Triptolide impairs thioredoxin system by suppressing Notch1-mediated PTEN/Akt/Txnip signaling in hepatocytes

Abstract

Triptolide (TP) is the main ingredient of Chinese herb Tripterygium wilfordii Hook f. (TWHF). Despite of its multifunction in pharmaceutics, accumulating evidences showed that TP caused obvious hepatotoxicity in clinic. The current study investigated the role of Notch1 signaling in TP-induced hepatotoxicity. Our data indicated that TP inhibited the protein expression of Notch1 and its active form Notch intracellular domain (NICD) leading to increased PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression. Moreover, PTEN triggered Txnip (thioredoxin-interacting protein) activation by inhibiting Akt phosphorylation, which resulted in reduction of Trx (thioredoxin). In conclusion, TP caused liver injury through initiating oxidative stress in hepatocyte. This study indicated the potency of Notch1 to protect against TP-induced hepatotoxicity.