Natural Tremella Polysaccharide Mitigates DEHP-Induced Oxidative Stress and Apoptosis via Dual Regulation of Survival and Antioxidant Pathways

Diethylhexyl phthalate (DEHP), a common environmental plasticizer, induces oxidative damage and cell apoptosis without efficient treatment. <i>Tremella fuciformis</i> polysaccharides (TFPs) are known natural antioxidants, yet their protection against DEHP toxicity remains unclear. This study aimed to investigate the protective effects of TFP against DEHP-induced toxicity using both human umbilical vein endothelial cells (HUVECs) and <i>Caenorhabditis elegans</i> models. The results demonstrate that TFPs significantly alleviated DEHP-induced cytotoxicity in HUVECs by reducing reactive oxygen species (ROS) generation and inhibiting mitochondrial apoptosis pathways, which may contribute to the activation of antioxidant systems mediating via Nrf-2. In <i>C. elegans</i>, TFP improved survival rates under DEHP stress and reduced ROS accumulation. This protection was associated with the modulation of the insulin-like pathway and <i>skn-1</i> gene to increase the expressions of antioxidant genes. Our findings reveal that TFP exhibits protection against DEHP-induced oxidative stress and apoptosis through the synergistic regulation of survival and antioxidant pathways, highlighting its potential as a natural dietary intervention for environmental toxicant-induced health risks.