Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway

Cell Stress Chaperones. 2020 Mar;25(2):277-285. doi: 10.1007/s12192-020-01071-7. Epub 2020 Jan 18.


Vitiligo is a chronic, autoimmune destruction of melanocytes, resulting in progressively expanding depigmented skin patches. Severity of the disorder, which affects approximately 1% of humans, may be mitigated using topical corticosteroids combined with phototherapy; along with other clinical strategies; however, no definitive cures are currently available. Here, the capacity of apigenin, a plant-derived aglycone, to inhibit oxidative stress-mediated melanocyte depletion in vitro using a PIG3V vitiligo perilesional melanocyte cell model is evaluated. PIG3V cells, treated with selected doses of apigenin, were challenged with H2O2, then assessed for viability and the oxidative stress-related parameters: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) by enzyme-linked immunoabsorbent assay (ELISA). Additionally, expression of nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) and downstream targets was detected using Western blotting. Outcomes demonstrated that compared with negative control cultures, apigenin-treated cells exhibited enhanced viability. Likewise, apigenin enhanced expression of the cellular anti-oxidants SOD, CAT, and GSH-Px, but inhibited production of MDA, an oxidative stress biomarker. Interestingly, the expression and nuclear localization of the Nrf2 transcription factor, an important regulator oxidative stress and its downstream target genes, was significantly increased by apigenin treatment. Apigenin influence on Nrf2 was further validated by experiments demonstrating that Nrf2 knockdown cells failed to exhibit significant apigenin-mediated effects on cell viability and oxidative stress. Apigenin's non-toxicity and ability to affect multiple oxidative stress-related parameters through its effects on Nrf2 signaling in melanocytes suggests that it may prove to be a valuable therapeutic tool in long-term management of vitiligo.

Keywords: Apigenin; Melanocyte; Nuclear factor erythroid 2p45 (NF-E2)–related factor 2 (Nrf2); Oxidative stress; Vitiligo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apigenin / pharmacology*
  • Catalase / metabolism
  • Cell Line
  • Cell Survival / drug effects*
  • Glutathione Peroxidase / metabolism
  • Humans
  • Melanocytes* / drug effects
  • Melanocytes* / pathology
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology
  • Superoxide Dismutase / metabolism
  • Vitiligo / drug therapy*


  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Protective Agents
  • Apigenin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase