Protective effect of Salidroside on hypoxia-related liver oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways.

High-altitude hypoxia-induced oxidative stress and inflammation played an essential role in the incidence and development of liver injury. Salidroside (Sal), a phenylpropanoid glycoside extracted from the plant Rhodiola rosea, has recently demonstrated antioxidant, anti-inflammatory, and antihypoxia properties. Herein, we hypothesized that salidroside may alleviate hypoxia-induced liver injury via antioxidant and antiinflammatory-related pathways. A high-altitude hypoxia animal model was established using hypobaric chamber. Male SD rats were randomly divided into the control group, hypoxia group, control +Sal group, and hypoxia +Sal group. Salidroside treatment significantly inhibited hypoxia-induced increases of serum and hepatic pro-inflammatory cytokines release, hepatic ROS production and MDA contents; attenuated hypoxia-induced decrease of hepatic SOD, CAT, and GSH-Px activities. Furthermore, salidroside treatment also potentiated the activation of Nrf2-mediated anti-oxidant pathway, as indicated by upregulation of n-Nrf2 and its downstream HO-1 and NQO-1. In vitro study found that blocking the Nrf2 pathway using specific inhibitor ML385 significantly reversed the protective effect of salidroside on hypoxia-induced liver oxidative stress. In addition, salidroside treatment significantly inhibited hepatic pro-inflammatory cytokines release via JAK2/STAT3-mediated pathway. Taken together, our findings suggested that salidroside protected against hypoxia-induced hepatic oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways.