RESUMO
Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC50) of 4.59 µg/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 µm (without TCE), 3.07 µm with 0.5% and 3.23 µm with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 °C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin.
Assuntos
Preparações de Ação Retardada/química , Emulsões/química , Meliaceae/química , Animais , Antioxidantes/química , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Tamanho da Partícula , Permeabilidade , Óleos de Plantas/química , Óleo de Brassica napus , Reologia , Pele/metabolismo , Absorção Cutânea , Suínos , Água/químicaRESUMO
Helicobacter pylori is a bacterium that is present in the stomach of about 50% of the global population and is associated with several gastric disorders, including cancer. Natural products with antimicrobial activity have been tested against H. pylori, among them Trichilia catigua (catuaba), which is widely distributed in Brazil. This study aimed to evaluate extracts of T. catigua bark against H. pylori via determination of the minimum inhibitory and bactericidal concentrations (MIC and MBC); evaluation of virulence factors by real-time PCR, synergism with standard antimicrobials and morphology by scanning electron microscopy and simulations of the mechanism of action by molecular docking. The ethyl acetate fraction provided the best results, with an MIC50 of 250 µg/mL and a 42.34% reduction in urease activity, along with reduced expression of the CagA and VacA genes, which encode for the main virulence factors. This fraction presented synergistic activity with clarithromycin, reducing the MIC of the drug by four-fold. Docking simulations suggested that the extracts inhibit fatty acid synthesis by the FAS-II system, causing damage to the cell membrane. Therefore, T. catigua extracts have potential as an adjuvant to treatment and are promising for the development of new anti-H. pylori drugs.
Assuntos
Antibacterianos , Proteínas de Bactérias , Helicobacter pylori , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Casca de Planta , Extratos Vegetais , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Casca de Planta/química , Brasil , Fatores de Virulência , Meliaceae/química , Claritromicina/farmacologia , Urease , Sinergismo Farmacológico , Antígenos de BactériasRESUMO
Periodontitis is clinically characterized by destruction of the tooth support system and tooth loss. Porphyromonas gingivalis (Pg) plays a dominant role in periodontitis. Fractions and isolated compounds from an acetone-water extract of the roots of Limonium brasiliense (Lb) were tested in vitro for their anti-adhesive capacity against Pg on human KB buccal cells, influence on gingipains, the main virulence factors of Pg, and biofilm formation. Fractions EAF and FLB7 (50 µg/mL) reduced the bacterial adhesion of Pg to KB cells significantly (63 resp. 70%). The proanthocyanidin samarangenin A inhibited the adhesion (72%, 30 µM), samarangenin B (71%, 20 µM), and the flavan-3-ol epigallocatechin-3-O-gallate (79%, 30 µM). Fraction AQF, representing hydrophilic compounds, reduced the proteolytic activity of Arginin-specific gingipain (IC50 12.78 µg/mL). Fractions EAF and FLB7, characterized by lipohilic constituents, inhibited Arg-gingipain (IC50 3 µg/mL). On Lysine-specific gingipain, AQF has an IC50 15.89, EAF 14.15, and FLB7 6 µg/mL. The reduced bacterial adhesion is due to a strong interaction of proanthocyanidins with gingipains. AQF, EAF, and FLB7 significantly inhibited biofilm formation: IC50 11.34 (AQF), 11.66 (EAF), and 12.09 µg/mL (FLB7). In silico analysis indicated, that the polyphenols act against specific targets of Pg, not affecting mammalian cells. Therefore, Lb might be effective for prevention of periodontal disease by influencing virulence factors of Pg.
Assuntos
Adesinas Bacterianas , Aderência Bacteriana , Biofilmes , Cisteína Endopeptidases , Cisteína Endopeptidases Gingipaínas , Extratos Vegetais , Plumbaginaceae , Porphyromonas gingivalis , Fatores de Virulência , Biofilmes/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Humanos , Adesinas Bacterianas/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Plumbaginaceae/química , Raízes de Plantas/química , Proantocianidinas/farmacologia , Proantocianidinas/isolamento & purificação , Células KB , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Trichilia catigua A. Juss (Meliaceae) is used in Brazilian folk medicine to alleviate fatigue and emotional stress and improve memory. Previous studies from our laboratory reported that an ethyl-acetate fraction (EAF) of T. catigua that was given before cerebral ischemia in vivo prevented memory loss and reduced oxidative stress and neuroinflammation. Despite the value of these findings of a neuroprotective effect of T. catigua, treatment that was given immediately before or immediately after ischemia limits its clinical relevance. Thus, unknown is whether T. catigua possesses a specific time window of efficacy (TWE) when administered postischemia. AIM OF THE STUDY: Given continuity to previous studies, we investigated whether an EAF of T. catigua maintains its neuroprotective properties if treatment begins at different time windows of efficacy after ischemia. We also evaluated, for the first time, whether T. catigua possesses neuroplasticity/neurotrophic properties. MATERIAL AND METHODS: Rats were subjected to transient global brain ischemia (TGCI) and then given a single dose of the EAF (400 mg/kg) or vehicle (1 ml/kg) orally 1, 4, or 6 h postischemia. The levels of protein PCG, GSH, and GSSG, and activity of SOD and CAT were assayed as markers of oxidative stress on the day after ischemia. In another experiment, naive rats underwent spatial learning training in a radial maze task and then subjected to TGCI. Delayed treatment with the EAF began 4 or 6 h later and continued for 7 days. Retrograde memory performance was assessed 10, 17, and 24 days postischemia. Afterward, brains were examined for neurodegeneration and neuronal dendritic morphology in the hippocampus and cerebral cortex. Another group received the EAF at 4 h of reperfusion, and 4 days later their brains were examined for GFAP and Iba-1 immunoreactivity. Lastly, ischemic rats received the EAF 4 h after ischemia and neural plasticity-related proteins, BDNF, SYN, PSD 95, and NeuN were measured in the hippocampus 7 and 14 days after ischemia. RESULTS: A single EAF administration 1, 4, or 6 h postischemia alleviated oxidative stress that was caused by ischemia, expressed as a reduction of the amount of the PCG and GSSG, normalization of the GSH/GSSG ratio, and the restoration of SOD activity. Ischemia caused the persistent loss of memory (i.e., amnesia), an outcome that was consistently ameliorated by treatment with the EAF that was initiated 4 or 6 h postischemia. The 4 h delay in EAF treatment positively impacted dendritic morphology in neurons that survived ischemia. TGCI reduced BDNF, SYN, PSD-95, and NeuN protein levels in the hippocampus and cerebral cortex. The EAF normalized SYN and PSD-95 protein levels. Ischemia-induced neurodegeneration and glial cell activation were not prevented by EAF treatment. CONCLUSION: The present study corroborates prior data that demonstrated the neuroprotective potential of T. catigua and extends these data by showing that the delayed administration of EAF postischemia effectively prevented memory impairment and decreased oxidative stress, dendritic deterioration, and synaptic protein loss within a TWE that ranged from 1 to 6 h. This specific TWE in preclinical research may have clinical relevance by suggesting the possible utility of this plant for the development of neuroprotective strategies in the setting of ischemic brain diseases. Another innovative finding of the present study was the possible neurotrophic/neuroplastic properties of T. catigua.
Assuntos
Isquemia Encefálica , Meliaceae , Fármacos Neuroprotetores , Ratos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dissulfeto de Glutationa/metabolismo , Dissulfeto de Glutationa/farmacologia , Dissulfeto de Glutationa/uso terapêutico , Extratos Vegetais/farmacologia , Isquemia Encefálica/tratamento farmacológico , Estresse Oxidativo , Infarto Cerebral/tratamento farmacológico , Hipocampo , Transtornos da Memória/tratamento farmacológico , Acetatos/farmacologia , Superóxido Dismutase/metabolismo , Plasticidade Neuronal , Fármacos Neuroprotetores/farmacologiaRESUMO
A previous optimization of supercritical extraction from guarana seeds was performed applying orthogonal array design (OA9(34)). The antioxidant and antimicrobial activities of these extracts, as well as metabolomic profiling and correlations from the compounds by statistical analysis were determined. Extracts 1 (40% ethanol; 20 min; 40 °C and 100 bar), 2 (40% methanol; 60 min; 40 °C and 200 bar), and 8 (40% methanol; 40 min; 60 °C and 100 bar) had the highest combined values of antioxidant capacity for the DPPH, FRAP, ABTS and xanthine oxidase system methods, and were identified by chemometric analysis. Similar chemical profiles of the extracts were obtained by LC-DAD-MS, and were identified: methyl-xanthine, (epi)catechin and dimers and trimers of type A and B proanthocyanidins. The heat map analysis showed positive correlation between antioxidant methods DPPH, FRAP and ABTS and with flavan-3-ols and proanthocyanidins. Extract 3 was active against Gram-negative and -positive bacteria and Candida tropicalis.
RESUMO
Paullinia cupana Kunth, commonly known as guarana, is a native Brazilian plant species from the Amazon area that presents various biological effects, including antimicrobial action. The aim of this study was to chemically analyse the semipurified aqueous extract (AqF) of the plant and to evaluate the activity of crude (CE), ethyl-acetate (EAF), and AqF extracts against Helicobacter pylori. The chemical profile of AqF was determined based on solid analysis 13C-NMR, direct infusion mass spectrometry (ESI-MS), and MALDI-TOF. The 13C-NMR spectrum showed characteristics of flavan-3-ol and oligomeric proanthocyanidins. ESI-MS revealed the presence of procyanidin, caffeic acid and its derivatives. MALDI-TOF analysis detected procyanidins of up to 6 units and profisetinidins of up to 5 units. Whereas CE and EAF showed inhibitory activity against H. pylori, CE, EAF, and AqF presented not high inhibitory activity against urease. The results demonstrate the potential of P. cupana to control and prevent H. pylori infection.
Assuntos
Helicobacter pylori/efeitos dos fármacos , Paullinia/química , Extratos Vegetais/química , Antioxidantes/farmacologia , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Infecções por Helicobacter/prevenção & controle , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Urease/antagonistas & inibidoresRESUMO
Poincianella pluviosa has already been described as capable of healing skin wounds. In an attempt to prolong contact of the drug with the wound, it was proposed in this study to evaluate wound healing using a crude extract (CE) of P. pluviosa incorporated in carboxymethylcellulose polymer films. The chromatographic profile of the semipurified fraction of P. pluviosa was evaluated by ultra-high performance liquid chromatography (UHPLC), confirming the compounds gallic acid, geraniin, and ellagic acid. The films were evaluated for their physical and mechanical properties, water vapor permeability, moisture absorption capacity, and FTIR spectroscopy. For in vivo experiments, wounds were made on the back of rats and treated daily for 4, 7, 10, or 14 days with film containing CE or control film. At the end of each period, skin permeation analysis and histological analysis were made using re-epithelialisation, cell proliferation, and collagen formation. Statistical significance was determined by GraphPad Prism using t test and Mann-Whitney test. Anti-staphylococcal activity was evaluated with standard strains of Staphylococcus aureus, methicillin-resistant, and coagulase negative. It was demonstrated that the presence of CE in the films increased the capacity to absorb water and decreased resistance and permeability. The CE of the film permeated the skin, reaching the dermis and was able to influence re-epithelisation, cell proliferation, and collagen formation. Satisfactory results were observed against S. aureus strains, particularly coagulase negative. Films with CE of P. pluviosa can be an alternative in the wound healing, protecting against opportunistic infections and giving comfort to the patient.
Assuntos
Antibacterianos/farmacologia , Fabaceae/química , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Casca de Planta/química , Polímeros , Ratos , Pele/efeitos dos fármacos , Pele/lesões , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
Alzheimer's disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aß) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia, Limonium brasiliense, Paullinia cupana, Poincianella pluviosa, Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aß25-35 toxicity in SH-SY5Y cells. The effect of the EAF of S. adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 (S. adstringens, P. pluviosa and L. brasiliense) protected SH-SY5Y cells from Aß25-35-induced toxicity. The EAF of S. adstringens at 15.62 µg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aß25-35-induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S. adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aß25-35, which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa and S. adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Linhagem Celular Tumoral , Citoproteção/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Polifenóis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
O Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae), chamado popularmente de baicuru ou guaicuru é uma erva perene presente em todo litoral sul do Brasil, sendo indicada tradicionalmente para síndrome pré-menstrual e distúrbios menstruais. Essas atividades são atribuídas à presença dos polifenóis concentrados em seus rizomas, que também apresentam atividades bacteriostáticas, antioxidantes, antivirais e anti-inflamatórias. No desenvolvimento de formulações feitas a partir da droga vegetal são necessários testes de controle de qualidade durante todo o processo a fim de garantir a segurança, eficácia e qualidade da matéria-prima até sua formulação final. As metodologias utilizadas no desenvolvimento deste trabalho foram de análises físico-químicas para o controle de qualidade, análises quantitativas para determinação do teor de polifenóis totais e, por fim, uma análise comparativa entre os resultados obtidos no ano da coleta do material vegetal (2010) e das mesmas características após 13 anos da coleta, utilizando amostras do L. brasiliense com a presença de fungos ou sem nos rizomas. Sendo assim, este trabalho teve como objetivo realizar o controle de qualidade comparativo dos rizomas de Limonium brasiliense coletados em 2010 em relação ao teor de polifenóis totais e de umidade em 2023. Os resultados obtidos evidenciaram a produção de polifenóis pelos fungos na amostra contaminada, além de mostrarem a qualidade de armazenagem da droga vegetal. Com isso, foi possível concluir que o teor de polifenóis totais da amostra com fungo aumentou após 13 anos da coleta, e que neste interim não houve mudanças no teor de umidade da amostra sem fungo, garantindo sua qualidade no desenvolvimento de formulações ou pesquisas futuras.
Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae), popularly called baicuru or guaicuru, is a perennial herb present throughout the southern coast of Brazil, traditionally indicated for premenstrual syndrome and menstrual disorders. These activities are attributed to the presence of polyphenols concentrated in its rhizomes, which also have bacteriostatic, antioxidant, antiviral and anti-inflammatory activities. When developing formulations made from plant-based drugs, quality control tests are necessary throughout the process to ensure the safety, efficacy and quality of the raw material until its final formulation. The methodologies used in the development of this work were physical-chemical analyzes for quality control, quantitative analyzes to determine the total polyphenol content and, finally, a comparative analysis between the results obtained in the year the plant material was collected (2010) and the same characteristics after 13 years of collection, using samples of L. brasiliense with or without the presence of fungi in the rhizomes. Therefore, this work aimed to carry out comparative quality control of Limonium brasiliense rhizomes collected in 2010 in relation to the content of total polyphenols and moisture in 2023. The results obtained showed the production of polyphenols by fungi in the contaminated sample, in addition to show the storage quality of the plant drug. With this, it was possible to conclude that the total polyphenol content of the sample with fungus increased after 13 years of collection, and that in the meantime there were no changes in the moisture content of the sample without fungus, guaranteeing its quality in the development of formulations or future research.
Limonium brasiliense (Boiss.) Kuntze (Plumbaginaceae), popularmente llamada baicuru o guaicuru, es una hierba perenne presente en toda la costa sur de Brasil, tradicionalmente indicada para el síndrome premenstrual y trastornos menstruales. Estas actividades se atribuyen a la presencia de polifenoles concentrados en sus rizomas, que también tienen actividades bacteriostáticas, antioxidantes, antivirales y antiinflamatorias. Cuando se desarrollan formulaciones elaboradas a partir de medicamentos de origen vegetal, son necesarios ensayos de control de calidad durante todo el proceso para garantizar la seguridad, eficacia y calidad de la materia prima hasta su formulación final. Las metodologías utilizadas en el desarrollo de este trabajo fueron análisis físico- químicos para control de calidad, análisis cuantitativos para determinar el contenido de polifenoles totales y, finalmente, un análisis comparativo entre los resultados obtenidos en el año de recolección del material vegetal (2010) y el mismas características después de 13 años de colecta, utilizando muestras de L. brasiliense con o sin presencia de hongos en los rizomas. Por lo tanto, este trabajo tuvo como objetivo realizar un control de calidad comparativo de los rizomas de Limonium brasiliense recolectados en 2010 en relación al contenido de polifenoles totales y humedad en 2023. Los resultados obtenidos mostraron la producción de polifenoles por hongos en la muestra contaminada, además de mostrar la calidad de almacenamiento de la droga vegetal. Con esto se pudo concluir que el contenido total de polifenoles de la muestra con hongos aumentó después de 13 años de colecta, y que mientras tanto no hubo cambios en el contenido de humedad de la muestra sin hongos, garantizando su calidad en el desarrollo. de formulaciones o investigaciones futuras.
RESUMO
Abstract Aims: To identify the histopathological alterations in organs of Wistar rats to evaluate toxic effects of use of Annonamuricata Raw Leaf Extract (AMRLE) alone or in association with DMBA. Settings and Design: Sixty female Wistar rats were used, separated into groups and treated with a single dose of 65 mg/kg of DMBA and/or with 50; 100 and 200 mg/kg of AMRLE. Hematoxylin-Eosin (HE) and 1% methylene blue stains were used in the histopathological analysis and quantification of Aberrant Crypts (ACs) and Aberrant Crypt Focus (ACF). Fischer and Kruskal Wallis tests were used in the statistical analysis. Results: The administration of 65 mg/kg of DMBA and/or 50, 100 and 200 mg/kg of AMRLE did not influence weight development. Some histopathological alterations (hepatic steatosis; inflammatory foci in the liver, kidney and lung; pulmonary lymphoid hyperplasia, ectasia and hyperplasia in mammary gland epithelium) and the development of ACs and ACF in the intestinal colon were observed in all groups, except in the group negative control, with no statistical difference between analysed groups. Conclusions: Histopathological alterations and the formation of ACs and ACF did not show a statistically significant difference between the groups analysed. However, although AMRLE has antioxidant effects due to the presence of phenolic components, there was still the formation of some pathological processes that may be related to the isolated toxic action of DMBA and/or associated with other components of AMRLE, since these changes were not seen in the negative control group.
Resumen Objetivos: Identificar las alteraciones histopatológicas en órganos de ratas Wistar para evaluar los efectos tóxicos del uso del Extracto de Hoja Cruda de Annona muricata (AMRLE) solo o en asociación con DMBA. Configuración y diseño: Se utilizaron sesenta ratas hembras Wistar, se separaron en grupos y se trataron con una dosis única de 65 mg/kg de DMBA y/o con 50, 100 y 200 mg/kg de AMRLE. Se utilizaron tinciones de hematoxilina-eosina (HE) y azul de metileno al 1% en el análisis histopatológico y la cuantificación de criptas aberrantes (CA) y focus de criptas aberrantes (FCA). En el análisis estadístico se utilizaron las pruebas de Fischer y Kruskal Wallis. Resultados: La administración de 65 mg/kg de DMBA y/o 50, 100 y 200 mg/kg de AMRLE no influyó en el desarrollo del peso. Se observaron algunas alteraciones histopatológicas (esteatosis hepática; focus inflamatórios en el hígado, riñón y pulmón; hiperplasia, ectasia en epitelio de la glándula mamaria e hiperplasia linfoide pulmonar) y el desarrollo de CA y FCA en el colon intestinal en todos los grupos, excepto en el grupo control negativo, sin diferencias estadísticas entre los grupos analizados. Conclusiones: Las alteraciones histopatológicas y la formación de CA y FCA no mostraron diferencias estadísticamente significativas entre los grupos analizados. Sin embargo, aunque AMRLE tiene efectos antioxidantes debido a la presencia de componentes fenólicos, aún existe la formación de algunos procesos patológicos que pueden estar relacionados con la acción tóxica aislada del DMBA y/o asociados con otros componentes de AMRLE, ya que estos cambios no fueron observados en el grupo control negativo.
Assuntos
Animais , Ratos , Annona/efeitos adversos , Annona/toxicidade , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Extratos Vegetais/toxicidade , Ratos WistarRESUMO
Abstract The therapeutic drugs to treat Herpes simplex virus (HSV) infections have toxic side effects and there has been an emergence of drug-resistant strains. Therefore, the search for new treatments for HSV infections is mounting. In the present study, semi-solid formulations containing a crude hydroethanolic extract (CHE) from Schinus terebinthifolia were developed. Skin irritation, cutaneous permeation, and in vivo therapeutic efficacy of the formulations were investigated. Treatment with the ointment formulations did not result in any signs of skin irritation while the emulsions increased the thickness of the epidermis in Swiss mice. The cutaneous permeation test indicated that the CHE incorporated in the formulations permeated through the skin layers and was present in the epidermis and dermis even 3 h after topical application. In vivo antiviral activity in BALB/c mice treated with the CHE ointments was better than those treated with the CHE emulsions and did not significantly differ from an acyclovir-treated group. Taken together, this suggests that the incorporation of CHE in the ointment may be a potential candidate for the alternative topical treatment of herpetic lesions.
Assuntos
Preparações Farmacêuticas/análise , Simplexvirus/classificação , Herpesvirus Humano 1/classificação , Anacardiaceae/efeitos adversos , Antivirais/efeitos adversos , Aciclovir/antagonistas & inibidores , Eficácia , Emulsões/efeitos adversosRESUMO
Wound healing is a complex process that involves several biological events, and a delay in this process may cause economic and social problems for the patient. The search continues for new alternative treatments to aid healing, including the use of herbal medicines. Members of the genus Caesalpinia are used in traditional medicine to treat wounds. The related species Poincianella pluviosa (DC.) L.P. Queiroz increases the cell viability of keratinocytes and fibroblasts and stimulates the proliferation of keratinocytes in vitro. The crude extract (CE) from bark of P. pluviosa was evaluated in the wound-healing process in vivo, to validate the traditional use and the in vitro activity. Standardized CE was incorporated into a gel and applied on cutaneous wounds (TCEG) and compared with the formulation without CE (Control) for 4, 7, 10, or 14 days of treatment. The effects of the CE on wound re-epithelialization; cell proliferation; permeation, using photoacoustic spectroscopy (PAS); and proteins, including vascular endothelial growth factor (VEGF), superoxide dismutase 2 (SOD-2) and cyclooxygenase 2 (COX-2) were evaluated. The TCEG stimulated the migration of keratinocytes at day 4 and proliferation on the following days, with a high concentration of cells in metaphase at 7 days. Type I collagen formed more rapidly in the TCEG. PAS showed that the CE had permeated through the skin. TCEG stimulated VEGF at day 4 and SOD-2 and COX-2 at day 7. The results suggest that the CE promoted the regulation of proteins and helped to accelerate the processes involved in healing, promoting early angiogenesis. This led to an increase in the re-epithelialized surface, with significant mitotic activity. Maturation of collagen fibers was also enhanced, which may affect the resistance of the extracellular matrix. PAS indicated a correlation between the rate of diffusion and biological events during the healing process. The CE from P. pluviosa appears promising as an aid in healing.
Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Extratos Vegetais/química , Reepitelização/efeitos dos fármacos , Pele/efeitos dos fármacos , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/normas , Ratos , Ratos Wistar , Pele/irrigação sanguínea , Pele/lesões , Pele/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ferimentos não Penetrantes/genética , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
Approximately 70% of the Brazilian production of guaraná (Paullinia cupana) seeds is absorbed by the beverage industries. Guaraná has several pharmacological properties: energy stimulant, antimicrobial, chemoprophylactic, antigenotoxic, antidepressive, anxiolytic, and anti-amnesic effects. Supercritical carbon dioxide extraction of bioactive compounds from guaraná seeds was carried out and optimized by an orthogonal array design (OA9(3(4))). The factors/levels studied were: modifier(s) (ethanol and/or methanol), extraction time (20, 40, and 60min), temperature (40, 50, and 60°C), and pressure (100, 200, and 300bar). The statistical design was repeated with increasing proportions of modifiers. The percentage of modifier used was proportional to the amount of polar compounds extracted. The best conditions for the supercritical extraction, based on the content of polyphenols, epicatechin/catechin quantification, yield and operating cost, proved to be: 40% ethanol:methanol during 40min, under 40°C, and 100bar. The temperature had a significant effect on the total phenolic content.
Assuntos
Cafeína/química , Paullinia/química , Extratos Vegetais/química , Polifenóis/química , Sementes/química , Anti-Infecciosos/química , Brasil , Catequina/química , Cromatografia Líquida de Alta Pressão , Etanol/química , Metanol/química , Microscopia Eletrônica de Varredura , Pressão , Controle de Qualidade , Staphylococcus aureus/efeitos dos fármacos , TemperaturaRESUMO
The aim of this study was evaluate the in vitro antifungal activity of crude extracts from Eugenia uniflora, Libidibia ferrea and Psidium guajava. The extracts were obtained by turbo-extraction using water (AQ) or acetone-water (AC-W) (7:3, v/v) as solvents and lyophilized to obtain the crude extracts (CE). The CE were characterized by UV-Vis, TLC and HPLC. The activity of CEs was investigated against clinical isolates of Candida spp. and the Minimum Inhibitory Concentration (MIC), MIC50 and MIC90 were determinated. The analysis by TLC showed that all CEs presented polyphenols (flavonoids and tannins). The CEs from E. uniflora showed higher amount of polyphenols (30.35 ± 2.15%, AC-W) and the HPLC analysis revealed the tannins in all extracts. The CEs of E. uniflora showed MIC range from 1.9 to 500.0 µg/mL, and lower values of MIC50 and MIC90 against non-albicans Candida isolates. Regarding L. ferrea and P. guajava, the results showing MIC from 3.9 to 1000.0 µg/mL (CE-AQ) against C. albicans. The results demonstrate antifungal performance from CE against various species of Candida spp., suggesting that the herbal species may be use as new potential antifungal agents. Additionally, the polyphenol content can play a pivotal role in the antifungal properties of CE.
Assuntos
Técnicas In Vitro/métodos , Extratos Vegetais/efeitos adversos , Polifenóis/análise , Compostos Fitoquímicos , Antifúngicos/administração & dosagem , Flavonoides/farmacocinética , Testes de Sensibilidade Microbiana/métodos , Cromatografia Líquida de Alta Pressão/métodosRESUMO
This study was carried out to determine the acute toxicity of total barbatimão extract (LD(50)) after oral administration to mice, and its effect on certain biochemical parameters in plasma of rats after 30 days of administration. The LD(50) value of the extract was 2699 mg/kg. A daily oral administration of extracts at 800 and 1600 mg/kg doses for 30 days caused a decrease in body weight, thymic involution, and an increase of plasma glucose and aspartate aminotransferase levels in the animals. The results showed that the extract administered in a prolonged period produced toxic effects in the experimental animals.
Assuntos
Fabaceae , Extratos Vegetais/toxicidade , Plantas Tóxicas/toxicidade , Administração Oral , Animais , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Testes de Função Renal , Dose Letal Mediana , Leucócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Ratos , Ratos WistarRESUMO
Abstract Seeds of guarana (Paullinia cupana Kunth, Sapindaceae) feature diverse pharmacological functions, for example, antimicrobial, antioxidant, anticarcinogenic, stimulating, and cognitive functions, as well as liver protection and weight loss. Many of these actions are probably due to the high content of methylxanthines and tannins in its seeds. In Brazil, the world's largest producer of guarana, the plant material is predominantly used in the soft drinks industry, although it is also used in the cosmetic and pharmaceutical industries. Although the Amazon region has the largest cropping area, the state of Bahia is the main guarana producer in Brazil (71%). This review focuses mainly on the possible pharmacological actions of guarana that have been investigated. Moreover, it discusses less-considered topics, such as the toxicology and quality control of seeds and extractives of guarana that will ultimately influence the safety of its use. In addition, it presents a detailed discussion of the methods used to prepare herbal drugs and their extracts, focusing on the importance of standardization and on the direct impact of preparatory factors, on the pharmacological properties of guarana extracts.
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Abstract Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the treatment of stress, sexual impotence and memory deficits. To our knowledge, there is no analytical method described in literature for simultaneous quantification of catuaba extract marker substances in biological matrices. The aim of this study was to develop and validate a bioanalytical method by LC-MS/MS to quantify epicatechin and procyanidin B2 in rat plasma after administration of standardized extract of T. catigua. Chromatographic separation was achieved with a C18 column, methanol and 0.1% aqueous formic acid at a flow rate of 0.25 ml/min. Detection was performed using electrospray ionization in negative mode. The lower limits of quantification were 5 ng/ml and 12.5 ng/ml for procyanidin B2 and epicatechin, respectively. Intra- and inter-day assays variability were less than 15%. The extraction recovery was 104% for epicatechin and 74% for procyanidin B2 using one-step liquid-liquid extraction with ethyl acetate. Epicatechin and PB2 were detected in plasma up to 300 min after oral administration of 400 mg/kg of standardized extract of T. catigua in rats. This rapid and sensitive method for the analysis of the epicatechin and procyanidin B2 in rat plasma can be applied to pharmacokinetic studies.
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The genus Tagetes constitutes a group of antagonistic plant species that are cytotoxic against plant pathogenic nematodes, with T. patula being particularly efficient. The aim of this study was to evaluate the in vitro effect of extracts and semi-purified fractions of T. patula flowers on eggs and second-stage juveniles (J2) of Meloidogyne incognita, M. javanica, and M. paranaensis, as well as to verify the nematicidal effect of the flavonoids present in T. patula flowers. Extracts and semi-purified fractions were obtained from dried T. patula flowers after maceration and liquidification, yielding crude aqueous (CAE) and crude ethanol-water (CEWE) extracts. Dried flowers were also treated with n-hexane to obtain a crude defatted aqueous extract (CDAE) and a crude ethanol-water defatted extract (CEWDE). Then, the CEWE was fractionated, and the ethyl acetate (EAF), ethanol (EF), methanol (MF), and ethanol:water (EWF) fractions were obtained. CAE, CEWE, CDAE, and CEWDE were tested to evaluate their effects on hatching, mobility, and mortality of J2 of M. incognita, M. javanica, and M. paranaensis. EAF, EF, MF, and EWF fractions were tested on the same variables of M. incognita. All extracts significantly reduced J2 hatching of M. incognita, M. javanica, and M. paranaensis when compared to water and water + DMSO. CEWE had nematicidal effects on the three evaluated species, whereas CEWDE demonstrated nematicidal effects against M. incognita and M. javanica, and nematostatic effects on M. paranaensis. This toxic effect showed by CEWE may be related to the high content of quercetin, a major substance present in this sample. It was also observed that EAF accentuated the nematicidal response on Meloidogyne spp., suggesting that other medium polarity (methoxylated) flavonoids act as nematotoxic substances. Thus, these results suggest that quercetin contributes significantly to the nematicidal activity of CEWE and EAF.(AU)
Entre as espécies de plantas antagonistas, as do gênero Tagetes apresentam citotoxicidade contra fitonematoides, sendo que T. patula mostra-se eficiente. Assim, objetivou-se avaliar o efeito in vitro de extratos e frações semipurificadas de flores de T. patula sobre ovos e juvenis de segundo estádio (J2) de Meloidogyne incognita, M. javanica e M. paranaensis, e a capacidade nematicida dos flavonoides presentes nas flores de T. patula. Os extratos e frações semipurificadas foram preparados a partir de flores secas de T. patula, que após maceração foram submetidas à turbólise, obtendo-se os extratos bruto aquoso (EBA) e bruto etanol-água (EBEA). Também houve tratamento de flores secas com n-hexano para a obtenção do extrato bruto aquoso desengordurado (EBAD) e do extrato bruto etanol-água desengordurado (EBEAD). Em seguida, o EBEA foi fracionado, sendo obtidas as frações acetato de etila (FAE), etanólica (FE), metanólica (FM) e etanol:água (FEA). O efeito dos extratos EBA, EBEA, EBAD e EBEAD foram avaliados sobre a eclosão, mobilidade e mortalidade de J2 de M. incognita, M. javanica e M. paranaensis. As frações FAE, FE, FM e FEA foram avaliadas frente a M. incognita usando as mesmas variáveis. Os extratos reduziram significativamente a taxa de eclosão de J2 de M. incognita, M. javanica e M. paranaensis, quando comparados com água e água + DMSO. Quanto ao efeito dos extratos, observou-se que EBEA apresentou efeito nematicida para as três espécies avaliadas, e EBEAD demonstrou capacidade nematicida contra M. incognita e M. javanica, e sendo nematostático para M. paranaensis. Tal capacidade pode estar relacionada com o alto teor de quercetina (substância majoritária no EBEA). Observou-se, também, que o fracionamento químico e a obtenção da FAE acentuaram a resposta nematicida sobre Meloidogyne spp., sugerindo que outros flavonoides de média polaridade (metoxilados) atuam como substâncias nematotóxicas.(AU)
Assuntos
Tagetes/química , Nematoides/química , Nematoides/enzimologia , Flavonoides/análise , Flavonoides/química , TylenchoideaRESUMO
The genus Tagetes constitutes a group of antagonistic plant species that are cytotoxic against plant pathogenic nematodes, with T. patula being particularly efficient. The aim of this study was to evaluate the in vitro effect of extracts and semi-purified fractions of T. patula flowers on eggs and second-stage juveniles (J2) of Meloidogyne incognita, M. javanica, and M. paranaensis, as well as to verify the nematicidal effect of the flavonoids present in T. patula flowers. Extracts and semi-purified fractions were obtained from dried T. patula flowers after maceration and liquidification, yielding crude aqueous (CAE) and crude ethanol-water (CEWE) extracts. Dried flowers were also treated with n-hexane to obtain a crude defatted aqueous extract (CDAE) and a crude ethanol-water defatted extract (CEWDE). Then, the CEWE was fractionated, and the ethyl acetate (EAF), ethanol (EF), methanol (MF), and ethanol:water (EWF) fractions were obtained. CAE, CEWE, CDAE, and CEWDE were tested to evaluate their effects on hatching, mobility, and mortality of J2 of M. incognita, M. javanica, and M. paranaensis. EAF, EF, MF, and EWF fractions were tested on the same variables of M. incognita. All extracts significantly reduced J2 hatching of M. incognita, M. javanica, and M. paranaensis when compared to water and water + DMSO. CEWE had nematicidal effects on the three evaluated species, whereas CEWDE demonstrated nematicidal effects against M. incognita and M. javanica, and nematostatic effects on M. paranaensis. This toxic effect showed by CEWE may be related to the high content of quercetin, a major substance present in this sample. It was also observed that EAF accentuated the nematicidal response on Meloidogyne spp., suggesting that other medium polarity (methoxylated) flavonoids act as nematotoxic substances. Thus, these results suggest that quercetin contributes significantly to the nematicidal activity of CEWE and EAF.
Entre as espécies de plantas antagonistas, as do gênero Tagetes apresentam citotoxicidade contra fitonematoides, sendo que T. patula mostra-se eficiente. Assim, objetivou-se avaliar o efeito in vitro de extratos e frações semipurificadas de flores de T. patula sobre ovos e juvenis de segundo estádio (J2) de Meloidogyne incognita, M. javanica e M. paranaensis, e a capacidade nematicida dos flavonoides presentes nas flores de T. patula. Os extratos e frações semipurificadas foram preparados a partir de flores secas de T. patula, que após maceração foram submetidas à turbólise, obtendo-se os extratos bruto aquoso (EBA) e bruto etanol-água (EBEA). Também houve tratamento de flores secas com n-hexano para a obtenção do extrato bruto aquoso desengordurado (EBAD) e do extrato bruto etanol-água desengordurado (EBEAD). Em seguida, o EBEA foi fracionado, sendo obtidas as frações acetato de etila (FAE), etanólica (FE), metanólica (FM) e etanol:água (FEA). O efeito dos extratos EBA, EBEA, EBAD e EBEAD foram avaliados sobre a eclosão, mobilidade e mortalidade de J2 de M. incognita, M. javanica e M. paranaensis. As frações FAE, FE, FM e FEA foram avaliadas frente a M. incognita usando as mesmas variáveis. Os extratos reduziram significativamente a taxa de eclosão de J2 de M. incognita, M. javanica e M. paranaensis, quando comparados com água e água + DMSO. Quanto ao efeito dos extratos, observou-se que EBEA apresentou efeito nematicida para as três espécies avaliadas, e EBEAD demonstrou capacidade nematicida contra M. incognita e M. javanica, e sendo nematostático para M. paranaensis. Tal capacidade pode estar relacionada com o alto teor de quercetina (substância majoritária no EBEA). Observou-se, também, que o fracionamento químico e a obtenção da FAE acentuaram a resposta nematicida sobre Meloidogyne spp., sugerindo que outros flavonoides de média polaridade (metoxilados) atuam como substâncias nematotóxicas.
Assuntos
Flavonoides/análise , Flavonoides/química , Nematoides/enzimologia , Nematoides/química , Tagetes/química , TylenchoideaRESUMO
This study evaluated the technological feasibility of producing a semipurified extract of guaraná (Paullinia cupana Kunth, Sapindaceae) in tablet form, using a direct-compression process. Maltodextrin and gum arabic were used to produce the extract microparticles, in order to protect the microparticles against such factors as temperature, oxidation, and humidity. Using pharmacopoeial methodologies, technological and physicochemistry tests (determination of residual moisture, of bulk and tapped density, Hausner ratio, compressibility and compactibility index, appearance, mean weight, hardness, friability, disintegration time, determination of EPA amount in tablets and in vitro release profile) were conducted. The formulation containing 200 mg of microparticles, 170 mg microcrystalline cellulose, and 10 mg lactose gave the best results in terms of hardness (116 N), friabilility (0.28%), mean weight (0.3821 g), and disintegration time (25 min) for a tablet designed for oral administration. The results met pharmacopoeial specifications, and the tablets are suitable for oral administration.