Caffeic Acid Protects Keratinocytes from PM_2.5 by Regulating ROS, Mitochondrial Integrity, and JNK Activation

Caffeic acid (CA) is a naturally occurring phenolic compound known for its strong antioxidant and cytoprotective properties. Particulate matter (PM) with an aerodynamic diameter of 2.5 µm (PM_2.5) or less is a major atmospheric pollutant that induces excessive oxidative stress and apoptosis in human skin cells, contributing to various adverse effects on the skin. In this study, we investigated the protective role of CA against PM_2.5-induced cellular injury in human HaCaT keratinocytes. CA reduced PM_2.5-induced reactive oxygen species (ROS) accumulation and mitigated oxidative damage, including lipid peroxidation, protein carbonyl formation, mitochondrial membrane depolarization, and intracellular calcium overload. In addition, CA attenuated PM_2.5-induced apoptosis by upregulating B-cell lymphoma 2 (Bcl-2) and suppressing Bcl-2-associated X protein (Bax), caspase-3, caspase-9, and phosphorylated c-Jun N-terminal kinase (phospho-JNK). Collectively, these findings demonstrate that CA protects HaCaT keratinocytes from PM_2.5-induced oxidative stress and apoptosis by regulating the Bcl-2/Bax axis and inhibiting JNK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for preventing pollutant-induced skin damage.