• Puerarin (PUE) significantly protects HepG2 cells from cadmium-induced apoptosis by reducing oxidative stress and ER stress.
• PUE inhibits the PERK-eIF2α-ATF4-CHOP signaling axis, thereby alleviating ER stress and restoring ER function.
• The protective effect of PUE is dependent on SIRT1 upregulation, which suppresses the PERK pathway and reduces CHOP levels.
• PUE shows promise as a hepatoprotective agent against cadmium-induced liver damage, offering a potential therapeutic strategy.