RESUMO
Infections caused by Trichomonas vaginalis in humans are one of the main public health problems caused by sexually transmitted diseases. Objective of this study was to evaluate potential biological activity of the medicinal plant Argemone mexicana (Mexican poppy) on T. vaginalis. Methanolic extracts of the stems and leaves of A. mexicana, and different fractions were prepared with solvents of different polarities. The extracts and functional groups were detected containing sterols, triterpenes, quinones, flavonoids and, alkaloids. Extracts from both the stems and leaves of A. mexicana inhibited the growth of T. vaginalis with half-maximal inhibitory concentration value of 70.6 and 67.2 µg/ml, respectively. In the active fractions, the most abundant compounds were berberine and jatrorrhizine, with presumed antiparasitic activity.
Assuntos
Extratos Vegetais/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/crescimento & desenvolvimento , Protocolos de Quimioterapia Combinada Antineoplásica , Vacinas Bacterianas , Ciclofosfamida , Depressão Química , Relação Dose-Resposta a Droga , Doxorrubicina , Fluoruracila , Técnicas In Vitro , Leucovorina , Metanol , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química , Quinonas , Esteróis , TriterpenosRESUMO
The misfolding of protein and its assembly into amyloid fibrils with a characteristic ß-sheet-rich secondary structure, cause a lot of illnesses. Polyphenols have been extensively studied as a class of amyloid inhibitors, whose effect depends on the position and number of hydroxyl groups around the flavone backbone. In this study, we used bovine serum albumin (BSA) as an amyloid model to test the anti-amyloid effects of Avenanthramide-C (Avn-C), a molecule with a long aliphatic linker between two aromatic rings. We used spectroscopy techniques like thioflavin T fluorescence and circular dichroism, to follow the ß-sheet-rich aggregates of BSA upon incubation at 68 °C. Our results demonstrated that Avn-C shows higher inhibitory effect on BSA oligomerization at micromolar concentrations, than Epigallocatechin gallate (EGCG) and Curcumin, proving for the first time, that Avn-C can serve as potential molecule in preventing protein aggregation.
Assuntos
Amiloide/biossíntese , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/prevenção & controle , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , ortoaminobenzoatos/farmacologia , Animais , Bovinos , Estrutura Molecular , ortoaminobenzoatos/químicaRESUMO
Due to the biological activities of Syzygium aromaticum essential oil, its incorporation in methacrylate polymeric (Eudragit E100) nanoparticles (NP), physical characterization, and antimicrobial essays were evaluated. The clove bears great potential for applications in dentistry. The oil was obtained by hydrodistillation and oil loaded NP using the nanoprecipitation method. Particle size and polydispersity index were determined by photon correlation spectroscopy, and physical morphology by electron microscopy. Loading capacity and in vitro eugenol release were evaluated by gas mass chromatography, and the antimicrobial activity of oil loaded-NP was calculated against Streptococcus mutans. Different chemical ingredients were characterized, and eugenol was the principal compound with 51.55%. Polymer content was directly related to NP homogenous size, which was around 150 nm with spherical morphology. A 73.2% loading capacity of eugenol was obtained. Oil loaded NP presented a fickian-type release mechanism of eugenol. Antimicrobial activity to 300 µg/mL was obtained after 24 h.
Debido a las actividades biológicas del aceite esencial de Syzygium aromaticum, se evaluó su incorporación en nanopartículas (NP) de metacrilato polimérico (Eudragit E100), su caracterización y ensayos antimicrobianos. El clavo tiene un gran potencial para aplicaciones en odontología. El aceite se obtuvo por hidrodestilación y las NP cargado de aceite utilizando el método de nanoprecipitación. El tamaño de partícula y el índice de polidispersidad se determinaron mediante espectroscopia de correlación fotónica y su morfología por microscopía electrónica. La capacidad de carga y la liberación de eugenol in vitro se evaluaron mediante cromatografía de gases en masa, y la actividad antimicrobiana se evaluó contra Streptococcus mutans. Se caracterizaron diferentes ingredientes químicos, siendo el eugenol el principal compuesto con 51.55%. El contenido de polímero se relacionó directamente con el tamaño homogéneo de NP, que fue de alrededor de 150 nm con morfología esférica. Se obtuvo un 73,2% de capacidad de carga de eugenol. El aceite cargado en NP presentó un mecanismo de liberación de eugenol de tipo fickiano. La actividad antimicrobiana a 300 µg/mL se obtuvo después de 24 h.
Assuntos
Polímeros/química , Óleos Voláteis/administração & dosagem , Syzygium/química , Nanopartículas/química , Antibacterianos/administração & dosagem , Streptococcus mutans/efeitos dos fármacos , Eugenol/farmacologia , Óleos Voláteis/farmacologia , Administração Oral , Cromatografia em Camada Fina , Sistemas de Liberação de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Antibacterianos/farmacologiaRESUMO
Alpha-synuclein (α-syn) is an intrinsically-disordered protein that has been associated with Parkinson's disease through its deposition in an amyloid fibril form within Lewy Body. Several lines of evidence suggest that the physical association of α-syn with the mitochondrial membranes may cause membrane damage and mitochondrial dysfunction, playing an important role in disease progression. Although there is strong evidence that the N-terminus part of α-syn is essential for membrane affinity, cooperative formation of helical domains and regulation of mitochondria membrane permeability, the amino acids involve in this membrane binding is still controversial. Fluorescence spectroscopy, circular dichroism and Langmuir monolayer technique were used to elucidate this recognition process of mitochondrial membrane system by synthetic peptides derived from α-syn N-terminal segment. The results obtained in this work show that the first 15 amino acid of the α-syn N-terminal segment mainly participate in the anchoring, perturbing the membrane hydrophobic region, while the peptide corresponding to 16-30 residues interacts only with the phospholipid polar headgroup, confirming that the binding affinity of the N-terminus is nonuniform.
Assuntos
Membranas Mitocondriais/metabolismo , alfa-Sinucleína/metabolismo , Sequência de Aminoácidos , Ligação Proteica , alfa-Sinucleína/químicaRESUMO
Since the introduction of bone morphogenetic proteins, their use has become an invaluable ally for the treatment of bone defects. These proteins are potent growth factors, related to angiogenic and osteogenic activity. The osteoinductive capacity of recombinant bone morphogenetic protein (rhBMP) in the formation of bone and cartilage has been confirmed in in vitro studies and evaluated in clinical trials. To obtain a therapeutic effect, administration is systemic, by injection over the physiological dose. Among the disadvantages, ectopic bone formation or high morbidity in cases of spinal fusion is observed. In this review, the roles of bone morphogenetic proteins in bone repair and clinical applications are analyzed. These findings represent advances in the study of bone regeneration and application of growth factors for more predictable results.
Assuntos
Doenças Ósseas/terapia , Proteínas Morfogenéticas Ósseas/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Doenças Ósseas/patologia , Proteínas Morfogenéticas Ósseas/efeitos adversos , Humanos , Injeções , Ossificação Heterotópica/induzido quimicamente , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Fusão Vertebral/métodosRESUMO
La enfermedad de Parkinson es un desorden neurodegenerativo común originado por la muerte celular dentro de la substancia nigra pars compacta. Se caracteriza por la presencia de agregados intracelulares proteicos compuestos principalmente por la alfa-sinucleína. Aunque los mecanismos moleculares por los cuales esta proteína contribuye a la toxicidad neuronal todavía se desconocen, se ha sugerido que los intermediarios oligoméricos son citotóxicos y permeabilizan las membranas celulares posiblemente a través de complejos que forman un poro en la bicapa; sin embargo, este mecanismo es altamente controversial. Así pues es necesario identificar el mecanismo por el cual ocurre la permeabilización de membranas para entender la interacción entre oligómeros y lípidos y poder estimar la relevancia biológica de este proceso.En este trabajo se evaluó por espectroscopía de fluorescencia la liberación de contenidos acuosos originados por oligómeros de alfa-sinucleína desde vesículas fosfolipídicas de distinta composición mediante el método ANTS/DPX. Los resultados muestran que la disrupción de membranas solo ocurre en presencia de lípidos aniónicos y también por parámetros de empaquetamiento lipídico, lo que sugiere que la accesibilidad a la región hidrofóbica de las vesículas modula la interacción lípido-oligómero.
Parkinson's disease is a common neurodegenerative disorder marked by increased cell death within the substantia nigra pars compacta. It is characterized by the presence of intracellular aggregates composed primarily of the protein alpha-synuclein. How the aggregation of a-synuclein is related to neuronal degeneration is an important unresolved question. Oligomeric intermediates have been found to be more toxic to cells than monomeric or fibrillar forms of the protein. A possible mechanism by which oligomers could be toxic is through the disruption and permeabilization of cellular membranes. The proposed disruption mechanism is the formation of pore-like structures within the lipid bilayer although this mechanism is still highly controversial. To identify the mechanism through which membrane permeabilization is facilitated and to estimate the biological relevance of this process, it is crucial to have a greater knowledge of the lipid-oligomer interaction. The membrane disruptive effect of Alpha-synuclein oligomers on lipid vesicles of different headgroup composition using the ANTS/DPX assay was evaluated in this work. It was shown that membrane permeabilization is mainly determined by the presence of negatively charged lipids and also by lipid packing parameters, suggesting that the accessibility to the bilayer hydrocarbon core modulates oligomer-membrane interaction.
pars compacta. é caracterizada pela presença de agregados intracelulares protéicos compostos especialmente pela alfa-sinucleína.Mesmo que se desconheça os mecanismos moleculares por onde essa proteína contribui para toxicidade neuronal, existe uma possibilidade de que os intermediários oligoméricos sejam citotóxicos, e permeabilizam as membranas celulares possivelmente através de complexos que formam um poro na capa dupla, entretanto, este mecanismo gera muita controvérsia. Sendo assim, é necessário identificar o mecanismo responsável pela permeabilidade das membranas para entender a interação entre os oligômeros e os lipídios, e para ter uma estimativa da relevância biológica deste processo. Neste trabalho, analisamos através de espectroscopia de fluorescência, a liberação dos conteúdos aquoso originados por oligômeros de alfa-sinucleína a partir das vesículas fosfolídicas de composição diferente através do método ANTS/DPX. Os resultados mostraram que a ruptura de membranas ocorrerá somente diante da presença de lipídios aniônicos, e também pelos parâmetros de empacotamento lipídico, e isso sugere que a acessibilidade à região hidrofóbica das vesículas faz a modulação da interação lípidio-oligômero.
Assuntos
Humanos , alfa-Sinucleína , Doença de Parkinson , Membrana CelularRESUMO
La enfermedad de Parkinson es un desorden neurodegenerativo común originado por la muerte celular dentro de la substancia nigra pars compacta. Se caracteriza por la presencia de agregados intracelulares proteicos compuestos principalmente por la alfa-sinucleína. Aunque los mecanismos moleculares por los cuales esta proteína contribuye a la toxicidad neuronal todavía se desconocen, se ha sugerido que los intermediarios oligoméricos son citotóxicos y permeabilizan las membranas celulares posiblemente a través de complejos que forman un poro en la bicapa; sin embargo, este mecanismo es altamente controversial. Así pues es necesario identificar el mecanismo por el cual ocurre la permeabilización de membranas para entender la interacción entre oligómeros y lípidos y poder estimar la relevancia biológica de este proceso. En este trabajo se evaluó por espectroscopía de fluorescencia la liberación de contenidos acuosos originados por oligómeros de alfa-sinucleína desde vesículas fosfolipídicas de distinta composición mediante el método ANTS/ DPX. Los resultados muestran que la disrupción de membranas solo ocurre en presencia de lípidos aniónicos y también por parámetros de empaquetamiento lipídico, lo que sugiere que la accesibilidad a la región hidrofóbica de las vesículas modula la interacción lípido-oligómero.(AU)
Parkinsons disease is a common neurodegenerative disorder marked by increased cell death within the substantia nigra pars compacta. It is characterized by the presence of intracellular aggregates composed primarily of the protein alpha-synuclein. How the aggregation of a-synuclein is related to neuronal degeneration is an important unresolved question. Oligomeric intermediates have been found to be more toxic to cells than monomeric or fibrillar forms of the protein. A possible mechanism by which oligomers could be toxic is through the disruption and permeabilization of cellular membranes. The proposed disruption mechanism is the formation of pore-like structures within the lipid bilayer although this mechanism is still highly controversial. To identify the mechanism through which membrane permeabilization is facilitated and to estimate the biological relevance of this process, it is crucial to have a greater knowledge of the lipid-oligomer interaction. The membrane disruptive effect of Alpha-synuclein oligomers on lipid vesicles of different headgroup composition using the ANTS/DPX assay was evaluated in this work. It was shown that membrane permeabilization is mainly determined by the presence of negatively charged lipids and also by lipid packing parameters, suggesting that the accessibility to the bilayer hydrocarbon core modulates oligomer-membrane interaction.(AU)
A doenþa de Parkinson é uma condiþÒo neuro-degenerativa comum que se origina na morte celular dentro da substÔncia nigra pars compacta. é caracterizada pela presenþa de agregados intracelulares protéicos compostos especialmente pela alfa-sinucleína.Mesmo que se desconheþa os mecanismos moleculares por onde essa proteína contribui para toxicidade neuronal, existe uma possibilidade de que os intermediários oligoméricos sejam citotóxicos, e permeabilizam as membranas celulares possivelmente através de complexos que formam um poro na capa dupla, entretanto, este mecanismo gera muita controvérsia. Sendo assim, é necessário identificar o mecanismo responsável pela permeabilidade das membranas para entender a interaþÒo entre os olig¶meros e os lipídios, e para ter uma estimativa da relevÔncia biológica deste processo. Neste trabalho, analisamos através de espectroscopia de fluorescÛncia, a liberaþÒo dos conteúdos aquoso originados por olig¶meros de alfa-sinucleína a partir das vesículas fosfolídicas de composiþÒo diferente através do método ANTS/DPX. Os resultados mostraram que a ruptura de membranas ocorrerá somente diante da presenþa de lipídios ani¶nicos, e também pelos parÔmetros de empacotamento lipídico, e isso sugere que a acessibilidade O regiÒo hidrofóbica das vesículas faz a modulaþÒo da interaþÒo lípidio-olig¶mero.(AU)