6-Gingerol activates the Nrf2 signaling pathway to alleviate hydrogen peroxide induced oxidative stress on primary chicken embryo hepatocytes

• H 2 O 2 treatment caused the damage of CEHs, and 6-Gin significantly alleviated CEHs damage. • H 2 O 2 reduced the antioxidant capacity of CEHs and increased inflammatory factors, leading to cell apoptosis. • 6-Gin alleviated the oxidative injury induced by H 2 O 2 , and increased the expression of antioxidant genes and proteins. • 6-Gin alleviates H 2 O 2 -induced CEHs damage by promoting nuclear translocation and activating the Nrf2 signaling pathway. Oxidative stress affects production performance and meat quality of poultry. 6-gingerol (6-Gin) is the main activity component of ginger, has shown promise in alleviating oxidative stress in broilers, However, the specific protection mechanism of 6-Gin against hepatocytes oxidative damage remains unclear. The primary chicken embryo hepatocytes (CEHs) were damaged and the cell viability was decreased by H 2 O 2 , 6-Gin can alleviate the cell injure and oxidative stress. Transcriptomic analysis and further experiments showed that H 2 O 2 significantly suppressed the expression of Nrf2, Keap1, and NQO1, as well as antioxidant enzyme activities, increased inflammatory factors, leading to cell apoptosis. In contrast, 6-Gin effectively reduced these effects by promoting Nrf 2 nuclear translocation and activating the Nrf2 signaling pathway. Furthermore, the protective effects of 6-Gin were eliminated by the Nrf2 inhibitor ML385. In conclusion, 6-Gin exerts antioxidant, anti-inflammatory and anti-apoptotic effects on CEHs through the Nrf2 pathway. This study provides the potential value of 6-Gin for treatment of oxidative stress in broilers.