Oleuropein alleviates sepsis-induced acute lung injury via the AMPK/Nrf-2/HO-1 signaling

Abstract

Objective: To explore the effect of oleuropein on sepsis-induced acute lung injury (ALI) in vitro and in vivo and investigate the underlying mechanism. Methods: In an lipopolysaccharide (LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI, CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis. ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress, respectively. Western blot was applied to determine the expression of apoptosis- and AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) signaling-associated proteins. JC-1 staining, adenosine triphosphate (ATP) assay kit, and MitoSOX Red assays were performed to detect mitochondrial membrane potential, ATP content, and mitochondrial ROS formation, respectively. Moreover, lung injury was evaluated by measuring lung morphological alternations, lung wet-to-dry ratio, myeloperoxidase content, and total protein concentration. Results: Oleuropein reduced inflammatory reaction, oxidative damage, and apoptosis, and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI. Besides, oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway. However, these effects of oleuropein were abrogated by an AMPK inhibitor compound C. Conclusions: Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling, which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

Keywords

• ampk/nrf-2/ho-1 signaling
• inflammatory response
• lung damage
• mitochondrial dysfunction
• oleuropein
• oxidative stress
• sepsis