Abstract
Vitiligo is a cutaneous depigmentation disease due to loss of epidermal melanocytes. Accumulating evidence has indicated that oxidative stress plays a vital role in vitiligo via directly destructing melanocytes and triggering inflammatory response that ultimately undermines melanocytes. Folic acid (FA), an oxidized form of folate with high bioavailability, exhibits potent antioxidant properties and shows therapeutic potential in multiple oxidative stress-related diseases. However, whether FA safeguards melanocytes from oxidative damages remains unknown. In this study, we first found that FA relieved melanocytes from H2O2-induced abnormal growth and apoptosis. Furthermore, FA enhanced the activity of antioxidative enzymes and remarkably reduced intracellular ROS levels in melanocytes. Subsequently, FA effectively activated nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown blocked the protective effects of FA on H2O2-treated melanocytes. Additionally, FA inhibited the production of proinflammatory HMGB1 in melanocytes under oxidative stress. Taken together, our findings support the protective effects of FA on human melanocytes against oxidative injury via the activation of Nrf2 and the inhibition of HMGB1, thus indicating FA as a potential therapeutic agent for the treatment of vitiligo.
Highlights
Vitiligo is an acquired depigmentation dermatosis with an estimated prevalence of 1% worldwide [1]
reactive oxygen species (ROS) facilitates the release of high-mobility group protein B1 (HMGB1) that belongs to damage-associated molecular patterns (DAMPs) with strong proinflammatory effects from melanocytes [7,8,9,10]
HMGB1 subsequently causes the production of chemokines in adjacent keratinocytes and the maturation of dendritic cells (DCs) in a paracrine way, which promotes the formation of cytotoxic T cells (CTLs) that undermine melanocytes in vitiligo [7]
Summary
Vitiligo is an acquired depigmentation dermatosis with an estimated prevalence of 1% worldwide [1]. Along with the deficiency of antioxidant system of melanocytes, especially nuclear factor E2related factor 2 (Nrf2) pathway that is a master regulator of antioxidative response [4, 5], reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) is excessively accumulated in vitiligo [6]. Melanocytes are susceptible to ROS-induced apoptosis in vitiligo [3, 5]. ROS facilitates the release of high-mobility group protein B1 (HMGB1) that belongs to damage-associated molecular patterns (DAMPs) with strong proinflammatory effects from melanocytes [7,8,9,10]. Oxidative stress plays a vital role in vitiligo via direct oxidative damages on melanocytes and triggering cutaneous T cell response that targets melanocytes
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