Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production.

Resveratrol is a natural molecule with antioxidant action. Moreover, resveratrol is also considered to be a molecule with anti-inflammatory action, an effect attributed to suppression of prostaglandin (PG) biosynthesis. The aim of the present study was to investigate the effects of resveratrol, a polyphenol present in most red wines, on reactive oxygen species formation as well as on arachidonic acid (AA) release, cyclooxygenase expression, and PG synthesis in murine resident peritoneal macrophages. Results show that resveratrol exerted a strong inhibitory effect on superoxide radical (O2-) and hydrogen peroxide (H2O2) produced by macrophages stimulated by lipopolysaccharides (LPS) or phorbol esters (PMA). Resveratrol also significantly decreased [3H]AA release induced by LPS and PMA or by exposure to O2- or H2O2. Resveratrol treatment caused a significant impairment of cyclooxygenase-2 (COX-2) induction stimulated by LPS and PMA or by O2- or H2O2 exposure. These effects of resveratrol on [3H]AA release and COX-2 overexpression were correlated with a marked reduction of PG synthesis. Our results indicate that the antioxidant action of resveratrol affects AA mobilization and COX-2 induction.

[1]  J. J. Moreno,et al.  Influence of superoxide radical and hydrogen peroxide on arachidonic acid mobilization. , 1996, Archives of biochemistry and biophysics.

[2]  F. DeLeo,et al.  Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins , 1996, Journal of leukocyte biology.

[3]  J. Morrow,et al.  Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Lin,et al.  Inhibitory effects of phytopolyphenols on TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells. , 1997, Nutrition and cancer.

[5]  C. Hii,et al.  Activation of phospholipase A2 in human neutrophils by polyunsaturated fatty acids and its role in stimulation of superoxide production. , 1998, The Biochemical journal.

[6]  S. Renaud,et al.  Wine, alcohol, platelets, and the French paradox for coronary heart disease , 1992, The Lancet.

[7]  A. Waterhouse,et al.  Inhibition of human LDL oxidation by resveratrol , 1993, The Lancet.

[8]  J. Pezzuto,et al.  Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in Phorbol Ester-treated Human Mammary Epithelial Cells* , 1998, The Journal of Biological Chemistry.

[9]  C. Léger,et al.  alpha-tocopherol inhibits the respiratory burst in human monocytes. Attenuation of p47(phox) membrane translocation and phosphorylation. , 1998, The Journal of biological chemistry.

[10]  H. Hassan.  Determination of microbial damage caused by oxygen free radicals, and the protective role of superoxide dismutase. , 1984, Methods in enzymology.

[11]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[12]  L. W. Mapson.  Influence of halides on the oxidation of ascorbic acid: 2. Action of Cl on the cupric-cuprous system. , 1945, The Biochemical journal.

[13]  S. Urien,et al.  Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after red wine oral administration in rats. , 1996, International journal of clinical pharmacology research.

[14]  B. Babior.  The respiratory burst oxidase. , 1988, Hematology/oncology clinics of North America.

[15]  J. Tillement,et al.  Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. , 1996, International journal of tissue reactions.

[16]  D. Nathan,et al.  Quantitative nitroblue tetrazolium test in chronic granulomatous disease. , 1968, The New England journal of medicine.

[17]  E. Diamandis,et al.  Wines and grape juices as modulators of platelet aggregation in healthy human subjects. , 1996, Clinica chimica acta; international journal of clinical chemistry.

[18]  L. Barrier,et al.  Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro tests. , 1997, Life sciences.

[19]  J. J. Moreno,et al.  Induction by interleukin-1beta peptide of prostaglandin E2 formation via enhanced prostaglandin H synthase-2 expression in 3T6 fibroblasts. , 1998, Biochemical pharmacology.

[20]  E. Diamandis,et al.  The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[21]  L. W. Mapson.  The influence of halides on the oxidation of ascorbic acid. , 1941, The Biochemical journal.

[22]  M. Dunn,et al.  Physiology of the mesangial cell. , 1989, Physiological reviews.

[23]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[24]  J. J. Moreno,et al.  Role of prostaglandin H synthase-2-mediated conversion of arachidonic acid in controlling 3T6 fibroblast growth. , 1997, The American journal of physiology.

[25]  W. Dercks,et al.  The significance of stilbene phytoalexins in the Plasmopara viticola-grapevine interaction , 1989 .

[26]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.