Triptolide inhibits amyloid-β production and protects neural cells by inhibiting CXCR2 activity

J Alzheimers Dis. 2013;33(1):217-29. doi: 10.3233/JAD-2012-120841.

Abstract

Triptolide, a biologically active natural product from Tripterygium wilfordii, protects neurons from inflammation-mediated damage. Our results showed for the first time that triptolide inhibited the expression of CXCR2 and presenilin in a neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid-β1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore, our study indicates that the neural protective effect of triptolide is largely mediated by inhibiting CXCR2 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / biosynthesis
  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Epoxy Compounds / pharmacology
  • HEK293 Cells
  • Humans
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / biosynthesis
  • Phenanthrenes / pharmacology*
  • Rats
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Receptors, Interleukin-8B / metabolism
  • Tripterygium*

Substances

  • Amyloid beta-Peptides
  • Diterpenes
  • Epoxy Compounds
  • Neuroprotective Agents
  • Peptide Fragments
  • Phenanthrenes
  • Receptors, Interleukin-8B
  • amyloid beta-protein (1-42)
  • triptolide