GC/MS and 2D NMR-based approach to evaluate the chemical profile of hydroalcoholic extract from Agaricus blazei Murill and its anti-inflammatory effect on human neutrophils.

ETHNOPHARMACOLOGICAL RELEVANCE: Agaricus blazei Murill (AbM) is one of the main mushrooms used for medicinal purposes. The use of AbM in the preparation of teas is widespread mainly in Asian countries, while in Brazil it is used as a functional food to combat inflammatory diseases and cancer. AIM OF THE STUDY: The main focus of this study was the characterization of the chemical profile of the hydroalcoholic extract of Agaricus blazei Murill (AbE), as well as the evaluation of its cytotoxic and anti-inflammatory potential using human neutrophils. MATERIALS AND METHODS: The extract was prepared by dynamic maceration using a mixture of ethanol and water (70/30, v v-1) as solvent. The chemical profile characterization was carried out by 2D NMR and GC-MS techniques. The cytotoxicity of AbE was evaluated through studies of hemolytic potential, cell viability and membrane integrity. The anti-inflammatory activity was analyzed by a PMA-induced neutrophil degranulation assay. RESULTS: Chemical analysis of AbE revealed the presence of 28 metabolites in its composition, with mannitol as the major compound. AbE at 1-200 µg mL-1 and mannitol at 4-160 µg mL-1, showed low hemolytic and cytotoxic potential against human red blood cells and neutrophils. Furthermore, both were able to significantly reduce the release of myeloperoxidase. CONCLUSIONS: These results indicate that AbE is a promising natural product to be incorporated into pharmaceutical dosage forms intended for the adjuvant treatment of inflammatory diseases.

Avaliação in silico da atividade ansiolítica de compostos do extrato de camomila (Matricaria recutita) nos receptores GABAa humanos / In silico evaluation of the anxiolytic activity of compounds from chamomile (Matricaria recutita) extract in human GABAa receptors

Objetivo: Avaliar a possível atividade ansiolítica de compostos presentes no extrato padronizado de camomila por meio da interação com o receptor GABAa, como também analisar parâmetros farmacocinéticos das moléculas escolhidas por meio de ferramentas computacionais. Método: Simulação da interação proteína-ligante da apigenina, alfa-bisabolol e camazuleno, por meio de docagem molecular com o receptor GABAa, comparadas com diazepam. Por fim, os parâmetros farmacocinéticos dos três compostos foram calculados, usando a ferramenta on line SwissADME. Resultados: Alfa-bisabolol e camazuleno adequaram-se aos parâmetros farmacocinéticos favoráveis, enquanto a apigenina e o diazepam não atenderam ao perfil de ideal de biodisponibilidade. No estudo docking, as energias de ligação obtidas foram de -5-1 (a-bisabolol), -7,0 (camazuleno), -7,5 (diazepam), e -8.3 kcal/mol (apigenina); também foram observadas ligações do tipo hidrofóbicas, de Van der Waals e interações eletrostáticas. Conclusão: Os parâmetros analisados sugerem a atividade ansiolítica das moléculas estudas. Ademais, mais pesquisas in vivo devem ser realizadas a fim de elucidar os resultados e seus mecanismos e possíveis limitações em humanos.

Objective: To evaluate the possible anxiolytic activity of compounds present in standardized chamomile extract through interaction with the GABAa receptor and to analyze pharmacokinetic parameters of the chosen molecules through computational tools. Methods: Simulation of the protein-ligand interaction of apigenin, alpha-bisabolol, and camazulene by molecular docking with the GABAa receptor compared with diazepam. Finally, the pharmacokinetic parameters of the compounds were calculated using the SwissADME online tool. Results: Alpha-bisabolol and camazulene fit the favorable pharmacokinetic parameters, while apigenin and diazepam did not meet the ideal bioavailability profile. In the docking study. The binding energies obtained were -5-1 ( a-bisabolol), -7.0 (camazulene), -7.5 (diazepam), and -8.3 kcal/mol (apigenin). Hydrophobic bonds, Van der Waals and electrostatic interactions were observed. Conclusion: The parameters analyzed suggest an anxiolytic activity of the molecules studied. Also, more in vivo research to elucidate the results and their human and possible resources used in humans

Seroprevalence and risk factors of Chagas disease in a rural population of the Quixeré municipality, Ceará, Brazil

Abstract INTRODUCTION: This study estimated the seroprevalence and risk factors of Chagas disease (CD) in a population of the Quixeré municipality, Ceará. METHODS: We conducted serological methods to detect the Trypanosoma cruzi infection. The other variables were evaluated by a standardized questionnaire. RESULTS: The estimated prevalence of CD was 3.7%. Male sex, age >40 years, being farmers, low education level, origin from rural areas, and being born in Quixeré were significantly associated with infection. CONCLUSION: CD persists in this rural population of Northeast Brazil. Poverty, low education, and limited information regarding CD are critical issues that need to be addressed.

Justicia pectoralis, a coumarin medicinal plant have potential for the development of antiasthmatic drugs?

ABSTRACT Justicia pectoralis Jacq., Acanthaceae, is a medicinal plant found Central America. In the Northeast of Brazil, it is popularly known as "chambá" being extensively used in homemade preparations for the treatment of cough, bronchitis and asthma. The species is part of a public phytotherapy program in Brazil entitled "Farmácias Vivas", National Record of Plants of Interest to the National Health System and the National Formulary of Herbal medicines. This paper aims to critically review the available scientific literature regarding the health promoting effects of J. pectoralis var. stenophylla. The traditional uses, phytochemistry, pharmacological activities, toxicology, quality control and potential interactions with conventional drugs were included in the present review. Botanical, chemical and pharmacognostical studies stablished several parameters useful for quality control of plant drug, extracts and phytomedicine from aerial parts of J. pectoralis using as markers two bioactive coumarins. A wide range of evidence have demonstrated the anti-inflammatory, anti-nociceptive, anti-spasmodic, smooth muscle relaxant and anxiolytic effects of J. pectoralis and its chemical constituents. Pilot clinical studies showed the efficacy of a syrup preparation of J. pectoralis in the treatment of mild and moderate asthma. The pharmacological potential make these medicinal plants good candidates for the development of new phytomedicine for the treatment of asthma. However, a strong collaboration to bridge the gap between preclinical and clinical study is still necessary for the development of an effective medicine from J. pectoralis.

Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.

A hidroxiuréia (HU) constitui o avanço mais importante no tratamento da anemia falciforme (AF) por prevenir complicações e aumentar a qualidade de vida dos pacientes. Entretanto, alguns aspectos do tratamento com HU permanecem obscuros, incluindo a sua ação e potencial toxicidade em outras células sanguíneas, tais como neutrófilos. Este estudo utilizou a mensuração da lactato desidrogenase (LDH) e do metil tiazoltetrazólio (MTT) e o ensaio do cometa para investigar a citotoxicidade e índice de dano (ID) ao DNA em neutrófilos de pacientes com AF em uso do medicamento. Nos ensaios de LDH e MTT, observou-se além de ausência de toxicidade, uma ação citoprotetora no grupo de pacientes tratados, Grupo SSHU (n=21, 11 mulheres e 10 homens, com idades entre 19-63 anos), quando comparados aos pacientes sem tratamento, Grupo SS (n=20, 13 mulheres e 07 homens, 18-69 anos), e grupo de indivíduos saudáveis (AA) usado como controle (n=52, 28 mulheres e 24 homens, 19-60 anos), com redução significativa (p<0,001) na atividade de LDH e aumento no percentual de células viáveis pelo MTT (p<0,001). Entretanto, o grupo SSHU apresentou valores de ID significativamente elevados (49,57±6,0 U/A), quando comparados ao grupo AA (7,43 ± 0,94U/A) e grupo SS (22,73 ±5,58 U/A) (p<0,0001), especialmente quando tratados por períodos mais longos (>20 meses), demonstrando que apesar dos efeitos citoprotetores quanto à viabilidade celular, o uso da HU pode induzir lesão ao DNA de neutrófilos.

Contribuição para a validação do uso medicinal de Amburana cearensis (CUMARU) [manuscrito]: estudo farmacológico com o isocampferídeo e o amburosídio / Contribution to the validation of the medicinal use of Amburana cearensis (CUMARU) [manuscript]: pharmacological study with isocampferídeo and amburosídio

Amburana cearensis (Fabaceae) é uma árvore da caatinga nordestina, mais conhecida popularmente como cumaru. Suas cascas (caule) possuem um cheiro característico pela presença de cumarina, e são principalmente utilizadas no tratamento da bronquite, tosse e asma. O presente estudo procurou investigar os efeitos tóxicos e as atividades antiinflamatória, antioxidante e relaxante muscular do isocampferídio (ICPF, 3-metilflavonol) e/ou do amburosídio A (AMB, glucosídio fenólico) isolados das cascas do caule de A. cearensis. A administração intraperitoneal (i.p.) do ICPF ou do AMB em dose única (50 - 200 mg/kg) mostrou baixa toxicidade em camundongos. Na cultura primária de hepatócitos apenas o ICPF (100 μg/ml) reduziu significativamente a viabilidade celular, determinada pelo teste do MTT. O ICPF e o AMB (12,5 - 50 mg/kg, i.p.) apresentaram atividade antiinflamatória, observada inicialmente pela inibição do edema de pata induzido por carragenina-Cg, prostaglandina E2, dextrano-Dx, histamina ou serotonina e pela redução em 39 e 50% respectivamente do infiltrado de neutrófilos verificada pela análise histopatológica/morfométrica do edema induzido por Cg. O aumento da permeabilidade vascular induzido pelo Dx em camundongos, foi também significativamente inibido pelo ICPF ou AMB...