Naringenin Protects Against Diabetic Nephropathy by Inhibiting Ferroptosis Through SIRT1/FOXO3a Pathway

A study led by Yi Zhou and his team at Xiamen Hospital, affiliated with the Beijing University of Chinese Medicine, has revealed the protective effects of naringenin in diabetic nephropathy (DN). The research highlights naringenin’s ability to regulate ferroptosis, a key driver of renal damage in DN, through the SIRT1/FOXO3a signaling pathway.

Using a high-glucose (HG)-induced cell model of renal tubular epithelial cells (HK-2 cells), the study demonstrated that naringenin improves cell viability, reduces oxidative stress, and enhances mitochondrial function. The treatment lowered levels of ferroptosis markers, including Fe²⁺, oxidized lipid ROS, and ACSL4, while boosting antioxidant defenses such as SOD, GSH-Px, and GPX4.

Importantly, naringenin restored the expression of regulatory proteins like SIRT1, FOXO3a, and Nrf2, which are critical for its anti-ferroptosis effects. Inhibitor experiments further confirmed that SIRT1 plays a central role in mediating these protective actions.

This research provides new insights into the mechanisms behind naringenin’s therapeutic potential in DN, emphasizing its ability to mitigate ferroptosis-related renal damage.

For more details, read the full study.

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