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Exp Ther Med. 2017 Sep;14(3):2228-2234. doi: 10.3892/etm.2017.4772. Epub 2017 Jul 11.

Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway.

Author information

1
Department of Oncology, Jianhu People's Hospital, Yancheng, Jiangsu 224700, P.R. China.
2
Department of Oncology, Yancheng Third People's Hospital, Yancheng, Jiangsu 224001, P.R. China.
3
Research and Development Department, Solomon Brothers Medical Institute, Wilmington, DE 19803, USA.

Abstract

The aim of the present study was to explore the effect of naringenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model, as well as the underlying mechanism. The animals were randomly assigned to four groups: PBS-treated healthy control (Control), LPS-induced ALI (LPS), vehicle-treated ALI (LPS + Vehicle), and naringenin-treated ALI (LPS + Nar) group. Naringenin (100 mg/kg) was administered orally for 4 consecutive days, starting 3 days prior to induction of ALI. The survival rates of mice, lung wet/dry weight ratios, lung injury score, protein levels of bronchoalveolar lavage fluid (BALF), lactate dehydrogenase (LDH) activity in the BALF, lung myeloperoxidase (MPO) activity, the number of infiltrated neutrophils and reactive oxygen species (ROS) levels (H2O2 and malondialdehyde) were assessed. In addition, the serum and BALF levels of inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and macrophage inflammatory protein 2] were determined, along with the total and the phosphorylated protein levels of phosphatidylinositol 3-hydroxy kinase (PI3K) and AKT in lung tissues. The results showed that naringenin pre-treatment significantly increased the survival rate, improved histopathologic changes, alleviated pulmonary edema and lung vascular leak, downregulated the levels of ROS and reduced neutrophil infiltration as well as the levels of inflammatory cytokines in the serum and BALF. Moreover, naringenin pre-treatment reduced the total and the phosphorylated protein levels of PI3K and AKT. The present study suggested that naringenin pre-treatment ameliorated LPS-induced ALI through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway in mice.

KEYWORDS:

PI3K/Akt pathway; acute lung injury; anti-inflammatory; anti-oxidative; naringenin

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