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

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.

Caffeic acid, but not ferulic acid, inhibits macrophage pyroptosis by directly blocking gasdermin D activation

“…As a potent LOX inhibitor, CA was previously reported to prevent H 2 O 2 ‐ and nonsteroidal anti‐inflammatory drug‐induced programmed cell death 54,55 . FA is also described as a LOX inhibitor in previous reports 56,57 . To explore the role of LOX inhibition in pyroptosis and the connection between the anti‐pyroptotic and anti‐LOX activity of CA, we employed another LOX inhibitor, Zileuton 58 .…”

“…54,55 FA is also described as a LOX inhibitor in previous reports. 56,57 To explore the role of LOX inhibition in pyroptosis and the connection between the anti-pyroptotic and anti-LOX activity of CA, we employed another LOX inhibitor, Zileuton. 58 We found that 12.5-50 µM Zileuton failed to suppress the LPS/Nigericininduced release of LDH.…”

Recent Advances in Herbal-Derived Products with Skin Anti-Aging Properties and Cosmetic Applications

“…Ferulic acid is promptly absorbed by the skin when topically applied and protects the skin from UVB radiation-induced skin erythema and pigmentation in cells from human breast reduction surgeries [ 85 ]. Docking studies indicated that ferulic acid and its derivative, 5-hydroxyferulic acid, interact with the active site of the lipoxygenase (LOX) enzyme, with a consequent inhibition of its activity, representing a potential mechanism of skin protection against UV radiation-induced oxidative stress [ 86 ]. Recently, ferulic acid was also evaluated in an elegant split-face comparative study, alone or associated with microneedling [ 25 ].…”

Past and Current Prospectives of Herbal Product for Skin Care

“…Oxidative stress is a key factor in epidermal barrier disruption, skin ageing, and melanogenesis, despite ROS's importance in biological signalling systems. Triggers of oxidative stress in the environment, such as ultraviolet (UV) radiation and visible light, both affect skin parameters in similar ways, resulting in compromised skin barrier function and cosmetically unattractive hyperpigmentation [121,122,123].…”