Cudratricusxanthone A attenuates sepsis-induced liver injury via SIRT1 signaling

Abstract

Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudraniatricuspidata Bureau, is known to possess antithrombotic, antiproliferative, and antiinflammatory activities. It remains unclear that CTXA can improve hepatoprotective activity in vivo. The objective of this study was to investigate the effect of CTXA on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p.) in mice, and 12 hr later, they were treated intravenously with CTXA. Administration of LPS significantly increased mortality, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and serum inflammatory cytokines. CTXA treatment effectively countered these effects of LPS. Further, LPS treatment markedly increased the expression of myeloperoxidase, phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), and expressions of nuclear proteins, such as nuclear factor (NF)-κB and phosphorylated c-Jun. Additionally, LPS increased the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. All these effects of LPS were attenuated by CTXA. Moreover, CTXA increased the expression of sirtuin-1 (SIRT1) and reduced the expression of acetylated forkhead box O1 box O1 (Ac-FoxO1), acetylated Ac-p53, and acetylated nuclear factor-kappa beta (Ac-NF-κB). In conclusion, CTXA alleviates LPS-induced liver injury by reducing inflammatory responses and the potential mechanism is associated with SIRT1 signaling activation and finally could be used to treat liver diseases.