Cinnamon-Derived Compounds Reduce PD-L1 Expression in UV-Exposed Human Skin Cell Line

Background/Objective: Ultraviolet A and B (UVAB) radiation is a major environmental factor that induces DNA damage and upregulates programmed death-ligand 1 (PD-L1) expression in skin cells, thereby contributing to immune evasion and impaired tissue repair. This study evaluated the protective effects of two purified compounds, Cinnamtannin B1 (CTB-1) and Cinnamtannin D1 (CTD-1), as well as cinnamon extract, in UVAB-irradiated human keratinocyte HaCaT cells. Methods: HaCaT cells were exposed to low (20 kJ/m2 UVA, 1.3 kJ/m2 UVB), medium (30 kJ/m2 UVA, 2 kJ/m2 UVB), and high (40 kJ/m2 UVA, 2.7 kJ/m2 UVB) UVAB doses of UVAB radiation. Dose-dependent effects of CTB-1 and CTD-1 (0, 5, 10, 25, and 50 µg/ mL) and cinnamon extract (0, 5, 10, 50, and 100 µg/mL), as well as time-dependent effects (12, 24, and 72 h), were evaluated by measuring PD-L1 expression, cell viability, and DNA damage. Results: CTD-1 was the most effective compound, significantly reducing UVAB-induced PD-L1 expression and DNA double-strand breaks without compromising cell viability. CTB-1 also demonstrated protective effects at specific doses and time points; however, higher concentrations reduced cell viability. Cinnamon extract was protective at low concentrations but cytotoxic at higher doses. Conclusions: CTD-1, CTB-1, and cinnamon extract attenuated UVAB-induced cellular damage in HaCaT cells, with CTD-1 demonstrating the most favorable protective profile. These findings support the potential of cinnamon-derived compounds as therapeutic candidates for preventing UVAB-induced skin damage and immune dysregulation.