Abstract
Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of (•)OH generation. The resulting FA phenoxyl radical, after the scavenging of a second (•)OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe(2+) ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of (•)OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.