RESUMEN
microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.
Os microRNAs (miRNAs) são reconhecidos como biomarcadores do diabetes mellitus tipo 2 (DM2), úteis para a compreensão do metabolismo da doença, e possuem grande potencial como alvos terapêuticos. O aumento da expressão de BDNF e IGF1 está altamente envolvido nos benefícios as vias de insulina e glicose, porém, são regulados negativamente em condições de resistência à insulina, enquanto seu aumento de expressão está correlacionado com a melhora do metabolismo da glicose e da insulina. Estudos sugerem a regulação desses genes por microRNA em vários contextos diferentes, proporcionando uma nova abordagem de investigação para compreender o metabolismo do DM2 e revelar potenciais alvos terapêuticos. No presente estudo, investigamos em diferentes modelos animais (humanos, ratos e camundongos) miRNAs que têm como alvo BDNF e IGF1 em tecido muscular esquelético com condições fisiológicas de DM2. As análises foram realizadas utilizando ferramentas de bioinformática e bancos de dados para predição de miRNA, homologia molecular, validação experimental de interações, expressão na condição fisiológica estudada e interação em rede. Os resultados mostraram três candidatos a miRNAs para IGF1 (miR-29a, miR-29b e miR-29c) e um para BDNF (miR-206). As avaliações experimentais e a busca pela expressão no músculo esquelético de indivíduos com DM2 confirmaram a interação prevista entre miRNA-mRNA para miR-29b e miR-206 através de modelos humanos, ratos e camundongos. Essa interação foi reafirmada em múltiplas análises de rede. Em conclusão, nossos resultados mostram a relação de regulação entre miR-29b e miR-206 com os genes investigados, em diversos tecidos, sugerindo um padrão de inibição. Contudo, esses dados mostram um grande número de possíveis processos fisiológicos de interação para perspectivas biotecnológicas.
Asunto(s)
Humanos , Ratones , Ratas , Resistencia a la Insulina , Biomarcadores , Terapia Genética , Diabetes Mellitus Tipo 2/metabolismoRESUMEN
microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Insulinas , MicroARNs , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Biología Computacional , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/uso terapéutico , Humanos , Resistencia a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Insulinas/uso terapéutico , Ratones , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/uso terapéutico , RatasRESUMEN
BACKGROUND: Diabetes mellitus is a syndrome with multiple etiologies involving insulin, in which there is a lack of production and/or loss of sensitivity to this hormone resulting in insulin resistance. Treatment and control of this disease requires changes in diet, use of medication, and lifestyle, such as physical activity. These modifications may compromise quality-of-life if there is no proper guidance for the treatment or alert to possible complications caused by the disease. METHODS: This study aimed to evaluate biochemical and hematological parameters, and to assess brain derived neurotrophic factor levels in diabetic Wistar rats submitted to chronic physical exercise. RESULTS: The results demonstrated an increase in plasma concentration of brain-derived neurotrophic factor (BDNF) in association with hyperglycemia reduction in diabetic animals. DISCUSSION: The results obtained suggest that there is a regulation of glucose homeostasis between peripheral tissues and the central nervous system. Exercise-induced BDNF also improved levels of glycemia, body weight, and dyslipidemia. In hematological evaluation, BDNF increase was positively correlated with an improvement in leukocyte parameters. Electrophoresis analyses demonstrated a reduction in levels of pro-inflammatory proteins, lipoprotein fractions, and albumin preservation in diabetic animals trained with elevated concentration of plasma BDNF. CONCLUSION: In conclusion, this study demonstrated that chronic exercise was able to elevate BDNF levels in plasma, which resulted directly in positive hypoglycemic activity in diabetic animals and a reduction of the metabolic syndrome associated with diabetes mellitus.
RESUMEN
AIM: The goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump. METHODS AND RESULTS: Microdilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 µg ml-1 ; Log P 2·95) < Riparin-C (MIC 102 µg ml-1 ; Log P 3·22) < Riparin-E (MIC 16 µg ml-1 ; Log P 3·57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect. CONCLUSIONS: Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph. aureus.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Benzamidas/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Benzamidas/química , Farmacorresistencia Bacteriana , Fluoroquinolonas/farmacologíaRESUMEN
The use of natural products has a long tradition in medicine, and they have proven to be an important source of lead compounds in the development of new drugs. Among the natural compounds, terpenoids present broad-spectrum activity against infective agents such as viruses, bacteria, fungi, protozoan and helminth parasites. In this study, we report a biological screening of 38 chemically characterized terpenes from different classes, which have a hydroxyl group connected by hydrophobic chain or an acceptor site, against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. In vitro bioassays revealed that 3,7-dimethyl-1-octanol (dihydrocitronellol) (10) was the most active terpene (IC50 values of 1352 µM) and, thus, we investigated its antischistosomal activity in greater detail. Confocal laser scanning microscopy revealed that compound 10 induced severe tegumental damage in adult schistosomes and a correlation between viability and tegumental changes was observed. Furthermore, we compared all the inactive compounds with dihydrocitronellol structurally by using shape and charge modeling. Lipophilicity (miLogP) and other molecular properties (e.g. molecular polar surface area, molecular electrostatic potential) were also calculated. From the 38 terpenes studied, compound 10 is the one with the greatest flexibility, with a sufficient apolar region by which it may interact in a hydrophobic active site. In conclusion, the integration of biological and chemical analysis indicates the potential of the terpene dihydrocitronellol as an antiparasitic agent.
Asunto(s)
Parásitos , Parasitología , Bacterias , Preparaciones Farmacéuticas , HongosRESUMEN
Morphometric analysis of Schistosoma mansoni male worms obtained from AKR/J and Swiss mice was carried out. Rodents infected by the intraperitoneal route with 80 cercariae of the schistosome (LE strain) were killed by cervical dislocation at 45 and 60 days post-infection and both peritoneal lavage and perfusion of the portal system were performed for the recovery of adult worms. Characteristics including total body length, the distance between oral and ventral suckers, extension of testicular mass and the number of testes were considered in the morphological analysis. Changes that occurred in S. mansoni recovered from the peritoneal cavity or from the portal system of AKR/J and Swiss mice included total body length and reproductive characteristics. Significant morphometric alterations were also observed when worms recovered from the portal system of both strains of mice were compared with the schistosomes obtained from hamsters (Mesocricetus auratus), the vertebrate host in which the LE strain had been adapted and maintained by successive passages for more than four decades. The present results reinforce the idea that S. mansoni has high plastic potential and adaptive capacity.
Asunto(s)
Cavidad Peritoneal/parasitología , Sistema Porta/parasitología , Schistosoma mansoni/anatomía & histología , Schistosoma mansoni/fisiología , Esquistosomiasis mansoni/parasitología , Animales , Biometría , Cricetinae , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos AKRRESUMEN
In the West, the consumption of medicinal plants is increasing strongly, and up to 40% of the population use medicinal plants and phytotherapic preparations regularly, in the belief that they are innocuous and/or safe. However, in most cases there is no scientific proof of their pharmacological and toxicological properties. The aim of this study was to carry out a bibliographical review of the toxicological properties of Casearia sylvestris Swartz and collect data providing a basis for its rational use. Some studies validate classical therapeutic indications of C. sylvestris, such as to treat diarrhea and snakebites, justifying its empirical use. Nevertheless, there are few reports about its toxicological properties and these present only limited findings, describing results as 50% lethal dose (LD50) and the acute toxicity of its constituents. Currently, research is insufficient to ensure safety of popular preparations based on C. sylvestris. Therefore, it is necessary to make a fuller assessment of its deleterious profile, especially with respect to the toxic potential of its constituents, as well as its capacity to harm target organs and organic systems...
No Ocidente, o consumo de plantas medicinais vem aumentando substancialmente, onde cerca de 40% da população utiliza regularmente plantas medicinais e preparações fitoterápicas sob o rótulo de serem produtos inócuos ou seguros. Porém, na maioria das vezes, não há comprovação científica de suas propriedades farmacológicas e toxicológicas. O objetivo deste trabalho foi realizar um levantamento bibliográfico sobre as propriedades toxicológicas da Casearia sylvestris Swartz e coletar dados que fundamentem seu uso racional. Alguns estudos validam indicações terapêuticas clássicas da C. sylvestris como antidiarréico e no tratamento de ferimentos ofídicos, fundamentando seu uso empírico. Porém, poucos trabalhos relatam suas propriedades toxicológicas, havendo apenas abordagens limitadas em torno da Dose Letal 50% e da toxicidade aguda de seus constituintes. Até o presente momento, as pesquisas são insuficientes para garantir a segurança de preparações populares à base de C. sylvestris. Portanto, há necessidade de avaliar melhor seu perfil deletério, principalmente, no que diz respeito ao potencial tóxico de seus constituintes, assim como a sua capacidade lesiva sobre órgãos-alvos e sistemas orgânicos...
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Humanos , Casearia/efectos adversos , Casearia/toxicidad , Diterpenos de Tipo Clerodano , Plantas MedicinalesRESUMEN
O presente estudo teve como objetivo investigar o efeito anticonvulsivante do p-cimeno (CIM), bem como verificar a concentração das monoaminas (dopamina(DA), noradrenalina (NA), serotonina (5-HT), e seus metabólitos (ácido dihidroxifenilacético (DOPAC), ácidohomovanílico (HVA) e ácido 5-hidroxi-indol-acético (5-HIAA)) no hipocampo de camundongos tratados com cloridrato de pilocarpina 400 mg/kg (P400; i.p.) e nos grupos tratados com a associação de CIM (50, 100 ou150 mg/kg) e P400. Nesse estudo foi avaliada a latência para a primeira crise epiléptica e a taxa de mortalidade. Os resultados revelaram que o CIM produziu um aumento na latência para primeira crise epilética, bem como promoveu uma proteção significativa contra a mortalidade induzida pelo processo convulsivo. O monoterpeno nas doses testadas também foi capaz de produzir um aumento da latência para instalação do estado de mal epilético induzido por pilocarpina. Além disso, durante os estudos para identificar o mecanismo de ação nenhum dos efeitos do p-cimeno nesse modelo foram bloqueados pelo pré-tratamento com atropina. Complementando os estudos para identificar o provável mecanismo de ação do p-cimeno, foi verificado que os efeitos desse monorterpeno foram revertidos pelo flumazenil, um antagonista do sistema GABAérgico, sugerindo que esse monoterpeno pode atuar por meio desse sistema. Também, em nossos resultados também foi visto uma diminuição dos níveis de DA e um aumento do conteúdo de seus metabólitos (DOPAC e HVA) durante as crises epilépticas. Por outro lado foi detectado um aumento na concentração de NA e 5-HT, e uma diminuição no metabólito da 5-HT (5-HIAA) durante as crises epilépticas. Dessa forma, o CIM na presença do estímulo convulsivo, reverte os efeitos produzidos nos níveis das monoaminas e seus metabólitos observados durante as crises epilépticas, sugerindo que este monoterpeno produz efeito anticonvulsivante por meio da modulação direta do sistema GABAérgico e indiretamente por...
The aim of this study was to investigate the anticonvulsant effect of p-cymene (CYM) and to determine the concentrations of monoamines (dopamine (DA), noradrenaline (NA) and serotonin (5-HT)), and their metabolites (dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) in the hippocampus of mice treated with pilocarpine hydrochloride 400 mg/kg (P400; i.p.) and in groups treated with a combination of CYM (50,100 or 150 mg/kg) and P400. We assessed the latency to the first epileptic seizure and the mortality rate. Results showed that CYM produced an increase in latency to the first seizure, as well as providing significant protection against mortality induced by seizures. Higher doses of the monoterpene were also able to prolong the latency to the onset of status epilepticus induced by pilocarpine. Moreover, in an experiment to throw light on the mechanism of action of p-cymene, none of its effects was blocked by pretreatment with atropine. In further studies to identify the probable mechanism of CYM, it was observed that the effectsof this monoterpene were reversed by flumazenil, anantagonist of the GABAergic system, suggesting that it may act through this cerebral system. Furthermore, our results also showed a fall in DA levels and an increase in the contents of its metabolites (DOPAC and HVA) during seizures. On the other hand, increases in NA and 5-HT concentrations and a decrease in that of the 5-HTmetabolite (5-HIAA) were detected during seizures. Thus, CYM, in the presence of a convulsant stimulus, reverses the effects on levels of monoamines and their metabolites observed during seizure activity, suggesting that this monoterpene produces its anticonvulsant effect by modulating the GABAergic system directly and/or indirectly, through changes in monoamine (DA, NA and 5-HT) contents opposite to those observed during the convulsive process in the hippocampal region. However,further studies are necessary to...
Asunto(s)
Animales , Ratones , Anticonvulsivantes , Monoterpenos , RatonesRESUMEN
A Mikania glomerata é uma planta pertencente à família Asteraceae que é bastante utilizada na medicina popular devido às suas ações broncodilatadora, antiasmática, expectorante e antitussígena. O objetivo do presente estudo foi determinar as propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata, bem como, avaliar a toxicidade em camundongos após tratamento agudo com doses repetidas do extrato etanólico padronizado preparado a partir das folhas dessa espécie. Durante o estudo das propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata foram feitas as determinações da densidade bruta e de compactação, do teor de cinzas totais, do teor de umidade, e da granulometria. De acordo com os resultados obtidos podemos sugerir que o pó pode ser usado na formulação de uma forma farmacêutica sólida. Na segunda parte do estudo foi determinada a Dose Letal 50% (DL50), bem como, realizada a análise morfológica macroscópica e avaliados a toxicidade aguda com doses repetidas e os parâmetros bioquímicos e hematológicos de camundongos. De acordo com os dados obtidos na segunda parte deste estudo podemos sugerir que o extrato etanólico pode ser usado de forma segura em humanos, uma vez que apresentou valor de DL50 de aproximadamente 3000 mg Kg-1), bem como, não produziu nenhuma alteração morfológica nos principais órgãos, e nem provocou alterações nos parâmetros bioquímicos e hematológicos de camundongos.
The Mikania glomerata is a plant belonging to the Asteraceae that is widely used in folk medicine because of its bronchodilator, antiasthmatic, expectorant and antitussive actions. The aim of this study was to determine the physicochemical properties of the powder obtained from the leaves of M. glomerata, and to evaluate its toxicity in mice after acute treatment with repeated doses of standardized ethanol extract prepared from the leaves of this plant species. We determined the bulk and packing density, the total ash content, the moisture content and the particle size. The results suggest that the powder can be used in the formulating of a solid pharmaceutical form. In the second part of this study, we determined the 50% lethal dose (LD50), performed the gross morphological analysis and evaluated the acute toxicity from the use of repeated doses and the biochemical and hematologic parameters in mice. The data obtained in this part suggest that the ethanol extract can be used safely in humans, since it has a LD50 value of approximately 3000 mg kg -1 and produced no morphological changes in the major organs, or caused alterations in the biochemical and hematological parameters in mice.
Asunto(s)
Extractos Vegetales/análisis , Hojas de la Planta/clasificación , Asteraceae/clasificación , /análisis , Mikania/efectos adversos , Plantas Medicinales/metabolismoRESUMEN
2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, 5TIO1, is a new 2-aminothiophene derivative with promising pharmacological activities. The aim of this study was to evaluate its antioxidant activity in different areas of mice central nervous system. Male Swiss adult mice were intraperitoneally treated with Tween 80 dissolved in 0.9% saline (control group) and 5TIO1 (0.1, 1, and 10 mg kg(-1)). Brain homogenates-hippocampus, striatum, frontal cortex, and cerebellum-were obtained after 24 h of observation. Superoxide dismutase and catalase activities, lipid peroxidation and nitrite content were measured using spectrophotometrical methods. To clarify the 5TIO1's mechanism on oxidative stress, western blot analysis of superoxide dismutase and catalase was also performed. 5TIO1 decreased lipid peroxidation and nitrite content in all brain areas and increased the antioxidant enzymatic activities, specially, in cerebellum. The data of Western blot analysis did not demonstrate evidence of the upregulation of these enzymes after the administration of this compound. Our findings strongly support that 5TIO1 can protect the brain against neuronal damages regularly observed during neuropathologies.
Asunto(s)
Antioxidantes/farmacología , Encéfalo/metabolismo , Estrés Oxidativo , Bases de Schiff/farmacología , Tiofenos/farmacología , Animales , Antioxidantes/química , Encéfalo/efectos de los fármacos , Catalasa/metabolismo , Cerebelo/enzimología , Cerebelo/metabolismo , Cuerpo Estriado/enzimología , Cuerpo Estriado/metabolismo , Lóbulo Frontal/enzimología , Lóbulo Frontal/metabolismo , Hipocampo/enzimología , Hipocampo/metabolismo , Inyecciones Intraperitoneales , Peroxidación de Lípido , Masculino , Ratones , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Bases de Schiff/química , Superóxido Dismutasa/metabolismo , Tiofenos/químicaRESUMEN
A caracterização química do óleo essencial de folhas de Citrus limon (Rutaceae) resultou na identificação de mistura de monoterpenos (limoneno, linalol, cis-óxido de limoneno, trans-óxido de limoneno, citronelal, neral, geranial, nerol e acetato de geranil). As estruturas dos compostos do óleo essencial foram identificadas por GC/MS, por comparação com dados da literatura. Os efeitos da administração crônica oral do óleo essencial de folhas de Citrus limon foram investigados sobre parâmetros bioquímicos e hematológicos em camundongos Swiss machos. Os animais (n = 10/grupo) foram tratados por via oral diariamente durante 30 dias com óleo essencial de folhas de Citrus limon, nas doses de 50, 100 ou 150 mg kg-1 de massa corporal e os parâmetros bioquímicos e hematológicos avaliados. O tratamento não causou nenhuma morte ou toxicidade nos animais. A administração do óleo essencial não alterou os parâmetros bioquímicos e hematológicos e a massa dos órgãos, exceto por diminuição de 21 e 11% em uréia e ácido úrico, respectivamente, e 9%, nos níveis plasmáticos de aspartato transaminase (AST). Para os parâmetros hematológicos, houve pequenas mudanças nas contagens de neutrófilos, linfócitos, eosinófilos e monócitos, mas estes não foram diferentes dos valores de referência. Além disso, houve diminuição significativa nos triglicerídeos detectado nos animais tratados com dose de 150 mg kg-1 de óleo essencial. Em conclusão, a administração crônica de óleo essencial não induziu nenhum efeito de risco na maioria dos parâmetros bioquímicos e hematológicos estudados em camundongos Swiss machos. No entanto, a diminuição dos níveis de uréia e ácido úrico em doses elevadas, sugere um possível efeito de insuficiência renal e aumento no teor de AST, sugerindo possível sobrecarga hepática que deve ser investigada com mais detalhe.
The chemical characterization of the essential oil of Citrus limon (Rutaceae) leaves resulted in the identification of a mixture of monoterpenes (limonene, linalool, cis-limonene-oxide, trans-limonene-oxide, citronellal, neral, geranial, nerol e geranyl acetate). The structures of the compounds of essential oil were identified by GC/MS by comparison with literature data. The effects of the chronic oral administration of the essential oil of Citrus limon leaves were investigated on biochemical and hematological parameters in male adult Swiss mice. These animals (n=10/group) were orally treated daily for 30 days with essential oil of Citrus limon leaves with doses of 50, 100 or 150 mg kg-1 body weight and the biochemical and hematological parameters were evaluated. The treatment did not cause any deaths or toxicity in the animals. The administration of essential oil did not change biochemical and hematological parameters and organ weight, except for decreases of 21 and 11% in blood urea nitrogen and uric acid respectively, and 9%, in aspatate transaminase (AST) plasma level. For the hematological parameters, there were slight changes in which neutrophil, lymphocytes, eosinophils and monocyte counts were not different from the reference values. In addition, with respect to serum triglyceride a significant decrease was detected in mice treated with a dose of 150 mg kg-1 of essential oil from Citrus limon. In conclusion, the chronic administration of essential oil of Citrus limon leaves did not induce any harzadous effects on most of the biochemical and hematological parameters studied in male adult Swiss mice. However, the decrease in the levels in blood urea nitrogen and uric acid in high doses, suggests a possible effect of renal insufficiency and an increase in AST content, which in its turn, suggests a possible hepatic overload which should be investigated in more details.
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Animales , Masculino , Femenino , Ratones , Aceites Volátiles/análisis , Citrus/clasificación , Hojas de la Planta/metabolismo , Bioquímica , HematologíaRESUMEN
Mikania glomerata (Asteraceae) é bastante utilizada na medicina popular devido às suas ações broncodilatadora, antiasmática, expectorante e antitussígena. O objetivo do presente estudo foi determinar propriedades físicoquímicas do pó obtido a partir das folhas de M. glomerata, bem como avaliar a toxicidade em camundongos após tratamento agudo com doses repetidas do extrato etanólico padronizado a 70% preparado durante 30 dias consecutivos. No estudo das propriedades físicoquímicas fez-se a determinação da densidade bruta e de compactação, do teor de cinzas totais, do teor de umidade e da granulometria. De acordo com os resultados obtidos o pó pode ser usado na formulação de uma forma farmacêutica sólida, uma vez que suas propriedades físico-químicas são compatíveis com o desenvolvimento desse tipo de formulação. Na segunda parte do estudo foi determinada a dose letal 50% (DL50) em camundongos, e na análise morfológica macroscópica dos principais órgãos e avaliada a toxicidade aguda com doses repetidas em parâmetros bioquímicos e hematológicos de camundongos. Os resultados sugerem que o extrato etanólico padronizado a 70% pode ser usado de forma segura, uma vez que apresentou um valor para a DL50 (~3000 mg kg-1) que pode ser classificado na categoria nociva, e não produziu nenhuma alteração morfológica nos principais órgãos e em parâmetros bioquímicos e hematológicos de camundongos.
Mikania glomerata Sprengel is a plant from the Asteraceae family and it is widely used in folk medicine because of its bronchodilating, anti-asthmatic, expectorant and antitussive effects. The purpose of this study was to determine the physicochemical properties of the powder obtained from the leaves of M. glomerata, and to evaluate the toxicity in mice after an acute treatment with repeated doses of standardized 70% ethanol extract prepared from the leaves during 30 consecutive days. To study the physicochemical properties of the powder, we conducted a determination of the bulk density and compaction, the total ash content, the moisture content and particle size. According to the results obtained, we suggest that the powder can be used to formulate a solid dosage form, since its physicochemical properties matches the development of this type of formulation. In the second part of the study, it was determined a lethal dose in the order of 50% (LD50), along with a gross morphological analysis and the evaluation of the acute toxicity with repeated doses, in the terms of biochemical and hematological parameters of mice. According to the results from the second phase, we suggest that the 70% ethanol extract can be used safely in humans, since it presented a value for the LD50 (~ 3000 mg kg-1) that can be classified as 'harmful'. It also did not produce any morphological changes in the major organs and in the biochemical and hematological parameters of mice.
Asunto(s)
Animales , Masculino , Hojas de la Planta/química , Mikania/clasificación , Asteraceae/clasificación , /análisis , RatonesRESUMEN
The present study investigated the effects of phytol in pilocarpine-induced seizures. The latency for development of convulsions and mortality rate was recorded in this model using mice. The results revealed that phytol (25, 50 and 75 mg/kg, i.p.) increased latency to first seizure and decreased percentage of these seizures. Moreover, phytol also protected the animals against status epilepticus induced by pilocarpine, and decreased the mortality rate. Mice treated with pilocarpine (n=24) presented 100% of mortality during the first hour of observation. In turn, phytol-pretreated animals within 30 min before the administration of pilocarpine (400 mg/kg) remained alive during the first hour of observation. On the other hand, 6-8h after administration of pilocarpine it was observed that 10 (41.66%), 8 (33.33%) and 4 (16.66%) animals died (respectively). Thus, the pretreatment with phytol was able to block mortality rate during the first hour in acute phase of seizures, and significantly reduced this rate in a dose-dependent manner (p<0.05), suggesting an anticonvulsant effect. In addition, none of the phytol effects was blocked by pre-treatment with flumazenil, an antagonist of benzodiazepine receptors. In conclusion, phytol exhibits anticonvulsant activity by modulating of neurotransmitter systems, but further investigations are in progress to confirm this pharmacological property.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Fitol/uso terapéutico , Pilocarpina , Convulsiones/tratamiento farmacológico , Animales , Masculino , Ratones , Convulsiones/inducido químicamente , Convulsiones/mortalidad , Estado Epiléptico/inducido químicamente , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/mortalidad , Tasa de SupervivenciaRESUMEN
The effects of the protease inhibitors saquinavir, darunavir, ritonavir, and indinavir on growth inhibition, protease and phospholipase activities, as well as capsule thickness of Cryptococcus neoformans were investigated. Viral protease inhibitors did not reduce fungal growth when tested in concentrations ranging from 0.001 to 1.000 mg/L. A tendency toward increasing phospholipase activity was observed with the highest tested drug concentration in a strain-specific pattern. However, these drugs reduced protease activity as well as capsule production. Our results confirm a previous finding that antiretroviral drugs affect the production of important virulence factors of C. neoformans.
Asunto(s)
Antirretrovirales/farmacología , Cryptococcus neoformans/efectos de los fármacos , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Inhibidores de Proteasas/farmacología , Cryptococcus neoformans/enzimología , Cryptococcus neoformans/patogenicidad , Indinavir/farmacología , Ritonavir/farmacología , Saquinavir/farmacología , Factores de Virulencia/genéticaRESUMEN
The antioxidant activities of aqueous extract (AE) of Orbignya phalerata were assessed in vitro as well as its effect on locomotor activity and motor coordination in mice. AE does not possesses a strong antioxidant potential according to the scavenging assays; it also did not present scavenger activity in vitro. Following oral administration, AE (1, 2 and 3 g/kg) did not significantly change the motor activity of animals when compared with the control group, up to 24 h after administration and did not alter the remaining time of the animals on the Rota-rod apparatus. Further studies currently in progress will enable us to understand the mechanisms of action of the aqueous extract of Orbignya phalerata widely used in Brazilian flok medicine.
Asunto(s)
Arecaceae/química , Actividad Motora/efectos de los fármacos , Equilibrio Postural/efectos de los fármacos , Animales , Brasil , Desoxirribosa/metabolismo , Diazepam/farmacología , Depuradores de Radicales Libres/farmacología , Frutas/química , Hipnóticos y Sedantes/farmacología , Masculino , Medicina Tradicional , Ratones , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
A microplate assay and a thin-layer chromatography (TLC) "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL), Jatropha curcas (IC50 = 0.25 mg/mL), Jatropha gossypiifolia (IC50 = 0.05 mg/mL), Kalanchoe brasiliensis (IC50 = 0.16 mg/mL) and Senna alata (IC50 = 0.08 mg/mL). The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1% of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL) should be present.
Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Brasil , Inhibidores de la Colinesterasa/aislamiento & purificación , Cromatografía en Capa Delgada , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales/clasificaciónRESUMEN
A microplate assay and a thin-layer chromatography (TLC) "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL), Jatropha curcas (IC50 = 0.25 mg/mL), Jatropha gossypiifolia (IC50 = 0.05 mg/mL), Kalanchoe brasiliensis (IC50 = 0.16 mg/mL) and Senna alata (IC50 = 0.08 mg/mL). The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1 percent of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL) should be present.(AU)
Os ensaios de microplaca e cromatografia em camada delgada com base no ensaio de Ellman foram usados para triagem de inibidores da acetilcolinesterase dos extratos acetato de etila e metanol de plantas medicinais brasileiras de famílias que, segundo a literatura, tem usos tradicionais que podem estar relacionadas com a inibição da acetilcolinesterase, enzima associada ao mal de Alzheimer. Dezoito plantas das famílias: Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae e Rutaceae foram testadas. As espécies mais ativas foram Ipomoea asarifolia (CI50 = 0,12 mg/mL), Jatropha curcas (CI50 = 0,25 mg/mL), Jatropha gossypiifolia (CI50 = 0,05 mg/mL), Kalanchoe brasiliensis (CI50 = 0,16 mg/mL) e Senna alata (CI50 = 0,08 mg/mL). Os extratos mais promissores foram os das espécies Jatropha gossypiifolia e Senna alata, assumindo a presença de compostos com atividade semelhante à galantamina que deve conter cerca de 1 por cento de um composto ativo, ou se presentes em menores níveis ainda mais compostos ativos que a galantamina (CI50 = 0,37 x103 mg/mL) devem estar presentes.(AU)
Asunto(s)
Acetilcolinesterasa , Inhibidores de la Colinesterasa/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Brasil , Inhibidores de la Colinesterasa/aislamiento & purificación , Cromatografía en Capa Delgada , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales/clasificaciónRESUMEN
Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9 percent saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37 percent) and a decrease in taurine level (18 percent) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28 percent) and augmented taurine content (32 percent) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.
As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9 por cento (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram determinadas por HPLC. No hipocampo dos ratos do grupo pilocarpina foi observado um aumento significativo de 37 por cento na concentração de glutamato e uma diminuição de 18 por cento no nível de taurina, quando comparado ao grupo controle. O pré-tratamento com o antioxidante reduziu significativamente o nível de glutamato em 28 por cento e aumentou em 32 por cento os níveis de taurina no hipocampo dos ratos, quando comparado ao grupo pilocarpina. Nossos resultados sugerem que ocorrem alterações na concentração dos aminoácidos no hipocampo de ratos durante as convulsões induzidas por pilocarpina, e que o glutamato pode desempenhar um papel crucial na fisiopatologia das convulsões, e que o efeito protetor poderia ser alcançado com pré-tratamento com ácido lipóico, provavelmente pelo aumento da liberação ou redução da taxa de metabolização dos aminoácidos durante as convulsões.
Asunto(s)
Animales , Masculino , Ratas , Antioxidantes/farmacología , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Convulsiones/metabolismo , Taurina/metabolismo , Ácido Tióctico/farmacología , Cromatografía Líquida de Alta Presión , Hipocampo/química , Pilocarpina , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
Systemic injection of pilocarpine has been shown to induce recurrent seizures and epileptic discharges demonstrated by EEG monitoring. It also has been reported that antioxidants are able to diminish or prevent the occurrence of epileptic discharges induced by pilocarpine through the inhibition of free radical formation and neurotransmitter metabolic alterations. The purpose of this work was to determine the effects of lipoic acid (LA) on the levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and subsequent metabolites in the hippocampus of rats after seizure induction by pilocarpine. Seizures dramatically decreased the levels of DA, 5-hydroxyindoleacetic acid (5-HIAA) and NE, whereas significantly increased the levels of neurotransmitter metabolites. The administration of lipoic acid before seizure induction resulted in normalized levels of DA and 5-HA. However, the lipoic acid administration in similar conditions produced a reduction of the metabolites levels when compared with the pilocarpine group. These results suggest that the establishment of acute phase of seizures induced by pilocarpine might be produced by consequent the activation of serotonergic neurons. In addition, the lipoic acid inhibits hyperactivity of this system during the installation of pilocarpine-induced seizures.
Asunto(s)
Antioxidantes/farmacología , Monoaminas Biogénicas/metabolismo , Hipocampo/efectos de los fármacos , Pilocarpina , Convulsiones/tratamiento farmacológico , Ácido Tióctico/farmacología , Animales , Antioxidantes/uso terapéutico , Dopamina/metabolismo , Hipocampo/metabolismo , Ácido Hidroxiindolacético/metabolismo , Masculino , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Serotonina/metabolismo , Ácido Tióctico/uso terapéuticoRESUMEN
The short-term effects of pentoxifylline (PTX) on granulomatous lesions during Schistosoma mansoni infection in Swiss mice were evaluated. Drug administration was initiated 42 and 140 days post-infection (DPI) for the acute and chronic infection groups, respectively. Treatment was carried out daily with 200 mg/kg (subcutaneous route) of the drug for five consecutive days. Recovery of parasites and tissues was performed at 49 DPI and 147 DPI, respectively. Liver histological analysis showed a decrease in the inflammatory reaction and fibrous content of the granulomas studied, and a significant reduction (P < 0.001) in their mean diameter was observed in the groups of rodents treated with PTX in acute and chronic infection, when compared to their respective control groups. However, no alteration in the number of S. mansoni recovered from the portal system was observed, and egg-laying kinetics was not notably modified by PTX treatment, and the immature stage distribution of S. mansoni eggs showed minor intrinsic variations with no statistical differences in the parameter second-stage/female/g among untreated mice and treated mice in acute and chronic infections, respectively, when evaluated by intestinal oograms. Data obtained indicate probable immunomodulatory effects of PTX in murine schistosomiasis both in acute and chronic infection.