Oligopeptide of RDPEER from watermelon seeds prevents heat stress-induced liver injury by suppressing oxidative stress and inflammation responses

[Display omitted] •Effects of P1 on heat stress-induced liver injury and cell damage were investigated.•P1 improved cell viability and redox homeostasis by suppressing ROS overproduction.•P1 suppressed HPA axis/transaminase hyperactivity and heat shock response.•P1 activated Nrf2/Keap-1 endogenous antioxidant pathway in response to heat stress.•P1 alleviated heat stress caused liver injury by inhibiting inflammatory responses. In this paper, the effect and potential mechanism of supplementary RDPEER (P1, 801 Da), an antioxidant oligopeptide derived from watermelon seeds, on heat stress-induced rat liver injury and HepG2 cell damage were studied. It was observed that supplementation with RDPEER attenuated heat stress-induced hepatocyte injury by increasing HepG2 cell viability, reducing ROS overproduction, improving antioxidant enzyme activity (T-SOD, GSH-Px and CAT) and decreasing MDA content. RDPEER also inhibited HPA axis hyperactivity, serum transaminase activity (AST, ALT) and inflammatory factor levels (INF-γ, IL-6 and TNF-α), activated the endogenous antioxidant pathway (Nrf2/Keap-1), and reduced inflammatory factor transcription (NFκB) and heat shock protein expression (HSP27/72/90). In conclusion, supplementation with RDPEER could enhance antioxidant capacity in vivo and in vitro, reduce the inflammatory and heat shock response to alleviate liver damage caused by heat stress. These findings may provide new insights to alleviate heat stress through nutritional interventions.