Anti-inflammatory Role of Trilobatin on Lipopolysaccharide-induced Acute Lung Injury through Activation of AMPK/GSK3β-Nrf2 Pathway

Inflammation is essential for the pathological process of acute lung injury (ALI). Trilobatin, a glycosylated dihydrochalcone can show anti-oxidative and anti-inflammation properties. This study aimed to explore whether trilobatin could suppress inflammation in lipopolysaccharide (LPS)-induced ALI. Firstly, mice were injected with trilobatin intraperitoneally, and then LPS was administered intranasally to induce lung injury. Data from analysis of lung edema and pathologic histology of lung tissues indicated that pretreatment with trilobatin alleviated LPS-induced histopathological changes and decreased wet-to-dry weight (W/D) ratio. Moreover, LPS-induced lung injury was attenuated post trilobatin treatment with reduced protein concentration, cell numbers, neutrophils and macrophages in BALF (bronchoalveolar lavage fluid). Secondly, trilobatin treatment decreased the protein level of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) thereby suppressing LPS-induced inflammation. LPS-induced oxidative stress was ameliorated following trilobatin treatment with decreased malondialdehyde (MDA) and increased glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Lastly, trilobatin decreased NF-kappa B phosphorylation and increased Nrf2 through up-regulation of AMPK and GSK3 beta phosphorylation. In conclusion, trilobatin repressed oxidative stress and inflammatory damage by ameliorating LPS-induced ALI through activation of AMPK/GSK3 beta-Nrf2 and inhibition of NF-kappa B.