
Hesperidin (Hes), a flavonoid compound, was investigated for its therapeutic potential in diabetes mellitus-induced erectile dysfunction (DMED). In vivo experiments on streptozotocin-induced DMED rats and in vitro studies on high glucose (HG)-stimulated HUVECs revealed that Hes activated the Nrf2–HO-1/GPX4 axis, reducing ferroptosis and oxidative stress. Hes partially restored erectile function by increasing Nrf2, GPX4, and HO-1 expression, improving endothelial and smooth muscle cell function, and mitigating cavernous fibrosis. In HG-stimulated HUVECs, Hes attenuated oxidative damage and ferroptosis, effects partially reversed by the Nrf2 inhibitor ML385. These findings highlight the regulatory mechanism of Hes in DMED, suggesting its potential as a preclinical therapeutic agent.
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