Paeonol attenuates oxidative stress and inflammation in experimental diabetic retinopathy by regulating the Nrf2/NF-κB signaling

This study aimed to investigate the protective mechanism of paeonol against diabetic retinopathy (DR) via modulation of the Nrf2/NF-κB signaling pathway. Primary mouse retinal Müller cells exposed to high glucose (HG) and streptozotocin-induced diabetic mice were used as in vitro and in vivo models, respectively. Key techniques included RT-qPCR, Western blot, DCFH-DA-based ROS assays, and ELISA. Paeonol (40-80 μg/ml) significantly reduced HG-induced ROS accumulation (p < 0.01) and restored Nrf2 nuclear translocation, upregulating antioxidant genes HO-1 and NQO1 (p < 0.01). It suppressed NF-κB activation (p-IκBα and p-p65 reduction; p < 0.001) and proinflammatory cytokines (TNF-α, IL-1β, IL-6; p < 0.01) in Müller cells and diabetic retinas. Blood-retinal barrier (BRB) integrity was preserved via upregulation of tight junction proteins (claudin-5, occludin, ZO-1; p < 0.01). In conclusion, paeonol attenuates DR progression by activating Nrf2-mediated antioxidant responses and inhibiting NF-κB-driven inflammation, highlighting its potential as a novel therapeutic agent for DR.