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

Antioxidants

Ana Amić¹  Dejan Milenković²  Žiko Milanović²  Zoran Marković²  Marko Antonijević²  Jasmina M. Dimitrić Marković³  Jaime Rodríguez-Guerra Pedregal⁴  Denisa Mastiľák Cagardová⁵ 

[1]Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Ulica cara Hadrijana 8A, 31000 Osijek, Croatia

[2]Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia

[3]Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade, Serbia

[4]In Silico Toxicology, Institute of Physiology, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

[5]Institute of Physical Chemistry and Chemical Physics, Department of Chemical Physics, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovakia

关键词: ferulic acid;    5-hydroxyferulic acid;    density functional theory (DFT) and molecular docking;    radical scavenging;    PCET;    radical-radical coupling;   

DOI  :  10.3390/antiox10081303

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown