Anemonin inhibits sepsis-induced acute kidney injury via mitigating inflammation and oxidative stress.

Abstract

Elevated inflammation and oxidative stress (OS) are the main pathologic features of acute kidney injury (AKI)-caused by sepsis. Here, we made an investigation into the protective effects of the natural compound Anemonin (ANE) on sepsis-induced AKI both in vitro and in vivo. Lipopolysaccharide (LPS) was applied to construct an in vitro AKI model in renal tubular epithelial cells, and the septic C57BL/6J mouse model was constructed via cecal ligation and puncture (CLP). Cell viability and apoptosis were detected. The levels of p53, Bax, Bcl2, Caspase3, Caspase8, Caspase9, AMP-activated protein kinase (AMPK), Sirt-1, and forkhead box O3 were determined by Western Blot or RT-PCR. The reactive oxygen species level and OS markers were measured. Furthermore, the pathological changes of kidneys were evaluated by hematoxylin-eosin staining and immunohistochemistry. As per the information presented, ANE improved LPS-elicited apoptosis, inflammatory response, and OS in a dose-dependent pattern in renal tubular epithelial cells. Besides, ANE activated the AMPK/Sirt-1 pathway, and the AMPK inhibitor (Compound C) and Sirt-1 inhibitor (EX-527) significantly attenuated ANE-mediated protection on renal tubular epithelial cells. In vivo, ANE mitigated the levels of serum creatinine and urea nitrogen in the CLP-induced mouse sepsis model, reduced the renal tissue injury score, and attenuated OS, inflammation, and apoptosis levels in the kidney. Taken together, this study suggested that ANE has protective effects in sepsis-triggered AKI through repressing inflammation, OS, and cell apoptosis by activating the AMPK/Sirt-1 pathway.