Olive Leaf Extract as a Natural By-Product Modulates Oxidative Stress and DNA Damage in Healthy Human Cells

Background: Oxidative stress–induced DNA damage plays a central role in the development of chronic diseases, including cancer, cardiovascular disorders, and age-related pathologies, which collectively impose a substantial burden on public health systems and societal welfare. Preventive health strategies based on sustainable, low-cost, and naturally derived bioactive compounds are therefore of growing interest. Olive leaf extract (OLE), an agricultural by-product rich in polyphenols, represents a promising candidate in this context. Methods: This in vitro study evaluated the concentration-dependent effects of OLE on cell viability, intracellular reactive oxygen species (ROS) generation, and hydrogen peroxide–induced oxidative DNA damage in a healthy human skin fibroblast cell line (CCD-1072Sk). Oxidative DNA damage was assessed by measuring 8-hydroxyguanosine levels. Results: OLE exhibited a dual, concentration-dependent biological effect. At low concentrations (50–300 μg/mL), OLE promoted cell proliferation and significantly reduced intracellular ROS levels, demonstrating antioxidant activity. In contrast, higher concentrations (>400 μg/mL) induced a pro-oxidant response and cytotoxicity, with an IC₅₀ value of 632 μg/mL. Importantly, pretreatment with non-toxic antioxidant concentrations of OLE markedly attenuated hydrogen peroxide–induced oxidative DNA damage, as evidenced by significantly reduced 8-hydroxyguanosine levels. Conclusion: These findings highlight the dual antioxidant and pro-oxidant nature of olive leaf extract and emphasize the importance of dose optimization in preventive health applications. By demonstrating the genoprotective potential of a sustainable agricultural by-product at safe concentrations, this study supports the integration of evidence-based natural compounds into preventive health strategies aimed at reducing chronic disease burden.