Abstract
In this work we have characterized the action of the naringin, a flavonoid found in grapefruit and known for its various pharmacological effects, which include antioxidant, blood lipid lowering and anticancer activity, on the structure and biochemical activities of a secretory phospholipase A (sPLA2) from Crotalus durissus cascavella, an important protein involved in the releasinge of arachidonic acid in phospholipid membranes. sPLA2 was incubated with naringin (mol:mol) at 37 °C and a discrete reduction in the UV scanning signal and a modification of the circular dichroism spectra were observed after treatment with naringin, suggesting modifications of the secondary structure of the protein. This flavonoid was able to decrease enzymatic activity and some pharmacological effects, such as myonecrosis, platelet aggregation, and neurotoxic activity caused by sPLA2, however, the inflammatory effect was not affected by naringin. In addition, small angle X-ray scattering (SAXS) data were collected for sPLA2 and naringin-treated sPLA2 to evaluate possible modifications of the protein structure. These structural investigations have shown that sPLA2 is an elongated dimer in solution and after treatment with naringin a conformational change in the dimeric configuration was observed. Our results suggest that structural modification may be correlated with the loss of enzymatic activity and alterations in pharmacological properties.
Highlights
Polyphenolic compounds, such as flavonoids and coumarins, are widely distributed in the plant kingdom
Because sPLA2 from snake venom has been characterized as a proinflammatory inducer, we investigated for the first time the effect of naringin on the edematogenic activity of sPLA2 from Crotalus durissus cascavella venom and evaluated other biological and pharmacological activities induced by this protein
Amino acid analysis indicated that naringin mainly induced modification on the aromatic amino acid residues and histidines, similar to what was reported in a previous study with morin [7]
Summary
Polyphenolic compounds, such as flavonoids and coumarins, are widely distributed in the plant kingdom. Hesperidin, and neohesperidin have been described as some of the most abundant flavanones found in the Citrus genus, and are responsible for many of the pharmacological properties of Citrus flavonoids These flavanones are interesting because of their antitumoral and anti-inflammatory effects, which are linked to the abilities of these compounds to inhibit enzymes involved in cell activation [14]. Only a few reports have been published regarding SAXS analysis of PLA2 [20,21] In these studies, two different oligomeric states were observed for sPLA2s in solution: monomeric for sPLA2 from. Electrophoresis and spectroscopic studies have suggested that the dimer-like structure in solution is common to sPLA2s from other snake venoms [22,23]. The low resolution model obtained for sPLA2-Nar presents an interesting bending in comparison with the envelopes for the native sPLA2 that seem to be correlated with the enzymatic and pharmacological alterations observed in our studies
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