Navegando por Assunto "Swietenia macrophylla"
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Item Acesso aberto (Open Access) Avaliação do potencial biotecnológico de compostos isolados de Swietenia macrophylla no tratamento de câncer(Universidade Federal do Pará, 2015-11-30) BARRETO, Leilane de Holanda; MONTENEGRO, Raquel Carvalho; http://lattes.cnpq.br/0043828437326839Swietenia macrophylla (mahogany) is a species of plant widely known for its therapeutic potential. The main constituents isolated extracts of this plant are structures known as limonoids. The limonoids also have several biological activities, among them, antitumor activity. The aim of this study was to evaluate the antitumor potential of the extract and limonoid obtained from leaves of S. macrophylla in cancer cell lines. Cytotoxicity to 5 cancer cell lines and normal revealed that the extract had cytotoxic effect in colorectal cancer cell lines (HCT-116 and HT-29), as the limonoids were cytotoxic for colorectal cancer (HCT-116) and melanoma (SKMEL-19). Given these results, we selected the limonoid L3 and HCT-116 cell line to evaluate the mechanism of action, as well as the HT-29 lineage, which has the TP53 gene mutated for comparison as possible of the compound mechanism of action, once it was less sensitive to L3. Moreover, L3 showed more selective for tumor cells. None of the compounds caused hemolysis of erythrocytes in mice. To evaluate the antiproliferative action of L3, the clonogenic assay was performed, where the two lines there was a significant reduction of colonies, however this reduction was more significant in HCT-116. The L3 compound also has caused death by apoptosis in a dose-dependent manner in the lines, where the number of cells in apoptosis was higher in HCT-116. To evaluate DNA damage, it was held the comet assay, which showed that L3 cause damage to the DNA of the two cancer cell lines, with greater damage index in HCT-116. The assessment of cell cycle distribution of cells after treatment with L3 showed that there was blocking the cycle at the G2 / M phase, mainly in HCT-116 (45% of the cells). From these data, it conducted a study of genes involved in this phase of the cycle, from analysis of their expression by RT-PCR. The ATM gene, which is activated by DNA damage activates the CHK-2 which in turn phosphorylates p53 protein. p53 protein can activate the transcription of p21 gene, which triggers cell cycle stopped, or activate cell death pathways. In this study, we found increased expression of genes ATM, CHK-2, TP53, ARF in a dose dependent in both cacer cell lines, and this expression was higher in HCT-116 cell line. The expression of p21 was increased in HCT-116, while in HT-29 decreased, this is due to the fact that HT-29 possess the mutant TP53 gene, then your protein does not work properly. As the path of apoptosis was evaluated caspase-3 gene and the anti-apoptotic gene BCL-2. There was increase in the expression of caspase-3 mainly in HCT-116 and decrease of BCL-2. These results suggest that L3 may be causing damage to the DNA of cells, triggering a cellular signaling pathway dependent on p53. To evaluate the toxicity of S. macrophylla extract, it was held the acute toxicology testing in mice, where the extract did not cause any changes in the physiological parameters of animals. As the claustogenicidade test (micronucleus) also showed that the extract is not mutagenic in the mouse bone marrow cells.Item Acesso aberto (Open Access) Caracterização dos efeitos do extrato de folhas de Swietenia macrophylla em modelo experimental de doença de Parkinson(Universidade Federal do Pará, 2014-02-13) LIMA, Natália Pontes; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978Previous studies indicate that the leaf extract of Swietenia macrophylla has abundant antioxidants in its chemical composition with neuroprotective effects in culture. One of the main mechanisms involved in neurodegeneration of Parkinson's disease (PD) is oxidative stress. Therefore, antioxidants are potential candidates for therapies aiming to slow the neurodegenerative process of the disease. This study aims to characterize the effects of the S.macrophylla leaf extract regrading the nigrostriatal degeneration and behavioral changes in mice exposed to a single unilateral injection of 6-OHDA in the striatum. Male mice were used, which underwent stereotactic surgery andwere injected 20 μg of 6-OHDA in the left striatum. The animals were divided into 4 groups according to the dose of mahogany extract administered. The extract was administered intraperitoneally in the first 7 days after injection of 6-OHDA at the doses of 0.0 (control) 0.5 (G1), 1.0 (0G2) and 5.0 mg/kg (G3). The control group (CG) received 0.9% saline (vehicle). Ambulation analysis in the open field was performed before, on the 7th and 21th days post-surgery and the number of apomorphine-induced rotations, in the 7th and 21th days after surgery. Evaluation of the neurodegeneration was performed by counting TH+ dopaminergic neurons in the substantia nigra by stereology. As a result, we found a statistically significant difference at day 21, where G2 and G3 showed a reduction in the ambulatory behavior in relation to G1 and GC; the latter two groups showed equivalent behavior. by, At day 21, G1 had significantly lower average apomorphine-induced rotations than GC, G2 and G3. In cell counts, G1 presented statistically significant reduction of the dopaminergic neurons loss compared to control. Thus, we conclude that the leaf extract of S.macrophylla in the concentration of 0.5 mg/kg provided neuroprotection for the nigrostriatal system neurodegeneration induced by 6-OHDA.Item Acesso aberto (Open Access) Efeito do extrato aquoso de folhas de mogno (Swietenia macrophylla) em modelo in vivo de doença de Parkinson com lesão com 6-hidroxidopamina(Universidade Federal do Pará, 2012-09-28) RAMOS, Luciana Fernandes Pastana; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra and the presence of classical clinical signs bradykinesia, muscle rigidity, resting tremor and postural instability. The etiology is still unknown and the available treatment options only promote relief of symptoms. Experimental models of PD are fundamental for studies aiming to identify the molecular events involved in the disease and to discover new neuroprotective therapies. This study used a hemiparkinsonism model with lesion induced by 6-hydroxydopamine (6-OHDA), and investigated effects of an aqueous extract of leaves of mahogany (Swietenia macrophylla) on the dopaminergic neurons of the substantia nigra pars compacta (SNpc) and on behavioural parameters assessed in the open-field and apomorphine-induced rotacional tests. The results showed that the 6-OHDA lesioned animals exhibited contralateral rotation induced by apomorphine and significant reduction of dopaminergic neurons in SNpc. However, only 6-OHDA lesioned animals treated with mahogany extract showed significant decrease in relation to the group vehicle/vehicle. There was also a significant decrease in ambulation and rearing in the group 6-OHDA/mahogany. In conclusion, the mahogany extract under the conditions used in the present study potentiated the cytotoxic effect of 6-OHDA and yet promoted worsening of behavioral parameters of the animals.