Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress.

Ana Amić,Jaime Rodríguez-Guerra Pedregal,Dejan Milenković,Denisa Mastiľák Cagardová,Marko Antonijević,Žiko Milanović,Zoran Marković,Jasmina M Dimitrić Marković

doi:10.3390/antiox10081303

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 Fe2+ 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.

Highlights

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1, it could be radical may strip the H-atom from the phenolic group a rate in the by OH radicals attacks
Little is known about the underlying mechanisms of skin protection by formulais known about the underlying mechanisms of protection by formulationsfrom fromUVA-mediated

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/As a protective barrier of the body, human skin is continuously exposed to solar UV radiation. Prolonged exposure may result in oxidative stress caused by radiation induced generation of reactive oxygen species (ROS, e.g., 1 O2 , • OH, O2 •− , O3 , and H2 O2 ). The main adverse health effects of UV radiation are premature skin aging, immune suppression, increased risks of skin cancer, and eye disorders and diseases [1,2].The hydroxyl radical (• OH) can be produced by solar ionizing radiation and UV radiations. High energy γ-rays and X-rays produce • OH by homolytic fission of water. Lower

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