Kaempferide Inhibits DOX-induced Liver Inflammation by Activating AMPKα/SIRT1

Abstract

Objectives DOX can promote liver cell inflammation and lead to liver cell death. Ka protects and stabilizes liver cells for the treatment of hepatitis, cirrhosis, and other diseases. However, there is no evidence to suggest that Ka is associated with chemotherapy-related liver inflammation. Materials and Methods Treat mice with DOX or Ka to induce or treat liver inflammation. Then, the body weight, liver weight, morphological changes, and liver inflammation of the mice were measured. Western blotting and RT-PCR were used to evaluate the AMPKα/SIRT1/NF-κB inflammatory signaling pathway and inflammatory gene expression. Finally, the above signaling pathways were verified in liver cells. Results DOX causes liver function damage and liver inflammation in mice. The specific manifestations are abnormal liver tissue structure in DOX mice; abnormal elevation of serum liver function markers ALP, ALT, AST, and GGT levels; abnormal elevation of serum inflammatory factors IL-1β, IL-6, IL-10, and TNF-α levels; and increased expression of liver inflammatory genes NF-κB, IL-1β, IL-6, TNF, and VCAM-1. Ka can effectively prevent and treat these changes. However, there was no significant change in the glucose and lipid metabolism levels of each group of mice. Further research suggests that the inhibitory effect of Ka on DOX-induced liver inflammation is mediated by the AMPKα/SIRT1/NF-κB signaling pathway. Primary liver cell studies have also confirmed the involvement of these signaling pathways and proteins. Significance This study demonstrates that Ka can improve DOX-induced liver inflammation, including changes in inflammatory factors or genes in serum and liver tissue. Further research has found that its potential mechanism may be related to the AMPKα/SIRT1/NF-κB signaling pathway.