The dermato-protective effects of lucidone from Lindera erythrocarpa through the induction of Nrf2-mediated antioxidant genes in UVA-irradiated human skin keratinocytes

• Lucidone protects human skin keratinocytes from UVA-induced oxidative stress.
• Lucidone decreased UVA-induced DNA damage and apoptosis in HaCaT cells.
• The dermato-protective effect of lucidone is mediated by the induction of antioxidant genes.
• Lucidone-induced transcriptional activation of Nrf2 plays a vital role of this effect.
• Lucidone can be used in sunscreen lotions to prevent UVA-irradiated skin damage.

This study investigated the dermato-protective effects of lucidone, a cyclopentenedione from Lindera erythrocarpa dried fruits, against UVA-induced oxidative stress and apoptosis in human keratinocytes (HaCaT). Pre-treatment with lucidone (1–4 µM) significantly protects keratinocytes from UVA (15 J/cm2)-induced cell death, excessive ROS generation, LDH release, lipid peroxidation, and DNA damage. Notably, lucidone inhibited the UVA-induced apoptosis of HaCaT cells as measured by a reduction of DNA fragmentation, mitochondria dysfunction, and Bcl-2/Bax dysregulation. Furthermore, antioxidant potential of lucidone was directly correlated with the induction of antioxidant genes, including HO-1, NQO-1, and γ-GCLC by transcriptional activation of Nrf2. Treatment with hydrogen peroxide showed cellular byproducts of UVA irradiation-induced cell death, LDH release, and ROS generation, but these phenomena were inhibited by pre-treatment of lucidone. Besides, in Nrf2 knock-down cells, lucidone failed to protect UVA-induced oxidative stress or cell death. Our findings suggest that lucidone is capable of protecting skin cells from UVA-irradiated damage.