Liposomes loaded with quercetin for resolution of lung inflammation in a lipopolysaccharide-induced mouse model of sepsis

Abstract

Abstract Quercetin (QU) has been widely used as a dietary supplement and proved useful to treat lung diseases. However, the therapeutic potential of QU may be restricted because of its low bioavailability and poor water solubility. In this study, we investigated the effects of developed QU-loaded liposomes on macrophage-mediated lung inflammation. In vivo , a mouse model of sepsis induced by lipopolysaccharide challenge was used to detect the anti-inflammatory effects of liposomal QU. Hematoxylin/eosin staining and immunostaining were utilized to reveal pathological damage and leukocyte infiltration into the lung tissues. Quantitative reverse transcription-polymerase chain reaction and immunoblotting were used to determine cytokine production in the mouse lungs. In vitro , mouse RAW 264.7 macrophages were treated with free QU and liposomal QU. Cell viability assay and immunostaining were utilized to detect cytotoxicity and distribution of QU in the cells. The in vivo results showed that liposomal encapsulation promoted the inhibitory effects of QU on lung inflammation. Liposomal QU decreased mortality in septic mice with no obvious toxicity on vital organs. Mechanistically, the anti-inflammatory effects of liposomal QU were associated with inhibition of nuclear factor-kappa B-dependent cytokine production and inflammasome activation in macrophages. Collectively, the results showed that QU liposomes mitigated lung inflammation in septic mice through inhibition of macrophage inflammatory signaling.