Protective Effect of Taxifolin Against Monochloroacetic Acid-Induced Skin Damage via Inhibition of the cGAS/STING/NF-κB Pathway.

Monochloroacetic acid (MCA), a prevalent byproduct of water disinfection, is increasingly detected in aquatic environments, raising concerns about its detrimental effects on skin health. Taxifolin (TAX), a flavonoid with diverse pharmacological properties, has received limited attention in dermatological applications. In this study, TAX significantly alleviated MCA-induced damage in human epidermal keratinocytes (HaCaT cells) was demonstrated. MTT assays revealed that 12.5, 25, and 50 µM concentrations of TAX effectively reversed the MCA-induced decrease in HaCaT cells. Furthermore, immunofluorescence and flow cytometry analyses showed that TAX markedly reduced reactive oxygen species (ROS) levels and apoptosis induced by MCA. In addition, TAX attenuated ROS-mediated DNA damage caused by MCA. Given that DNA damage can activate the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), the involvement of the cGAS-stimulator of interferon genes (STING) pathway was further examined. The results showed that TAX inhibited the activation of cGAS-STING pathway, thereby preventing downstream NF-κB activation and the release of proinflammatory cytokines. These findings demonstrate the protective effect of TAX against MCA-induced skin damage and highlight its potential as a candidate for future dermatological applications.