Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes

Mar Drugs. 2019 Apr 13;17(4):225. doi: 10.3390/md17040225.


Phloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with oxidative stress (hydrogen peroxide, H2O2). The results showed that PG significantly inhibited the H2O2-induced growth inhibition in HaCaT cells, which was associated with increased expression of heme oxygenase-1 (HO-1) by the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PG remarkably reversed H2O2-induced excessive ROS production, DNA damage, and apoptosis. Additionally, H2O2-induced mitochondrial dysfunction was related to a decrease in ATP levels, and in the presence of PG, these changes were significantly impaired. Furthermore, the increases of cytosolic release of cytochrome c and ratio of Bax to Bcl-2, and the activation of caspase-9 and caspase-3 by the H2O2 were markedly abolished under the condition of PG pretreatment. However, the inhibition of HO-1 function using zinc protoporphyrin, a HO-1 inhibitor, markedly attenuated these protective effects of PG against H2O2. Overall, our results suggest that PG is able to protect HaCaT keratinocytes against oxidative stress-induced DNA damage and apoptosis through activating the Nrf2/HO-1 signaling pathway.

Keywords: Nrf2/HO-1; ROS; keratinocytes; oxidative stress; phloroglucinol.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line
  • Cytochromes c / metabolism
  • DNA Damage / drug effects*
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Phloroglucinol / pharmacology*
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects


  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • Cytochromes c
  • Hydrogen Peroxide
  • Phloroglucinol
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Caspase 3