Protective Effect of Idebenone Against UVB-Induced Photoaging in HaCaT Cells

Ultraviolet B (UVB) irradiation is a key exogenous factor contributing to skin photoaging. Idebenone (IDE), a structural analog of coenzyme Q10 (CoQ10), exhibits potent free radical scavenging capacity and is mainly employed in the treatment of neurodegenerative disorders, and in anti-aging products. However, the molecular mechanisms underlying its photoprotective effects in skin cells remain poorly understood.

This study aims to investigate the protective effects of IDE against UVB-induced photoaging in human immortalized epidermal keratinocytes (HaCaT cells).

We applied IDE to a UVB-induced HaCaT cell photoaging model and found that it significantly ameliorated the photoaging damage caused by UVB irradiation.

Specifically, cell morphology recovered from a shrinkage state toward normal, the positivity rate of senescence-associated β-galactosidase (SA-β-gal) decreased, and enhanced the impaired cell migration and proliferation capacities. Additionally, oxidative stress imbalance was alleviated, as evidenced by a significant reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, along with an increase in superoxide dismutase (SOD) activity. Impaired mitochondrial function was restored, reflected by the repolarization of mitochondrial membrane potential (MMP) and an increase in adenosine triphosphate (ATP) synthesis. Furthermore, the elevated secretion levels of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8) were significantly reduced. Transcriptomic analysis and protein validation revealed that IDE significantly downregulated the expression of IL-3RA and effectively restored the expression of TUBA8.

IDE significantly improved UVB-induced photoaging damage in HaCaT cells through multiple pathways, including restoring cell viability, alleviating oxidative stress damage, reducing pro-inflammatory factor infiltration, and protecting mitochondrial function. Its mechanism of action may involve the regulation of targets such as IL-3RA and TUBA8.