Protective effects of Astragaloside IV against UVA-induced oxidative stress and apoptosis in HaCaT keratinocytes: an integrated in silico and in vitro study

OBJECTIVES: Ultraviolet A (UVA) radiation induces oxidative stress and apoptosis in keratinocytes, contributing to skin photodamage. Astragaloside IV (ASIV) has antioxidant and cytoprotective activities. This study investigated whether ASIV protects human keratinocytes against UVA-induced oxidative injury and explored potential associated signaling pathways. METHODS: UVA. Cell viability, proliferation, migration, apoptosis, and cell cycle progression were evaluated by CCK-8, colony formation, scratch wound healing, and flow cytometry. SOD, GSH, MDA, ROS, and mitochondrial membrane potential (MMP) were measured to assess oxidative stress and mitochondrial function. PI3K/AKT and apoptosis-related proteins were detected by western blotting. RESULTS: UVA irradiation increased p-PI3K/PI3K, p-AKT/AKT, and cleaved caspase-3/caspase-3 ratios and decreased the BCL-2/BAX ratio. ASIV pretreatment reduced p-PI3K/PI3K and p-AKT/AKT ratios, decreased caspase-3 cleavage, and increased the BCL-2/BAX ratio compared with the UVA group. These changes were accompanied by improved antioxidant status, preserved MMP, and reduced apoptosis. CONCLUSIONS: ASIV pretreatment attenuated UVA-induced injury in HaCaT keratinocytes, reflected by improved antioxidant status, preserved MMP, and reduced apoptosis. These effects were accompanied by altered PI3K/AKT phosphorylation, although causal regulation of PI3K/AKT signaling was not established. ASIV may warrant further investigation as a protective compound against skin photodamage.