Avaliação da atividade osteogênica e antidipogênica de polissacarídeos sulfatados de macroalgas marinhas verdes

The sulfated polysaccharides (SP) of seaweeds are highly complex and heterogeneous macromolecules that have shown diverse activities, including in the modeling of osteogenic and adipogenic differentiation. Thereafter, these molecules have been studied in the scope of regenerative medicine for the...

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Autor principal: Chaves Filho, Gildacio Pereira
Outros Autores: Moreira, Susana Margarida Gomes
Formato: doctoralThesis
Idioma:pt_BR
Publicado em: Universidade Federal do Rio Grande do Norte
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Endereço do item:https://repositorio.ufrn.br/handle/123456789/47048
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Resumo:The sulfated polysaccharides (SP) of seaweeds are highly complex and heterogeneous macromolecules that have shown diverse activities, including in the modeling of osteogenic and adipogenic differentiation. Thereafter, these molecules have been studied in the scope of regenerative medicine for the development of alternative therapies to overcome diseases related to bone metabolism and obesity. Among the SP, those derived from green seaweeds are the least studied and, therefore, in this work, the osteogenic and antiadipogenic activity of SPcontaining samples from Caulerpa prolifera and Caulerpa sertularioides were investigated. As an essential part of biocompatibility evaluation of new molecules, the genotoxicity of samples with biological activity was also studied. Several reviews describe the multiple bioactivities of SP from seaweeds, however, regarding their osteogenic activity, there is no consensus on how to use them and their real effectiveness in this process. Therefore, in this study, a systematic review was carried out to answer the question “Do SP from seaweeds promote osteogeniesis?”. The results of this review show that SP from seaweeds effectively promote an increase in osteogenic markers (alkaline phosphatase and extracellular matrix mineralization), indicating that they can be considered for application in bone regeneration. The experimental results obtained with the treatment of human stromal stem cells with SP-containing samples of C. prolifera and C. sertularioides, at non-cytotoxic concentrations (<10 µg/mL), showed an increase in osteogenic markers. Under these conditions, no genotoxic effect was observed. It was also shown that one fraction containing PS isolated from C. prolifera inhibited adipogenic differentiation of 3T3L1 pre-adipocytes, at non-cytotoxic concentrations (<200 µg/mL), reducing the accumulation of total lipids and triglycerides in the C. elegans. Surprisingly, it was possible to refine the purification of C. sertularioides samples, using ion exchange chromatography, and one SP-rich subfraction, with greater antiadipogenic effect, was obtained. Thus, the antiadipogenic effect was achieved using a significantly lower sample concentration (50 µg/mL) than those reported in the literature. Together, the results highlight the potential of SP for application in the development of alternative therapies for problems related to bone regeneration and obesity.