reflected by changes in clinical signs, relative organ weights, and histopathological alterations. In MEFAS-treated animals, no changes were observed compared with the negative control group. These findings demonstrate that MEFAS is safer than artesunate + mefloquine after acute administration in mice.

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.

Heart-Protective Effects of Echinodorus grandiflorus in Rabbits That Are Fed a High-cholesterol Diet.

Excess weight and dyslipidemia are among the most serious health problems in Western societies. These conditions enhance the risk of cardiac disease and have been linked with a higher prevalence of cardiac arrhythmias and sudden death. The present study investigated the cardioprotective effects of Echinodorus grandiflorus on ventricular remodeling in rabbits that were fed a 1% cholesterol-rich diet. We first obtained an ethanol-soluble fraction of E. grandiflorus and performed a detailed phytochemical study by liquid chromatography-DAD/ESI-MS. For 60 days, male rabbits were fed the cholesterol-rich diet or a diet without the addition of cholesterol. After 30 days, different groups of rabbits were treated with the ethanol-soluble fraction of E. grandiflorus (10, 30, and 100 mg/kg, p. o.), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. At the end of 60 days, the serum lipoprotein ratio, electrocardiographic profile, histopathological alterations, and the cardiac antioxidant defense system were investigated. Echocardiographic analysis showed morphological and functional alterations in cholesterol-rich diet-fed animals, indicating left ventricle hypertrophy. The total cholesterol/high-density lipoprotein ratio and low-density lipoprotein/high-density lipoprotein ratio were significantly higher in cholesterol-rich diet-fed rabbits. Myocardial flaccidity, fatty degeneration, and concentric left ventricular hypertrophy were observed. An increase in lipid peroxidation levels, a decrease in superoxide dismutase activity, and a decrease in reduced glutathione levels were observed in the myocardium of all cholesterol-rich diet-fed rabbits. Treatment with the ethanol-soluble fraction of E. grandiflorus, especially the highest dose, significantly reduced all of these alterations, thus demonstrating the cardioprotective effect of the ethanol-soluble fraction of E. grandiflorus on cardiac changes that are induced by a cholesterol-rich diet.

Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice.

Toxoplasmosis is a zoonosis of worldwide distribution. Currently, two drugs, pyrimethamine and sulfadiazine, are used as a reference in the treatment of toxoplasmosis, but the resistance of Toxoplasma gondii appears as a relevant public health problem. In order to identify new drugs to toxoplasmosis treatment, we performed a molecular docking of raltitrexed to T. gondii thymidylate synthase-dihydrofolate reductase (TS-DHFR) and also evaluated its efficacy in infected mice. Initially, raltitrexed was docked on the crystallographic structures of TS-DHFR from T. gondii and Mus musculus. Then, 48 h after infection with the T. gondii RH strain, different groups of mice received an oral dose of raltitrexed (0.15, 0.75, and 1.5 mg kg-1). Two days after treatments, raltitrexed was able to prevent mortality and reduce the number of tachyzoites in the peritoneal fluid and liver imprints from infected mice. The results showed that raltitrexed has important protective activities against the T. gondii RH strain. Molecular docking still suggests that the effects against the parasite may be dependent on the inhibition of T. gondii thymidylate synthase. This study opens new perspectives for the use of raltitrexed in patients infected with T. gondii, especially when conventional treatments do not exhibit the expected efficacy.

Effects of extracts from Echinacea purpurea (L) MOENCH on mice infected with different strains of Toxoplasma gondii.

In recent years, due to the growing concern about recurrent epidemics by Toxoplasma gondii and other pathogens in Brazil, there has been an increase in the use of different preparations obtained from Echinacea purpurea in order to test their effectiveness against these infections. Although studies have suggested the beneficial effects of this species against the influenza virus, no data are available on the use of E. purpurea aqueous extract in T. gondii infections. Thus, the aim of this study was to analyze the effect of its administration in Swiss mice submitted to acute and prolonged infection with different T. gondii strains. This study showed that E. purpurea extract induced a significant reduction in the number of tachyzoites in the peritoneal fluid and liver imprints from mice infected by the RH strain. Moreover, prolonged treatment significantly increased the number of brain cysts of animals infected with ME 49 strain. The results obtained in this study suggest that the crude extract obtained from E. purpurea has important protective activities against infection with different T. gondii strains.

Ateroprotective effects of Plinia cauliflora in. New Zealand rabbits: beyond the lipid-lowering effect.

Introduction: Plinia cauliflora [Mart.] Kausel (Myrtaceae), popularly known as "jabuticaba," is a fruit species native to Brazil. Despite extensive widespread usage, its antiatherosclerotic properties' impact remains unknown. Thus, the present study aimed to investigate the cardioprotective effects of a preparation obtained from the fruit peels of P. cauliflora (EEPC). Methods: Male New Zealand rabbits received a 1% cholesterol-supplemented diet for 60 days. On the thirtieth day, the animals were divided into five experimental groups and received, once a day, by the oral route, the EEPC (10, 30, and 100 mg/kg), simvastatin (2.5 mg/kg), or vehicle for 30 days. At the end of the experimental period, peripheral blood and arterial branch samples were collected. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), malondialdehyde (MDA), nitrotyrosine (NT), nitrite, interleukin 1 beta (IL-1b), interleukin 6 (IL-6), soluble inter-cellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were measured. Moreover, the catalase and superoxide dismutase levels were measured on the arterial samples. Histopathological analysis and arterial morphometry were also performed. Results and discussion: The oral administration of ESEG significantly lowered the levels of lipids in rabbits that were fed a CRD diet. This treatment also adjusted the protective system against oxidation in the arteries by decreasing the oxidation of lipids and proteins. Additionally, the levels of IL-1b, IL-6, sICAM-1, and sVCAM-1 in the bloodstream decreased significantly, and this was accompanied by a reduction of atherosclerotic lesions in all branches of the arteries. The findings suggest that EEPC may be a possible option for additional management of atherosclerosis.

Exploring antioxidant and α-glucosidase inhibition in Eugenia L. extracts: a comprehensive phytochemical study.

This study analysed extracts obtained from the leaves of Eugenia uniflora, E. involucrata, and E. myrcianthes to determine their chemical composition, antioxidative properties, and α-glucosidase inhibitory capacity. By using liquid chromatography with a diode array detector, we identified chlorogenic acids, flavonoids, tannins, proanthocyanidins, saponins, and triterpenes in the extracts. The antioxidant activities of the extracts were found to be directly related to their total phenolic, flavonoid content and enzyme inhibition. The E. uniflora aqueous extract showed significant inhibition of α-glucosidase (IC50 0.98 µg mL-1), indicating its potential as a non-competitive inhibitor for managing Diabetes Mellitus. This study contributes to the existing knowledge on the chemical and biological aspects of Eugenia genus.

Natural Products as Modulators of Mitochondrial Dysfunctions Associated with Cardiovascular Diseases: Advances and Opportunities.

The mitochondria have an important role in modulating cell cycle progression, cell survival, and apoptosis. In the adult heart, the cardiac mitochondria have a unique spatial arrangement and occupy nearly one-third the volume of a cardiomyocyte, being highly efficient for converting the products of glucose or fatty acid metabolism into adenosine triphosphate (ATP). In cardiomyocytes, the decline of mitochondrial function reduces ATP generation and increases the production of reactive oxygen species, which generates impaired heart function. This is because mitochondria play a key role in maintaining cytosolic calcium concentration and modulation of muscle contraction, as ATP is required to dissociate actin from myosin. Beyond that, mitochondria have a significant role in cardiomyocyte apoptosis because it is evident that patients who have cardiovascular diseases (CVDs) have increased mitochondrial DNA damage to the heart and aorta. Many studies have shown that natural products have mitochondria-modulating effects in cardiac diseases, determining them as potential candidates for new medicines. This review outlines the leading plant secondary metabolites and natural compounds derived from microorganisms as modulators of mitochondrial dysfunctions associated with CVDs.

Extraction Methods, Chemical Characterization, and In Vitro Biological Activities of Plinia cauliflora (Mart.) Kausel Peels.

Plinia cauliflora (Mart.) Kausel, popularly known as jabuticaba, possesses bioactive compounds such as flavonoids, tannins, and phenolic acids, known for their antioxidant, antibacterial, wound healing, and cardioprotective effects. Therefore, this study aimed to standardize the P. cauliflora fruit peel extraction method, maximize phenolic constituents, and evaluate their antioxidative and antimicrobial effects. Various extraction methods, including vortex extraction with and without precipitation at 25, 40, and 80 °C, and infusion extraction with and without precipitation, were performed using a completely randomized design. Extraction without precipitation (E - P) showed the highest yield (57.9%). However, the precipitated extraction (E + P) method displayed a yield of 45.9%, higher levels of phenolic derivatives, and enhanced antioxidant capacity. Major compounds, such as D-psicose, D-glucose, and citric acid, were identified through gas chromatography-mass spectrometry (GC-MS) analysis. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis identified citric acid, hexose, flavonoids, tannins, and quercetin as the major compounds in the extracts. Furthermore, the extracts exhibited inhibitory effects against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli bacteria. In conclusion, the E + P method efficiently obtained extracts with high content of bioactive compounds showing antioxidant and antimicrobial capacities with potential application as a dietary supplement.

Self-Curing Glass Ionomer Cement Covered by Photopolymerizable Adhesive for Protection of Mucoperiosteal or Gingival Flap Sutures in Canine Oral Surgery.

Periodontal disease is one of the main affections of the oral cavity of dogs. Its main complication is the formation of periapical abscess, which, when affecting the maxillary canine teeth, can lead to the formation of oronasal fistulae. The objective of this study was to evaluate the efficiency of self-curing glass ionomer cement, covered by photopolymerizable adhesive, as a protective element for mucoperiosteal or gingival flap sutures in oral surgery of dogs. We studied 15 dogs from the clinical routine of the dental service of a teaching veterinary hospital, which needed oral surgeries to correct oronasal fistulae, defects or oral cavity communications, regardless of the causal agent. Group one (G1) was composed of seven animals that presented oronasal fistulae after the extraction of maxillary canine teeth compromised by severe periodontal disease. These fistulae were reduced by the double-mucoperiosteal-flap technique, 15 days after the dental extraction. Group two (G2) was composed of five other dogs that presented oronasal fistulae after the extraction of maxillary canine teeth compromised by severe periodontal disease. In this group, the fistulae were reduced by the single-flap technique, immediately after the dental extraction. Group three (G3) was composed of three animals, two of which presented oronasal fistulae due to maxillary fracture and the third one after excision of oral neoplasia. In all groups, simple interrupted sutures were used with 3.0 nylon, and a thin layer of self-curing glass ionomer cement was applied immediately over the operated area. After cement's settling time, a thin layer of photopolymerizable adhesive was applied to the already polymerized cement. In G1, the protective cement was removed on average at 15 (±2) postoperative days, in G2 at 6 (±1) days and in G3 at 11 (±9) days. In the postoperative period, the animals received antibiotics and anti-inflammatory drugs, and they received their usual dry dog food diet. No Elizabethan collar or any other protective measure was used for suturing or the surgical wound. The result was healing of 100% of the oronasal fistulae, without suture dehiscence or the need for new surgical interventions. Thus, it was concluded that the use of self-curing glass ionomer cement covered by photopolymerizable adhesive was fully satisfactory, providing protection of sutures and surgical wounds and showing the potential for routine use in oral surgery in dogs.

Bacopa monnieri in Patients with Parkinson's Disease: A Pilot Study.

Bacopa monnieri (L.) Wettst. could be of interest in the control of symptoms of Parkinson's disease, but clinical evidence of its efficacy is lacking. This clinical trial assessed the effects of an extract of B. monnieri on parameters that are related to Parkinson's diseases. Twenty volunteers with Parkinson's disease were recruited for a primary, interventional, controlled, parallel, double-blind clinical study. The volunteers were assigned to treatment with either a commercial B. monnieri extract (225 or 450 mg/day) or placebo. The Parkinson's Disease Quality-of-Life (PDQL) questionnaire was applied, and motor activity was assessed before treatment and 30, 60, and 90 days after treatment with the B. monnieri extract or placebo. Characteristics such as age, body weight, and height were also collected. No differences in parkinsonian and systemic symptoms, emotional function, or social function were observed between. The delta percent (Δ%) showed time-dependent improvements in emotional function with B. monnieri treatment at the daily dose of 450 mg. A strong correlation was found between quality of life and motor outcomes at baseline and 30 days of treatment with B. monnieri, and a moderate correlation for 60 and 90 days of treatment with B. monnieri when compared with baseline time. A moderate correlation was found between motor outcomes and Hoehn and Yahr stages at baseline. Our results suggest that B. monnieri extract can improve emotional function in Parkinson's disease patients, but further clinical trials are needed to confirm this possibility.

Evidence of the Cardioprotective Effects of Aloysia polystachya in Isoproterenol-Induced Myocardial Infarction in Rats.

Aloysia polystachya is a plant species that is widely used in Brazilian folk medicine for the treatment of different disorders that affect the cardiovascular system. The aim of the study was to investigate the cardioprotective effects of an ethanol-soluble fraction of A. polystachya (ESAP) on isoproterenol-induced myocardial infarction in rats. Different groups of rats (n = 8) were orally treated with ESAP (30, 100, and 300 mg/kg), carvedilol (10 mg/kg), or vehicle (filtered water; 1 mL/100 g) for 7 days. Naive rats received no treatment. On the morning of day 6, acute myocardial infarction was induced by the acute oral administration of isoproterenol (100 mg/kg). On the morning of day 8, all rats underwent electrocardiography and transthoracic echocardiography. Blood samples were then collected, and serum levels of creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) were quantified. ESAP significantly reduced electrocardiographic changes, improved the ventricular ejection fraction, and reduced serum levels of CK-MB and cTNT in infarcted rats. The cardioprotective effects of ESAP could be exploited as an effective tool against isoproterenol-induced myocardial infarction in rats.

Bioprospecting a Film-Forming System Loaded with Eugenia uniflora L. and Tropaeolum majus L. Leaf Extracts for Topical Application in Treating Skin Lesions.

Natural products can be used as complements or as alternatives to synthetic drugs. Eugenia uniflora and Tropaeolum majus are natives of Brazil and have antimicrobial, anti-inflammatory, and antioxidant activities. This study aimed to develop a film-forming system (FFS) loaded with plant extracts with the potential for treating microbial infections. E. uniflora and T. majus leaf extracts were prepared and characterized, and the individual and combined antioxidant and antimicrobial activities were evaluated. The FFS was developed with different concentrations of polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) and analyzed for physicochemical characteristics. The combination of extracts showed a superior antioxidant effect compared to the individual extracts, justifying the use of the blend. FFS prepared with 4.5% PVA, 4.5% PVP, 7.81% E. uniflora extract, and 3.90% T. majus extract was adhesive, lacked scale formation, presented good malleability, and had a suitable pH for topical application. In addition, the viscosity at rest was satisfactory for maintaining stability; water solubility was adequate; skin permeation was low; and the antimicrobial effect was superior to that of the individual extracts. Therefore, the developed FFS is promising for the differentiated treatment of skin lesions through topical application.

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.

Safety Investigations of Two Formulations for Vaginal Use Obtained from Eugenia uniflora L. Leaves in Female Rats.

Medicinal plants have great prominence in research into the development of new medicines. Eugenia uniflora L. (Myrtaceae) is an edible and medicinal plant with economic value in the northeast region of Brazil. Several preparations from E. uniflora leaves and its fruits are employed as a source of nutrients and bioactive compounds. In this study we evaluated the preclinical toxicology of crude extract and vaginal gel obtained from the leaves of E. uniflora (5%, 10%, and 15%) aiming to provide safety for its use in the treatment of vulvovaginitis. Both formulations were applied to the vaginal cavity for 14 days. Detailed observations of the vaginal region, including pruritus, swelling, irritation, burning, pain, and vaginal secretion, as well as the estrous cycle were evaluated. On the fifth day, blood samples were obtained from the supraorbital plexus for biochemical and hematological analyses. The animals were subsequently euthanized. All animals underwent necropsy and macroscopic examination of the vaginal mucosa and reproductive system. A histological examination was also performed. No clinically significant changes were detected during the entire experimental period. All biochemical, hematological, or histopathological parameters were within the normal range for the species. The data obtained allow us to suggest that the E. uniflora vaginal formulations are safe in this experimental model.

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.

Therapeutic Feasibility of the Natural Products in the Heart Complaints: An Overview.

Heart pain is the most frequent complaint leading patients to seek medical help. Functional heart symptoms, especially chest pain, are prevalent and, according to the International Classification of Diseases (ICD-10), are described as "somatoform autonomous functional disorders of the cardiovascular system." The problem lies in the fact that pain does not always have a somatic background, that is, it may be related to crucial underlying heart disease. The population does not know how to differentiate somatic pain from significant ischemic symptoms, and based on the patient's complaints, traditional medicine ends up treating other underlying cardiac diseases. Many unsuccessful unconventional therapies have been proposed in recent years, including herbal medicines that seek to disrupt the disease's pathogenesis. The present review summarizes research carried out in the last 5 years on natural products' heart complaints, including myocardial ischemia, arrhythmia, and heart failure. Several herbal medicines may be used as a replacement or complementary treatment strategy. A total of 17 medicinal plants have shown promising results in preclinical studies. However, human clinical trials are scarce; only two have been presented. Generally, the data are bland, and many issues have been raised about herbal therapies' safety, efficacy, and mode of action. Besides, relevant clinical trials, future perspectives, and possible clinical applications are discussed.

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.

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.