Folic Acid Protects Melanocytes from Oxidative Stress via Activation of Nrf2 and Inhibition of HMGB1

Oxid Med Cell Longev. 2021 Dec 7;2021:1608586. doi: 10.1155/2021/1608586. eCollection 2021.


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.

MeSH terms

  • Antioxidants / pharmacology
  • Apoptosis
  • Folic Acid / pharmacology*
  • Gene Expression Regulation / drug effects*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress*
  • Protective Agents / pharmacology*
  • Vitamin B Complex / pharmacology


  • Antioxidants
  • HMGB1 Protein
  • HMGB1 protein, human
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Protective Agents
  • Vitamin B Complex
  • Folic Acid