Vitexin protects melanocytes from oxidative stress via activating MAPK-Nrf2/ARE pathway

Vitiligo is the most common type of depigmented skin disease. Cellular oxidative stress caused by reactive oxygen species (ROS) has been implicated in the pathogenesis of vitiligo. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays an important role in melanocytes against hydrogen peroxide (H₂O₂) induced oxidative stress. In addition, vitexin may protect vitiligo by inhibiting oxidative stress and inflammation.

In the present study, we aimed to investigate the antioxidant effect of vitexin-activated mitogen-activated protein kinase (MAPK)-Nrf2/ARE axis in vitiligo.

MTT assay identified cell viability of human melanocyte PIG1. Cell apoptosis was evaluated by flow cytometry. Gene and protein expression levels were analyzed by quantitative real-time PCR (qPCR) and Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory factors and ROS production.

Vitexin inhibited H₂O₂-induced melanocyte apoptosis and promoted cell proliferation. Moreover, vitexin decreased expression of interleukin-1β (IL-1β), IL-17A, and ROS in melanocytes induced by H₂O₂. Subsequently, activation of MAPK-Nrf2/ARE signaling was readily induced by vitexin treatment, as evidenced by the upregulation of antioxidant genes including heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Knockdown of Nrf2 reversed the protective effect of vitexin on H₂O₂-induced melanocytes. And, knockdown of Nrf2 increased the expression of IL-1β, IL-17A and ROS, and reduced HO-1 and SOD expression.

Vitexin protected melanocytes from oxidative stress by activating MAPK-Nrf2/ARE signaling pathway. Our results suggested that the role of the Nrf2/ARE axis in the antioxidant defense of melanocytes, and the potential therapeutic strategy for vitiligo.