Resveratrol, Tyrosol and Their Derivatives Inhibit Platelet Activating Factor Biosynthetic Enzymes in Homogenized U-937 Cells

Abstract

Platelet activating factor (PAF) is a potent lipid mediator involved in inflammation, among other pathophysiological conditions. Bioactive compounds from foods have been suggested to suppress inflammation as well as regulate PAF biosynthesis. Phenolics, such as resveratrol and tyrosol, and their acetylated derivatives, inhibited PAF biosynthetic enzymes’ activity, namely acetyl-coenzyme A: lyso–platelet-activating factor acetyltransferases (lysoPAF-AT), and 1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) under inflammatory stimuli. This study investigates whether resveratrol and tyrosol lipophilic derivatives are capable of affecting the activity of the two isoforms of lysoPAF-AT along with the activity of PAF-CPT compared with the initial compounds under basal conditions. The derivatives were chemically synthesized and the experiments were conducted either with or without pre-incubation of homogenized U-937 cells and the phenolics and the enzyme activities were determined. Pre-incubation experiments resulted in lower half inhibitory concentration (IC₅₀) than those without pre-incubation, reaching a 5-fold difference between them. Moreover, there were differences among parent compounds and their derivatives, suggesting a dependence on the differently substituted groups of the phenolics. PAF-CPT tends to be less phenolic structure dependent than lysoPAF-ATC, whereas the other isoform, lysoPAF-ATE, was less sensitive in general. Resveratrol and its derivatives were more potent than the tyrosolic compounds, regardless of the enzyme test or the conditions of the experiment. The use of phenolic lipophilic derivatives in pharmaceuticals and in food preparation may overcome the limitations of natural phenolics with regard to their weak solubility and stability in a lipophilic environment.