On the NRK 52E cells injured by hyperglycemia in vitro and the DKD model in vivo, naringenin treatment markedly reduced the excessive production of intracellular ROS and downregulated the expression of endoplasmic reticulum (ER) stress marker proteins, including p-PERK, eukaryotic initiation factor 2 alpha (eIF2α), X-box-binding protein 1 (XBP1s), ATF4, and CHOP, anti-ER stress to reduce apoptosis of renal cells in diabetes [117]. This evidence concerns the gene ATF4 and Hyperglycemia.