Background: Cordycepin (CRD) has been identified to alleviate diabetes-induced injuries and complications including diabetic nephropathy (DN). Here, this work focused on probing the specific effects and potential mechanisms of CRD on DN progression.
Methods: High glucose (HG)-induced mouse podocyte cell line (MPC5) was used for in vitro functional analyses. Cell proliferation and apoptosis were determined using cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry, respectively. ELISA analysis detected inflammatory factors. Cell ferroptosis was assessed by measuring the levels of Fe2+, glutathione, reactive oxygen species, and malonaldehyde.
Results: CRD treatment suppressed HG-induced apoptosis, inflammation, and ferroptosis in podocytes. CRD treatment elevated SLC7A11 and GPX4 expression in HG-treated podocytes. The overexpression of SLC7A11 or GPX4 suppressed HG-evoked apoptosis, inflammation, and ferroptosis in podocytes. Moreover, the silencing of SLC7A11 or GPX4 abolished the protective effects of CRD on HG-treated podocytes. Moreover, CRD ameliorated renal structure injury and inflammation in STZ-induced diabetic mice by modulating SLC7A11 or GPX4 expression.
Conclusions: Cordycepin suppressed HG-induced apoptosis, inflammation, and ferroptosis in podocytes in vitro, and ameliorated renal injury and inflammation in STZ-induced diabetic mice by activating the SLC7A11/GPX4 pathway.
Keywords: Cordycepin; Diabetic nephropathy; Ferroptosis.
© 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.