Hyperoside alleviated N-acetyl-para-amino-phenol-induced acute hepatic injury via Nrf2 activation

N-acetyl-para-amino-phenol (APAP) acute hepatic injury is receiving increasing attention. In the present study, we examined the effects of Hyperoside (Hype) on APAP-induced acute hepatic injury. Oral administration of Hype dose-dependently attenuated the index of hepatic injury, including the production of AST, ALT, and ALP. Increased glutathione (GSH) and decreased ROS production induced by Hype demonstrated its potential antioxidant capacity. In addition, Nrf2 and its downstream genes were markedly activated by Hype. Furthermore, enhanced levels of SOD, GST, and GSH-Px were markedly suppressed by Hype in a dose-dependent manner. At the same time, decreased LPO was also detected in Hype-treated mice. The in vitro study verified a protective effect of Hype on APAP-induced injuries in LO2 cells. Moreover, the regulatory effect was found to be mostly dependent on Nrf2 which decreased LDH and ALT generation and increased cell viability. Nrf2-silenced LOS cells were sensitive to APAP-induced injury, while Hype did not exhibit any further effects on LO2 cells, which demonstrate the critical role of Nrf2 in this process. Taken together, our results demonstrated the ability of Hype to inhibit APAP-induced acute hepatic injury and its potential use in the treatment of Nrf2-associated diseases.