Triptolide (TP)

the predominant active component of the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF)

has been shown to exert multiple pharmacological effects. However

the clinical applications of TP are limited by its severe adverse effects

especially hepatotoxicity. The aim of this study was to investigate the potential protective effects of Notch1/NF-E2-related factor 2 (Nrf2) signaling on TP-induced hepatotoxicity. In the present study

TP caused oxidative stress and cellular apoptosis in Chang liver cells

which were accompanied by inhibition of the Notch1 activation signal. In addition

the activation of Notch1 by Jagged1 protected against TP-induced cytotoxicity

whereas the inhibition of Notch1 by DAPT or Notch1 siRNA increased the damage. We also found that activation of Notch1 upregulated Nrf2 and heme oxygenase-1 (HO-1) expression and that the inhibition of Notch1 resulted in the opposite effect. Interestingly

a reduction in Nrf2 almost eliminated the protective effect conferred by Jagged1

which indicated that Nrf2 was essential in the protection against TP-induced hepatotoxicity through the activation of Notch1. Overall

these results suggested that Notch1 signaling ameliorated the detrimental effects of TP by decreasing oxidative stress and downregulating apoptosis

and that the Nrf2 signaling pathway was a key downstream mediator of this effect.