Resveratrol Inhibits the Activity of Equine Neutrophil Myeloperoxidase by a Direct Interaction with the Enzyme

Abstract

Resveratrol is a polyphenolic antioxidant present in beverage and food known for its multiple protective effects. We report the inhibitory effects of resveratrol on equine myeloperoxidase (MPO), a hemic peroxidase present in the granules of the neutrophils involved in the inflammatory response. Resveratrol inhibited the production of reactive oxygen species (ROS) by stimulated equine neutrophils by acting as a direct scavenger of the ROS released by the cells but did not modify the degranulation of the stimulated neutrophils as the amounts of released MPO were unchanged. Resveratrol strongly inhibited the chlorination, oxidation, and nitration activities of MPO in a dose-dependent manner. By an original technique of specific immunological extraction followed by enzymatic detection (SIEFED), we demonstrated that resveratrol inhibited the peroxidasic activity of the MPO measured by a direct interaction such as the fixation of resveratrol on the enzyme. The observation of a decrease of the accumulation of compound II suggested that resveratrol acts as an electron donor for MPO reduction.

Modulatory activities of Agelanthus dodoneifolius (Loranthaceae) extracts on stimulated equine neutrophils and myeloperoxidase activity

“…The greatest inhibitory effect that was obtained with the ethyl acetate and diethyl ether fractions could be correlated with their high phenolic contents and better extraction of polyphenolic compounds. Several studies have reported that phenolic compounds such as gallic acid, curcumin, resveratrol and myricitrin are effective substrates and inhibitors of MPO (8,9,(44)(45)(46). In our study, we confirmed the inhibitory activities of gallic acid and quercetin.…”

“…However, in some conditions involving acute and chronic inflammation, MPO is released from the cells and can cause severe damage to macromolecules in the cell membranes and extracellular space (7). Thus, inhibiting the enzymatic activity of MPO or decreasing the oxidant activity of PMNs may prove beneficial for the treatment of inflammation-related diseases (8,9). The use of traditional medicine is widespread and plants have long been used in folk medicine for the treatment of chronic inflammatory processes.…”

Resveratrol: A multitargeted agent for age-associated chronic diseases

“…3). Resveratrol has been shown to interact with protein kinase C, 10 aromatase, 11 hetero-dimeric alphaVbeta3 integrin, 12 multidrug resistance protein 1, 13 β-lactoglubulin, 14 human serum albumin, 15 human DNA topoisomerase II, 16 plasma lipoprotein, 17 nucleic acids, 18 DNA polymerase α and δ, 19 myeloperoxidase, 20 tubulin, 21 estrogen receptor α and β, 22 F1-ATPase, 23 sulfonyl urea receptors, 24 cytosolic alcohol dehydrogenase, 25 amyloid fibrils 26 and dihydronicotinamide riboside quinone reductase 2 (NQO2). 27 In most cases interaction of resveratrol with these proteins leads to inactivation of the molecule.…”

Inhibition by Polyphenolic Phytochemicals and Sulfurous Compounds of the Formation of 8-Chloroguanosine Mediated by Hypochlorous Acid, Human Myeloperoxidase, and Activated Human Neutrophils

“…Polyphenolic compounds inhibit the activity of MPO by interaction of the compound with the active site of the enzyme. [27][28][29] The explanation of the inhibitory action shown by catechins in this study is unknown, and further study is needed.…”

“…The synthesis of NOX and MPO, and ROS generation in activated neutrophils have been reported to be affected by certain polyphenols. 2,23,27,28,[30][31][32] Accordingly, the suppression of MPO-and activated neutrophilinduced chlorination of Guo shown by plant polyphenols must relate to the actions of NOX or MPO. These phenomena might have to do with the reduction of neutrophil functioning as in respiratory burst, ROS production, MPO release, and the assembly of enzymes by phenolic compounds.…”