Bioactive compounds with antifungal activity against pathogens isolated from pregnant woman: Gallesia integrifolia (garlic wood) is a promising treatment for vulvovaginal candidiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves, bark, and roots of Gallesia integrifolia are consumed in folk medicine through infusion, decoction, and topical preparation by crushing because of its pharmacological properties in several peripheral system disorders, including microbial infections. The presence of various molecules in different parts of the plant likely confers this species' fungicidal action, but scientific evidence is lacking. Vulvovaginal candidiasis mainly affects women of reproductive age. When left untreated, it can cause pregnancy complications. Currently available antifungals often cause undesirable side effects. New alternative therapeutic strategies based on medicinal plants have been proposed. AIM: To investigate the antifungal activity of G. integrifolia against vulvovaginal candidiasis secretion in pregnant women. MATERIALS AND METHODS: Antifungal activity was determined by the minimum inhibitory concentration (MIC), determined by broth microdilution method using Candida spp (NEWP1210), C. albicans (CCCD-CC001), C. tropicalis (CCCD-CC002) standard and clinical isolates from pregnant women with vulvovaginal candidiasis. Nystatin and fluconazole were used as positive controls. The chemical composition of essential oils that were extracted from leaves, flowers, and fruits of G. integrifolia was determined by gas chromatography coupled to mass spectrometry. Reverse docking was used to suggest a possible target in Candida. Conventional docking was used to identify the most probable compound that inhibits fungal growth. RESULTS: A total of 24 compounds were identified, accounting for ∼99% of volatile constituents in the essential oils. Leaves of G. integrifolia contained 3,5-dithiahexanol-5,5-dioxide (40.93%), flowers contained methionine ethyl ester (46.78%), and fruits contained 2,8-dithianonane (54.01%) as the most abundant compounds. The MICs of essential oils of leaves, flowers, and fruits of G. integrifolia against standard strains of Candida spp, C. albicans, and C. tropicalis ranged from 13.01 to 625.00 µg/mL. The essential oil of flowers more effectively inhibited Candida spp. Essential oils of leaves and flowers were similar to fluconazole against C. albicans. Essential oils of flowers and fruits were similar to fluconazole against C. tropocalis. In Candida yeast species that were isolated from vaginal secretion samples from pregnant patients, the MICs of leaves and flowers ranged from 52.08 to 5000.00 µg/mL. The essential oil of leaves (277.77 µg/mL) was the most active against C. albicans. No significant differences were found between the essential oils of leaves and flowers against C. glabrata. Docking simulations suggested that phytol in leaves and flowers was responsible for the antimicrobial effect. CONCLUSION: The present results suggest the potential therapeutic use of G. integrifolia, especially its leaves and flowers, against Candida and vulvovaginal candidiasis.

Croton urucurana Baill. Ameliorates Metabolic Associated Fatty Liver Disease in Rats.

Background: Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. Croton urucurana Baill. (Euphorbiaceae) is a medicinal species, that is, widely distributed in Brazil. It is used in popular medicine to treat gastrointestinal, cardiovascular, and endocrine system diseases. However, its hepatoprotective and lipid-lowering effects have not yet been scientifically investigated. Aim of the study: The present study investigated the effects of an extract of C. urucurana in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia. Material and Methods: The phytochemical composition of C. urucurana was evaluated by liquid chromatography-mass spectrometry. Spontaneously hypertensive 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 [C-] group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (two standard reference drugs that are commonly used to treat dyslipidemia and hypertension, respectively). One group of rats that were not exposed to these risk factors was also evaluated (basal group). Blood was collected for the analysis of cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. The liver and feces were collected for lipid quantification. The liver was also processed for antioxidant and histopathological analysis. Results: The main constituents of the C. urucurana extract were flavonoids, glycosides, and alkaloids. The model successfully induced MAFLD, reflected by increases in AST and ALT levels, and induced oxidative stress in the C- group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, C. urucurana reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the C. urucurana extract (300 mg/kg). Conclusion: C. urucurana extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Pet dogs as reservoir of oxacillin and vancomycin-resistant Staphylococcus spp.

The aim of this study was to verify the bacterial resistance profile and detect the presence of mecA gene in Staphylococcus spp. isolated from the nasal microbiota of domiciled dogs. For this purpose 100 nasal swabs from 100 domiciled dogs were collected from the central area of the city of Umuarama (PR), along with a questionnaire answered by their owners. After the isolation all Staphylococcus spp. isolates were submitted to the diffusion disc test by the Kirby-Bauer method, and only oxacillin-resistant samples were submitted to the PCR technique to search for the mecA gene and the results were then submitted to statistical analysis to verify possible risk variables. The 100 Staphylococcus spp. and coagulase negative, among which 41 isolates were resistant to oxacillin, no samples were positive for the mecA gene presence, however, 12 resistant to vancomycin were found. It can be concluded that the domiciled dogs are carriers of Staphylococcus spp. multiresistant, being these a possible source of human contamination.

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.

Three-Dimensional Cell Cultures as a Research Platform in Lung Diseases and COVID-19.

BACKGROUND: Chronic respiratory diseases (CRD) are a major public health problem worldwide. In the current epidemiological context, CRD have received much interest when considering their correlation with greater susceptibility to SARS-Cov-2 and severe disease (COVID-19). Increasingly more studies have investigated pathophysiological interactions between CRD and COVID-19. AREA COVERED: Animal experimentation has decisively contributed to advancing our knowledge of CRD. Considering the increase in ethical restrictions in animal experimentation, researchers must focus on new experimental alternatives. Two-dimensional (2D) cell cultures have complemented animal models and significantly contributed to advancing research in the life sciences. However, 2D cell cultures have several limitations in studies of cellular interactions. Three-dimensional (3D) cell cultures represent a new and robust platform for studying complex biological processes and are a promising alternative in regenerative and translational medicine. EXPERT OPINION: Three-dimensional cell cultures are obtained by combining several types of cells in integrated and self-organized systems in a 3D structure. These 3D cell culture systems represent an efficient methodological approach in studies of pathophysiology and lung therapy. More recently, complex 3D culture systems, such as lung-on-a-chip, seek to mimic the physiology of a lung in vivo through a microsystem that simulates alveolar-capillary interactions and exposure to air. The present review introduces and discusses 3D lung cultures as robust platforms for studies of the pathophysiology of CRD and COVID-19 and the mechanisms that underlie interactions between CRD and COVID-19.

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.

Verificação da interferência do solvente propilenoglicol sobre o efeito da própolis na produção de lagartas de Bombyx mori L. (Lepidoptera: bombicidae) comparado ao extrato alcoólico de própolis / Interference of propyleneglycol solvent on the effect of propolis in the production of silkworm Bombyx mori L. (Lepidoptera: bombicidae) compared to propolis alcoholic extract / Verificación de la interferencia del solvente propilenoglicol sobre el efecto de propóleos en la producción de gusano de seda Bombyx mori L. (lepidoptera: bombicidae) comparado al extracto alcohólico de propóleos

Este experimento foi realizado no Laboratório de Sericicultura, no Campus Sede da Universidade Paranaense (UNIPAR) de Umuarama, no período de fevereiro a outubro de 2011, com o objetivo de verificar o efeito da própolis em diferentes dosagens na alimentação durante o desenvolvimento biológico do bicho-da-seda (Bombxy mori L.). O método empregado na parte experimental foi a pulverização do extrato glicólico de própolis, diluído em 500mL de água destilada nas folhas de amoreira, nas seguintes dosagens, água-controle, 25mL, 30mL, 35mL e 40mL compondo os tratamentos: controle, T1 , T2 , T3 e T4 respectivamente. As folhas de amoreira foram fornecidas cinco vezes ao dia, durante o manejo alimentar. Verificou-se, pelos resultados obtidos, que as diferentes dosagens de própolis utilizadas não interferiram no ganho de peso das lagartas, no peso dos casulos verdes, no peso da casca sérica e crisálidas, quando comparado ao tratamento controle, mas quando se compara o Controle e T4 do ensaio da primavera, respectivamente, para os teores de seda bruto e líquido, há resultados significativos. Portanto, verificou-se que o extrato glicólico de própolis, em dosagens de 40mL, pode prejudicar o teor líquido de seda em uma produção de casulos, trazendo resultados pouco apreciados dentro da sericicultura...

This experiment was performed at the Laboratory of Sericulture, at the main campus of University Paranaense (UNIPAR), in the city of Umuarama, from February to October 2011, in order to verify the effect of different doses of propolis in feeding during the biological development of silkworm (Bombyx mori L.). The method used in the experiment was the spraying of propolis glycolic extract dissolved in 500-mL distilled water on the mulberry leaves in the following water- -control dosages: 25mL, 30mL, 35mL and 40mL related to the treatment controls T1, T2, T3 and T4, respectively. Mulberry leaves were provided five times a day for feeding management. The results obtained showed that the different dosages of propolis used did not affect the weight gain of the larvae, the weight of green cocoons, shells and pupae when compared to the control treatment. However, when comparing the control and T4 from the Spring assay, respectively, to the levels of crude and net silk, significant results were noted. Thus, it can be concluded that propolis glycolic extract in 40-ml dosages may impair the net silk content in a cocoon production, presenting negative results in sericulture...

: Este experimento se llevó a cabo en el Laboratorio de Sericultura, Campus Sede de la Universidad Paranaense (UNIPAR) de Umuarama, en el período de febrero a octubre de 2011, con el fin de verificar el efecto de propóleos en diferentes concentraciones en la alimentación durante el desarrollo biológico del gusano de seda (Bombyx mori L.). El método utilizado en el experimento fue la pulverización de extracto glicólico de propóleos, disuelto en 500 ml de agua destilada en las hojas de morera, en las siguientes dosis, agua control, 25 mL, 30mL, 35 mL, y 40 mL componiendo los tratamientos: control T1 , T2 , T3 e T4 respectivamente. A las hojas de morera se les han dado cinco veces al día, durante el manejo alimentar. Se verificó, por los resultados obtenidos, que las diferentes dosis de propóleos utilizados no afectaron en la ganancia de peso de los gusanos, en el peso de los capullos verdes, en el peso de la cáscara sérica y crisálidas, en comparación con el tratamiento de control, pero cuando se compara el Control y T4 del ensayo de la primavera, respectivamente, para los niveles de seda cruda y líquida, hay resultados significativos. Por lo tanto, se encontró que el extracto glicólico de propóleos, en dosis de 40 mL, puede perjudicar la concentración líquida de seda en una producción de capullos, trayendo resultados poco apreciados dentro de la sericultura...