Theacrine alleviates inflammation and lung injury in septic mice by mediating SIRT3

Abstract

Purpose: To evaluate the effect of theacrine on sepsis progression and sepsis-induced lung injury and its mechanism of action. Methods: Lung injury model of lipopolysaccharide (LPS)-induced sepsis was made in the mice by injected with 3 mg/kg LPS dissolved in 50 μL PBS or only PBS (control group = 10). The remaining three groups (divided into ten mice per group) were administered theacrine (10, 20, and 40 mg/kg), by oral gavage 1 hour after LPS treatment. Hematoxylin and eosin (H&E) staining was performed to confirm the effect of theacrine on lung injury. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were conducted to determine inflammatory and oxidative stress factors. TUNEL as well as immunoblot assays were carried to confirm its effect on apoptosis and mechanism of action. Results: Theacrine significantly improved lung injury as well as lung relief score in LPS-induced sepsis mice (p < 0.01) and it significantly reversed the increased levels of inflammatory cytokines in a dose-dependent manner in LPS-induced sepsis mice (p < 0.01), In addition, theacrine administration significantly reduced the increased intensity of ROS and MDA levels, and significantly improved the levels of SOD in lung tissues (p < 0.01). Furthermore, it improved LPS-induced apoptosis of lung tissue cells and alleviated lung injury by significantly activating SIRT3 pathway (p < 0.01). Conclusion: Theacrine alleviates inflammation and lung injury in septic mice by mediating SIRT3, thereby making it a potential lead in the development of drugs against sepsis-related inflammation and lung injury.