Therapeutic potential of hesperidin in diabetes mellitus‐induced erectile dysfunction through Nrf2‐mediated ferroptosis and oxidative stress

• DOI: 10.1111/andr.13814
• Publication Date: 2024-11-26T07:39:11Z
• Authors: Sheng Xin; Wen Song; Jiaquan Mao; Peng Hu; Zhong Chen; Jihong Liu; Xiaodong Song; Qian Fang; Kai Cui
• Keywords: Streptozocin

Abstract Background Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus‐induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked induction of both ferroptosis oxidative stress, which are mediated nuclear factor E2 related 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, revealed activate Nrf2 certain diabetic complications, yet efficacy Hes on DMED specific mechanism remain unclear. Objectives To elucidate potential regulating Nrf2‐mediated stress DMED. Materials methods rats were constructed through intraperitoneal injection streptozotocin (STZ), partially supplemented Hes. In parallel, vitro research utilized human umbilical vein endothelial cells (HUVECs), glucose addition simulating high (HG) environment, induced or ML385 (an inhibitor). Penile tissues HUVECs harvested for subsequent analyses. Results The results this study indicate that reversed impaired function. expression Nrf2, glutathione peroxidase 4 (GPX4), heme oxygenase‐1 (HO‐1) elevated after supplementing Hes, resulted an inhibition stress. Moreover, quantity function effector restored, cavernous fibrosis was ameliorated. HG‐induced HUVECs, ameliorated effects reversed. Conclusions exerts therapeutic effect regulatory Nrf2–HO‐1/GPX4 axis, concurrently revitalizing smooth muscle cells, diminishing fibrosis. Our provides robust preclinical evidence employing treating