Abstract

This study investigated the protective effects and underlying mechanisms of ellagic acid (EA) against high-fat diet (HFD)-induced obesity. Using network pharmacology, STAT3 and AKT1 were identified as pivotal regulatory targets. In vivo experiments demonstrated that EA intervention significantly reduced body weight inducement, improved lipid profiles, and attenuated intestinal oxidative stress and inflammation in HFD-fed rats. Furthermore, EA restored intestinal architecture and mitochondrial morphology. Mechanistically, EA markedly downregulated the expression of PPARG, STAT3 and p-AKT1 in both intestinal tissues and TNF-α-stimulated HaCaT cells. Collectively, these findings suggest that EA prevents HFD-induced obesity by alleviating intestinal oxidative stress and mitochondrial dysfunction through the modulation of the PPARG/STAT3/p-AKT1 signaling axis. This study provides novel evidence for EA as a potential natural bioactive compound for the management of metabolic disorders.