Puerarin protects against acetaminophen‐induced oxidative damage in liver through activation of the Keap1/Nrf2 signaling pathway

Puerarin (Pue) is a kind of isoflavone compound extracted from Pueraria lobata, which has significant antioxidant activity. Excessive use of acetaminophen (APAP) can cause oxidative stress in the liver and eventually lead to acute liver injury. The purpose of this study was to investigate the protective effect and the mechanism of puerarin on APAP‐induced liver oxidative damage. In in vitro experiments, puerarin significantly increased the cell activity of HepG2 cells, reduced the ROS accumulation, alleviated the oxidative damage and mitochondrial dysfunction. In in vivo studies, our results showed that puerarin enhanced antioxidant activity and alleviated histopathological damage. Further studies showed that puerarin decreased the expression of Keap1, promoted the nuclear migration of Nrf2, and up‐regulated the expression of GCLC, GCLM, HO‐1 and NQO1. This study demonstrated that puerarin can protect APAP‐induced liver injury via alleviating oxidative stress and mitochondrial dysfunction by affecting the nuclear migration of Nrf2 via inhibiting Keap1.