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

Grant number: 11/06704-4
Support Opportunities:Regular Research Grants
Duration: December 01, 2011 - May 31, 2014
Field of knowledge:Biological Sciences - Pharmacology - Ethnopharmacology
Principal Investigator:Marcos Hikari Toyama
Grantee:Marcos Hikari Toyama
Host Institution: Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TOYAMA, DANIELA O.; FERREIRA, MARCELO J. P.; ROMOFF, PAULETE; FAVERO, ORIANA A.; GAETA, HENRIQUE H.; TOYAMA, MARCOS H.. Effect of Chlorogenic Acid (5-Caffeoylquinic Acid) Isolated from Baccharis oxyodonta on the Structure and Pharmacological Activities of Secretory Phospholipase A2 from Crotalus durissus terrificus. BIOMED RESEARCH INTERNATIONAL, . (11/06704-4)
TOYAMA, DANIELA DE OLIVEIRA; GAETA, HENRIQUE HESSEL; TERASHIMA DE PINHO, MARCUS VINICIUS; PENA FERREIRA, MARCELO JOSE; ROMOFF, PAULETE; MATIOLI, FABIO FILIPPI; MAGRO, ANGELO JOSE; DE MATTOS FONTES, MARCOS ROBERTO; TOYAMA, MARCOS HIKARI. An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA(2) from Crotalus durissus terrificus. BIOMED RESEARCH INTERNATIONAL, . (12/06502-5, 13/12077-8, 11/06704-4)
PIRES, CAMILA L.; RODRIGUES, SELMA D.; BRISTOT, DANIEL; GAETA, HENRIQUE HESSEL; TOYAMA, DANIELA DE OLIVEIRA; LOBO FARIAS, WLADIMIR RONALD; TOYAMA, MARCOS HIKARI. Sulfated polysaccharide extracted of the green algae Caulerpa racemosa increase the enzymatic activity and paw edema induced by sPLA2 from Crotalus durissus terrificus venom. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 23, n. 4, p. 635-643, . (11/14241-4, 11/06704-4)

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