Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy

Neurochem Int. 2013 Jul;63(1):1-9. doi: 10.1016/j.neuint.2013.04.005. Epub 2013 Apr 23.


Celastrol, an active component found in the Chinese herb tripterygium wilfordii has been identified as a neuroprotective agent for neurodegenerative diseases including Parkinson's disease (PD) through unknown mechanism. Celastrol can induce autophagy, which plays a neuroprotective role in PD. We tested the protective effect of celastrol on rotenone-induced injury and investigated the underlying mechanism using human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were treated with celastrol before rotenone exposure. The cells survival, apoptosis, accumulation of α-synuclein, oxidative stress and mitochondrial function, and autophagy production were analyzed. We found celastrol (500 nM) pre-treatment enhanced cell viability (by 28.99%, P<0.001), decreased cell apoptosis (by 54.38%, P<0.001), increased SOD and GSH (by 120.53% and 90.46%, P<0.01), reduced accumulation of α-synuclein (by 35.93%, P<0.001) and ROS generation (by 33.99%, P<0.001), preserved MMP (33.93±3.62%, vs. 15.10±0.71% of JC-1 monomer, P<0.001) and reduced the level of cytochrome C in cytosol (by 45.57%, P<0.001) in rotenone treated SH-SY5Y cells. Moreover, celastrol increased LC3-II/LC3 I ratio by 60.92% (P<0.001), indicating that celastrol activated autophagic pathways. Inhibiting autophagy by 3-methyladenine (3-MA) abolished the protective effects of celastrol. Our results suggested that celastrol protects SH-SY5Y cells from rotenone induced injuries and autophagic pathway is involved in celastrol neuroprotective effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Humans
  • Neuroblastoma / immunology
  • Neuroblastoma / pathology*
  • Pentacyclic Triterpenes
  • Rotenone / pharmacology*
  • Triterpenes / pharmacology*


  • Pentacyclic Triterpenes
  • Triterpenes
  • Rotenone
  • celastrol