Characterization of anti-phospholipase A2 activity and evaluation of potential anti-inflammatory of natural and modified special metabolites from plants

Abstract

The therapeutic potential of medicinal plants is traditionally assigned to classes of chemical constituents, called special metabolites: flavonoids, alkaloids, terpenes and others. Natural compounds, quercetin, rutin and betulin have been studied and showed inhibitory activity against selective sPLA2, before these promising results increases the interest to search for other molecules that have anti-sPLA2 activity. Many of these studies use as models the sPLA2 purified from snake venoms, which have a similar structure and function to human sPLA2 (shPLA2). Project aims is to evaluate the effects of flavonoids, terpenoids, sapogenins and pterocarpans natural and chemically modified on the genesis of arachidonic acid and consequently the inflammatory process induced by catalytically active sPLA2s isolated from venom of Crotalus durissus terrificus and Bothrops jararacussu. The anti-inflammatory activity is determined by the ability of substances to reduce or totally inhibit inflammatory activity and/or enzymatic of sPLA2. The techniques to be used in this project: two enzymatic assay using synthetic chromogenic substrates, chromatographic analytical testing, spectroscopic studies of UV-Vis, DAD, fluorescence, circular dichroism, mass spectrometry and microsequencer that will allow to locate potential structural changes in the sPLA2 treated by the compounds. The molecular modeling and X-ray crystallography will be used to evaluate the specific regions of interaction between protein and compounds. The structural studies will be accompanied by pharmacological tests: paw edema and skin, mast cell degranulation and platelet aggregation as well as trials of molecular biology, which enable the integration of the structural results with the functional sPLA2. (AU)