Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: relevance for anti-aging intervention

Mol Nutr Food Res. 2011 Mar;55(3):430-42. doi: 10.1002/mnfr.201000221. Epub 2010 Oct 11.


Scope: Curcumin, a component of the spice turmeric, was tested for its potential hormetic anti-aging effects as an inducer of mild stress.

Methods and results: Early passage young human skin fibroblasts treated with low doses of curcumin (below 20 μM) showed a time- and concentration-dependent induction of heme oxygenase-1 (HO-1), followed by compensatory increase in glutathione-S-transferase activity, GSH levels and GSH/GSSG ratio. These effects were preceded by induction of oxidative stress (increased levels of reactive oxygen species and DNA damage) and impairment of cells' GSH redox state. Curcumin also induced nuclear factor-erythroid-2-related factor 2 accumulation in the nuclei. The use of the antioxidant N-acetyl cysteine prevented the induction of HO-1 by curcumin. Pharmacological inhibition of phosphatidylinositol 3-kinase, but not other kinases, significantly prevented curcumin-induced HO-1 levels, which was corroborated by the induction of phospho-Akt levels by curcumin. Late passage senescent cells already had higher HO-1 levels, and further induction of HO-1 by curcumin was considerably impaired. The induction of stress responses by curcumin in human cells led to protective hormetic effects to further oxidant challenge.

Conclusion: Curcumin induces cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3-kinase/Akt pathway and redox signaling, supporting the view that curcumin-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Adult
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Cellular Senescence*
  • Curcuma / chemistry
  • Curcumin / pharmacology*
  • DNA Damage
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Glutathione Disulfide / analysis
  • Glutathione Transferase / analysis
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts / chemistry
  • Reactive Oxygen Species / analysis
  • Signal Transduction
  • Skin / metabolism
  • Spices


  • Antioxidants
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • Reactive Oxygen Species
  • turmeric extract
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Glutathione Transferase
  • Curcumin
  • Glutathione Disulfide
  • Acetylcysteine