Bioprospection of novel anti-inflammatory molecules from natural Brazilian native products

Abstract

Anti-inflammatory medicines have commonly used to treat acute and chronic inflammatory process. However, because of its lower effectiveness and adverse effects, the development by medicines more selective and tolerable have been encouraged. These new alternatives must be able to modulate the inflammatory process in a different mechanism observed for available drugs in the market, for example leucocyte recruitment inhibition. Studies on natural products led to discovery of several clinically useful medicines, representing nearly 62% of all FDA approved medicines between 1981 to 2014. In the search for novel sources of bioactive molecules, natural products stands out for having compounds as flavonoids, isoflavones and others, which are indicated as promising anti-inflammatories and have been studied by our research group (FOP/UNICAMP e ESALQ/USP). In this context, two Brazilian natural products are noteworthy: the native fruits (FN) and organic propolis type 6 (PO6). Previous studies performed by our research group identified decreased leucocyte migration at inflammation site after treatment with FN and PO6, which shows the potential of these products as new sources of bioactive molecules. Thereby, we intent to investigate the phytochemical profile and bioprospect molecules from FN and PO6 which have neutrophil migration inhibitory activity in the inflammatory process. To carry out the bioguided study, PN and PO6 samples will be submitted to chemical process including extraction, fractionation, subfractionation using different chromatographic techniques, as well as the identification of bioactive compounds in their composition. Taken together, it will be conducted biological assays in vitro, in vivo and in silico to evaluation of anti-inflammatory activity of FN and PO6 extracts, fractions, subfractions of. The assays to be carry out include: NF-ºB activation and TNF-± release in macrophages culture; neutrophil migration of mice peritoneal cavity challenged; in silico study; analyses of cell secretome in vitro, in vivo intravital microscopy; cytokines levels and expression of adhesion molecules quantification in vivo. Therefore, this project is expected to identify anti-inflammatory compounds from Brazilian FN and PO6 which are capable to inhibit neutrophil migration and to elucidate its molecular mechanism of action. Furthermore, we expected that the scientific findings may support the sustainable use of these natural products and in the future the isolated compounds may be as prototype of novel anti-inflammatory drugs useful in dentistry and medical area, or a functional food that provide health and to prevent factor of risk to several inflammatory disease. (AU)