Effects of Daphnetin on Experimental Acute Pancreatitis-Associated Acute Lung Injury in Mice

Abstract

Background and Aim. Daphnetin, an active monomer ingredient extracted from D. marginata, is proved to have anti-inflammatory and antioxidant effect. The aim of this study is to explore the effect and possible mechanism of daphnetin on acute lung injury (ALI) associated with acute pancreatitis (AP) in mice. Methods. A total of 36 mice were randomly assigned into three groups: control group, AP group, and daphnetin group. The mouse model of AP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 6 and 12 h after daphnetin treatment, respectively. The pathological changes of lung and pancreas were determined by hematoxylin-eosin staining and the pathological scores. Levels of IL-1β, IL-6, and TNF-α in serum and lung and the activity of myeloperoxidase (MPO) in lung tissue homogenate were detected by ELISA. The protein level of toll-like receptor 4 (TLR4), phospho-nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor-kappa B p65 (NF-κB p65), and hypoxia-inducible factor 1 alpha (HIF-1α) in the lung was detected by Western blot. Results. Results showed extensive neutrophil infiltration, hemorrhage, and edema in the pancreas tissues or lung tissues in mice with AP. The daphnetin treatment improved pathological changes in the lung tissues of AP mice. The MPO activity and the levels of inflammatory cytokines including IL-1β, TNF-α, and IL-6 of lung tissues and serum in the AP group were significantly higher than those in the control group ( P < 0.05), and daphnetin intervention significantly reversed the changes ( P < 0.05). Compared with the control mice, the protein levels of TLR4, p-NF-κB p65, and HIF-1α were significantly higher in the lung tissue of the AP mice ( P < 0.05), while daphnetin treatment decreased these protein expression levels. No significant difference was observed in the NF-κB p65 level among control, AP, and daphnetin groups ( P > 0.05). Conclusions. Daphnetin exerted a protective effect on the acute lung injury induced by SAP in mice. The mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α pathway to reduce the release of inflammatory factors.