Naringenin inhibits high glucose‑induced ROS‑dependent neuronal apoptosis via the STAT3 signalling pathway

Diabetic cognitive impairment (DCI) is a common neurological complication of diabetes for which effective treatments remain lacking. Naringenin possesses antioxidant, anti‑inflammatory, and neuroprotective properties, but its mechanism of action in DCI remains unclear. This study aimed to investigate whether naringenin protects against high glucose‑induced neuronal injury via the STAT3 signalling pathway.

SH‑SY5Y cells were treated with 50 mM glucose for 48 h to establish a DCI cell model. Four groups of cells, namely, control, model, naringenin‑treated, and positive control, were included. Cell viability (CCK‑8), ROS levels (DCFH‑DA/flow cytometry), IL‑6 and TNF‑α levels (ELISA), apoptosis (Annexin V‑FITC/PI), and STAT3 phosphorylation as well as Bax, Bcl‑2, and Caspase‑3 expression (western blot/RT‑qPCR) were assessed.

High glucose treatment significantly reduced cell viability; increased the ROS, MDA, IL‑6, and TNF‑α levels; enhanced apoptosis and STAT3 phosphorylation; upregulated Bax and Caspase‑3 expression; and decreased SOD and Bcl‑2 levels (all P < 0.01). Naringenin intervention restored cell viability, reduced ROS levels, ameliorated oxidative stress and inflammatory markers, decreased apoptosis, inhibited STAT3 phosphorylation, normalized Bax/Bcl‑2 expression, and downregulated Caspase‑3 expression (all P < 0.01).

Naringenin alleviates high glucose‑induced ROS‑dependent SH‑SY5Y cell injury and apoptosis by suppressing oxidative stress and inflammation and negatively regulating STAT3 signalling. This provides a cellular basis for its potential application in DCI prevention and treatment.