Curcumin Attenuates Ferroptosis and Ameliorates Erectile Function in Diabetic Rats by Activating Nrf2/HO-1 Pathway

Previous studies have shown that curcumin has a therapeutic effect on diabetic erectile dysfunction (ED), but the exact mechanism of action remains unclear. In order to ascertain the involvement of ferroptosis in diabetic ED and explore the underlying mechanism by which curcumin mitigates ferroptosis in penile endothelial cells under conditions of high-glucose stimulation, we conducted an investigation utilizing a rat model of diabetes induced by a high-fat diet and streptozotocin injection. The 40 male Sprague-Dawley rats were randomly divided into four groups: blank control, diabetes control, ferroptosis inhibitor treatment, and curcumin treatment. After 8 weeks, the erectile function of all rats was evaluated through electrical stimulation of the cavernous nerve. Histological and molecular changes of the cavernous body were analyzed using western blot and immunohistochemistry. Penile endothelial cells were then treated with appropriate concentrations of high glucose and curcumin to explore the mechanism of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in curcumin's ability to alleviate ferroptosis in endothelial cells stimulated by high glucose. According to research, diabetic rats experience a decrease in erectile function, damaged endothelial cells, and ferroptosis in tissues. However, curcumin treatment has been shown to be effective in improving erectile function and related tissue and molecular changes in diabetic rats. Furthermore, in vitro experiments have confirmed that curcumin can inhibit the occurrence of ferroptosis in penile endothelial cells that are stimulated by high glucose through Nrf2/HO-1 signaling. Curcumin has been found to improve the occurrence of penile ED in diabetic penile endothelial cells. This is achieved by inhibiting the level of ferroptosis, and the mechanism behind this improvement may be linked to the upregulation of the expression level of Nrf2/HO-1.