Puerarin protects Alzheimer's disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways

Exp Gerontol. 2011 Jan;46(1):30-7. doi: 10.1016/j.exger.2010.09.013. Epub 2010 Oct 13.


Mitochondrial oxidative stress induced by reactive oxygen species (ROS) has been strongly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). We used mitochondrial transgenic neuronal cell cybrid models of sporadic AD (SAD), which overproduce ROS compared to control cybrids, to investigate the protective effects of puerarin, an isoflavone purified from Chinese herb radix of Pueraria lobata, on viability, endogenous ROS and intracellular signaling pathways. SAD cybrids had increased apoptosis and increased accumulation of ROS that was inhibited by puerarin. Western blotting demonstrated that SAD cybrids had increased basal activation of the caspase-3, p38 and c-Jun N-terminal kinase (JNK) that were inhibited by puerarin. Puerarin was also found to decrease Bax/Bcl-2 ratio. These results suggest that expression of SAD mitochondrial genes in cybrids activates oxidative-stress-related signaling pathways and reduces viability, and that the protective effects of puerarin inhibit oxidative-stress-induced apoptosis through down-regulation of Bax/Bcl-2 ratio, which blocks the activation of JNK, p38 and caspase-3. Therefore, puerarin may act as an intracellular ROS scavenger, and protect neurons against oxidative-stress-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Antioxidants / administration & dosage
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Humans
  • Hybrid Cells
  • In Vitro Techniques
  • Isoflavones / pharmacology*
  • Male
  • Microscopy, Electron
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / ultrastructure
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Signal Transduction / drug effects


  • Antioxidants
  • Drugs, Chinese Herbal
  • Isoflavones
  • Neuroprotective Agents
  • CASP3 protein, human
  • Caspase 3
  • puerarin