Protective Effects of Violaxanthin on Cellular Oxidative Stress via NRF2 Activation in H2O2-Stimulated Human Keratinocytes

Excessive accumulation of reactive oxygen species from exogenous and endogenous stressors can cause cellular damage. Chlorella contains diverse bioactive compounds, and violaxanthin, a major carotenoid pigment found in Chlorella sp. HS-V, has been reported to possess anti-inflammatory, anticancer, and antioxidant properties. We investigated the effect of violaxanthin on hydrogen peroxide (H2O2)-induced oxidative stress in human keratinocytes. Chlorella sp. HS-V extract significantly restored the H2O2-induced decrease in cell viability. Similarly, violaxanthin reduced H2O2-induced cytotoxicity and intracellular reactive oxygen species levels, which was associated with the upregulation of antioxidant enzyme expression. Under H2O2-induced oxidative stress conditions, violaxanthin may enhance cellular antioxidant defense by promoting nuclear factor erythroid 2-related factor 2 (NRF2) translocation through the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) signaling pathway. Additionally, violaxanthin improved H2O2-impaired wound healing in HaCaT human keratinocyte cells and reduced senescence-associated beta-galactosidase-positive normal human epidermal keratinocytes. Overall, these findings suggest that violaxanthin may serve as a potential therapeutic agent for mitigating oxidative stress-induced cellular dysfunction.