The study investigates the mechanism by which curcumin and caffeic acid phenethyl ester (CAPE) induce the expression of heme oxygenase-1 (HO-1) in renal epithelial cells. Curcumin and CAPE were found to stimulate the transcription factor Nrf2 and activate the antioxidant-responsive element (ARE) in a concentration- and time-dependent manner. This activation of Nrf2 led to increased HO-1 protein expression and activity. The study also demonstrated that curcumin and CAPE promote the inactivation of the Nrf2-Keap1 complex, enhancing Nrf2 binding to the AREs in the HO-1 promoter. Additionally, the p38 mitogen-activated protein kinase (MAPK) pathway was identified as crucial for curcumin-mediated HO-1 induction. These findings highlight the importance of the Nrf2/ARE pathway in the HO-1 induction by curcumin and CAPE, suggesting potential therapeutic applications in conditions involving oxidative stress and cellular damage.The study investigates the mechanism by which curcumin and caffeic acid phenethyl ester (CAPE) induce the expression of heme oxygenase-1 (HO-1) in renal epithelial cells. Curcumin and CAPE were found to stimulate the transcription factor Nrf2 and activate the antioxidant-responsive element (ARE) in a concentration- and time-dependent manner. This activation of Nrf2 led to increased HO-1 protein expression and activity. The study also demonstrated that curcumin and CAPE promote the inactivation of the Nrf2-Keap1 complex, enhancing Nrf2 binding to the AREs in the HO-1 promoter. Additionally, the p38 mitogen-activated protein kinase (MAPK) pathway was identified as crucial for curcumin-mediated HO-1 induction. These findings highlight the importance of the Nrf2/ARE pathway in the HO-1 induction by curcumin and CAPE, suggesting potential therapeutic applications in conditions involving oxidative stress and cellular damage.