Zingerone alleviates LPS-induced acute lung injury in mice via Nrf2 pathway / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the effects and mechanisms of zingerone on LPS-induced acute lung injury (ALI) in vivo. Methods:The mice were divided into control group, zingerone group, LPS group, and LPS + zingerone group. Each group was injected intraperitoneally with zingeroneor saline. The mice were injected with LPS after zingerone treatment for 2h and then were sacrificed 4h later. We collected the lung tissue and blood of the mice and determined lung injury by HE staining. Tunnel staining was performed for cell apoptosis. The concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by ELISA assay. And the protein levels of nuclear factor (erythroid-derived2)-like 2 protein (Nrf2) and heme oxygenase-1 (HO-1) were measured by immuno-blot method. And the above-mentioned experiments were repeated by using Nrf2 knockout mice. Results: Compared with those in control group, the lung injury of mice in LPS group aggravated and cell apoptosis rate was increased significantly. Compared with LPS group, the injury was alleviated and apoptosis rate was decreased markedly. Meanwhile, the concentrations of inflammatory cytokines, including IL-6, TNF-α, IL-1β and MDA, were up-regulated notably compared with the control group, the concentration of SOD was decreased; the concentrations of IL-6, TNF-α, IL-1β and MDA in LPS + zingerone group were decreased while SOD was increased compared with LPS group. In addition, LPS inhibited the expressions of Nrf2 and HO-1, zingerone up-regulated the protein levels of Nrf2 and HO-1. After knockdown of Nrf2 gene, the effects of zingerone on lung injury, inflammation and oxidative stress in the mouse model of LPS-induced acute lung injury were weakened. Conclusion: Zingerone alleviates lung injury in mice by inhibiting inflammation and oxidative stress through activating Nrf2 pathway.