Title:Hydroxytyrosol Attenuates LPS-Induced Acute Lung Injury in Mice by Regulating Autophagy and Sirtuin Expression
Volume: 17
Issue: 2
Author(s): X. Yang, T. Jing, Y. Li, Y. He, W. Zhang, B. Wang, Y. Xiao, W. Wang, J. Zhang, J. Wei and R. Lin*
Affiliation:
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi,China
Keywords:
Hydroxytyrosol, lipopolysaccharide, autophagy, sirtuin, acute lung injury, respiratory distress syndrome.
Abstract: Background: Recently, the effects of hydroxytyrosol on autophagy during
acute lung injury (ALI) have drawn increasing attention.
Objective: We explored the underlying molecular mechanisms by which hydroxytyrosol
exerts its anti-inflammatory effects in a murine model of ALI by up-regulating autophagy.
Methods: Male BALB/c mice, challenged with intranasal instillations of LPS, were
treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h prior to LPS
exposure. Twenty-four hours later, lung and bronchoalveolar lavage (BAL) fluid samples
were obtained for the determination of lung wet to dry weight (W/D) ratios, protein
leakage levels, and differential counts of inflammatory cells in BAL fluid. LPS-induced
cytokine activity, inflammatory factor levels, sirtuin (SIRT1/3/6) expression, mitogenactivated
protein kinase (MAPK) activation, and autophagy marker expression in ALImice
were examined by western blotting and staining methods. Molecular docking
between HT and SIRT and MAPK was studied with a Sybyl/Surflex module.
Results: LPS-stimulated SIRT inhibition, MAPK phosphorylation, and autophagy
suppression were all notably abolished by HT administration. HT treatment significantly
attenuated pulmonary edema and inflammatory cell infiltration into lung tissues,
accompanied by decreased lung W/D ratios, protein concentrations, and inflammatory
cell levels in BAL fluid. LPS driven release of inflammatory mediators, including TNF-α,
IL-1β, IL-6, IL-10, and MCP-1, was strongly regulated by HT.
Conclusions: The protective effect of HT on lung inflammation in ALI mice may be
attributed to the promotion of autophagy, which is likely associated with the activation of
the SIRT/MAPK signaling pathway. Importantly, this study provides new insight into the
molecular mechanisms of HT and its therapeutic potential in the treatment of acute
respiratory distress syndrome.
