Curcumin activates defensive genes and protects neurons against oxidative stress

Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):395-403. doi: 10.1089/ars.2006.8.395.

Abstract

Spices and herbs often contain active phenolic substances endowed with potent antioxidative properties. We had previously shown that curcumin, the yellow pigment in curry, strongly induced HO-1 expression and activity in rat astrocytes. In the CNS, HO-1 has been reported to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. Treatment of astrocytes with curcumin upregulated expression of HO-1 protein at both cytoplasmic and nuclear levels, as shown by immunofluorescence analysis under laser-scanning confocal microscopy. A significant expression of quinone reductase and glutathione S transferase, two members of phase II detoxification enzymes, was found in astrocytes exposed to 5-15 microM curcumin. Moreover, the effects of curcumin on HO-1 activity were explored in cultured hippocampal neurons. Elevated expression of HO-1 mRNA and protein were detected after 6 h incubation with 5-25 microM curcumin. Higher concentrations of curcumin (50-100 microM) caused a substantial cytotoxic effect with no change in HO-1 protein expression. Interestingly, pre-incubation (18 h) with curcumin resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of heme oxygenase activity. This study gives additional support to the possible use of curcumin as a dietary preventive agent against oxidative stress-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Cell Nucleus / metabolism
  • Curcumin / pharmacology*
  • Cytoplasm / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic*
  • Glucose Oxidase / metabolism
  • Heme Oxygenase-1 / metabolism
  • Hippocampus / pathology
  • Microscopy, Confocal
  • Neurons / metabolism
  • Neurons / pathology*
  • Oxidative Stress*
  • Rats

Substances

  • Enzyme Inhibitors
  • Glucose Oxidase
  • Heme Oxygenase-1
  • Curcumin