The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress

FEBS Lett. 2008 Jul 23;582(17):2655-62. doi: 10.1016/j.febslet.2008.06.045. Epub 2008 Jun 30.


In this study, we investigated the mechanisms of kahweol protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with kahweol significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Kahweol also up-regulated heme oxygenase-1 (HO-1) expression, which conferred neuroprotection against 6-OHDA-induced oxidative injury. Moreover, kahweol induced PI3K and p38 activation, which are involved in the induction of Nrf2, HO-1 expression, and neuroprotection. These results suggest that regulation of the anti-oxidant enzyme HO-1 via the PI3K and p38/Nrf2 signaling pathways controls the intracellular levels of ROS.

MeSH terms

  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Coffee / chemistry*
  • Cytoprotection*
  • Diterpenes / pharmacology*
  • Dopamine / metabolism
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • NF-E2-Related Factor 2 / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / enzymology
  • Oxidative Stress / drug effects*
  • Oxidopamine / toxicity
  • Phosphatidylinositol 3-Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Coffee
  • Diterpenes
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • kahweol
  • Oxidopamine
  • Heme Oxygenase-1
  • Phosphatidylinositol 3-Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dopamine