Through modulating SIRT3, theacrine reduces inflammation and lung damage in septic mice.

Abstract

The goal of this study is to determine how theacrine affects the development of sepsis and the severity of lung
damage caused by sepsis. Methods: The mice were given injections of 3 mg/kg LPS dissolved in 50 μL PBS or only
PBS (control group = 10), creating a lung damage model of lipopolysaccharide (LPS)-induced sepsis. One hour
after LPS treatment, theacrine was orally gavaged to the other three groups of mice (ten mice per group) at doses
of 10, 20, and 40 mg/kg, respectively. The impact of theacrine on lung damage was confirmed by hematoxylin and
eosin (H&E) staining. We measured oxidative stress and inflammatory factors using enzyme-linked
immunosorbent assays (ELISA) and quantitative polymerase chain reactions (qPCR). The impact on apoptosis and
mechanism of action were confirmed using TUNEL and immunoblot tests. Results: In mice with LPS-induced
sepsis, theacrine had a significant impact on lung injury and lung relief score (p < 0.01). It also reversed the
increased levels of inflammatory cytokines in a dose-dependent manner (p < 0.01). Furthermore, theacrine
significantly reduced the intensity of increased levels of ROS and MDA, and improved the levels of SOD in lung
tissues (p < 0.01). In addition, it reduced lung damage and enhanced LPS-induced cell death in the lungs via
activating the SIRT3 pathway (p < 0.01). Results: Theacrine reduces inflammation and lung damage in septic mice
by modulating SIRT3, suggesting it may be a promising therapeutic development lead for sepsis-related lung injury
and inflammation. Tags: SIRT3 pathway, oxidative stress, sepsis, lung damage, theacrine