RESUMO
BACKGROUND: Parkinson's disease (PD) is the most prevalent disease linked with age-associated neuronal degeneration. Phytotherapeutic compounds or agents have gained increased importance because of their increased specificity and minimal side effects. Isopulegol, a monoterpene, was utilized in the present study because of its wide range of therapeutic properties. Our aim was to examine the underlying mechanism of anti-neuroinflammatory action and neuroprotective efficacy of isopulegol in cell lines and in an experimental animal model of PD. METHODS: The MTT assay was performed in microglial BV-2 cells subjected to lipopolysaccharides (LPS). The release of NO and synthesis of ROS intracellularly in BV-2 cells were detected. C57BL/6 mice induced with MPTP were examined for motor function and coordination. Expression of proinflammatory mediators was also assessed both in vivo and in vitro. Histopathological sections of brain and expression of iNOS and COX-2 were also analyzed. RESULTS: BV-2 cells did not exhibit noticeable toxicity at selected concentrations and LPS-incubated cells showed marked elevation of NO levels and increased production of intracellular ROS. Increased expression of proinflammatory cytokines was also observed. Motor function and coordination deficits were observed in mice induced with MPTP. Histopathological abnormalities and increased iNOS and COX-2 expression were noted in MPTP-induced mice. Administration of isopulegol reversed the changes brought about by LPS and MPTP. CONCLUSION: The study indicated that isopulegol is a potential therapeutic drug against clinical complications of PD.
Assuntos
Monoterpenos Cicloexânicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Intoxicação por MPTP/tratamento farmacológico , Intoxicação por MPTP/genética , Intoxicação por MPTP/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Atividade Motora/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Doença de Parkinson/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
A novel, highly sensitive assay for quantitative determination of DNA is developed based on hybridization chain reaction (HCR) amplification and the separation via core-shell Fe3O4 polydopamine nanoparticles (Fe3O4@PDA NPs). In this assay, two hairpin probes are designed, one of which is labeled with a 6-carboxyfluorescein (FAM). Without target DNA, auxiliary hairpin probes are stable in solution. However, when target DNA is present, the HCR between the two hairpins is triggered. The HCR products have sticky ends of 24 nt, which are much longer than the length of sticky ends of auxiliary hairpins (6 nt) and make the adsorption much easier by Fe3O4@PDA NPs. With the addition of Fe3O4@PDA NPs, HCR products could be adsorbed because of the strong interaction between their sticky ends and Fe3O4@PDA NPs. As a result, supernatant of the solution with target DNA emits weak fluorescence after separation by magnet, which is much lower than that of the blank solution. The detection limit of the proposed method is as low as 0.05 nM. And the sensing method exhibits high selectivity for the determination between perfectly complementary sequence and target with single base-pair mismatch. Importantly, the application of the sensor for DNA detection in human serum shows that the proposed method works well for biological samples.
Assuntos
DNA/genética , Hibridização in Situ Fluorescente/instrumentação , Nanopartículas de Magnetita/química , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Análise de Sequência de DNA/instrumentação , Espectrometria de Fluorescência/instrumentação , Sequência de Bases , Técnicas Biossensoriais/instrumentação , DNA/análise , DNA/química , Enzimas , Desenho de Equipamento , Análise de Falha de Equipamento , Indóis/química , Nanopartículas de Magnetita/ultraestrutura , Dados de Sequência Molecular , Polímeros/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Three new complexes [Cd(4-pmpmd)1.5 (NO3)2] x CHCl3 (1), [Cd(3-pmpmd)1.5 (NO3)2] x EtOH (2), and [Zn(3-pmpmd)1.5 (NO3)2] x MeOH (3) (3- or 4-pmpmd = N,N'-bis(3- or 4-pyridylmethyl)pyromellitic diimide) containing T-shaped building blocks have been obtained from reactions between the long semirigid ligands 3- or 4-pmpmd and either cadmium or zinc nitrate. 1 forms noninterpenetrated 1D molecular ladders that are linked via multiple, complementary intermolecular C-H...O hydrogen bonds that effect the 3D alignment. 2 and 3 are isostructural and feature a noninterpenetrated 2D butterfly-shaped network with (6,3) topology. Multiple intermolecular C-H...O hydrogen bonds exist between the 2D layers and generate the 3D framework. The structural differences between 1 and 2 or 3 are attributed to the different conformations adopted by the ligands, which illustrate the influence of positional isomerism on the resultant supramolecular architectures of metal complexes.