Scutellarin attenuates high glucose-induced edema and inflammation in retinal Müller cells via AQP4/Kir4.1 restoration and TLR4/MyD88/NF-κB inhibition

Abstract

Diabetic retinopathy (DR) is a metabolic eye disease closely linked to inflammation and oxidative stress, potentially causing vision decline or blindness. Scutellarin (SCU), a major flavonoid extracted from Erigeron breviscapus, possesses anti-inflammatory and antioxidant properties; however, its protective mechanisms against retinal Müller cell (RMC) injury in DR remain unclear. To investigate the protective effects and underlying mechanisms of SCU against high-glucose(HG)-induced edema and inflammation in retinal Müller cells (RMCs). Primary RMCs were isolated from newborn 3–5-day-old Sprague-Dawley (SD) rats and exposed 100 mmol/L HG to establish an in vitro injury model. Groups included control, model (HG), low-dose (HG+25 μmol/L SCU), and high-dose (HG+50 μmol/L SCU). Cell viability, migration capacity, Na + -K + -ATPase activity, and apoptosis were assessed using CCK-8 assays, scratch wound healing assays, enzymatic activity assays, and flow cytometry, respectively. The expression and distribution of AQP4, Kir4.1, and molecules associated with the TLR4/MyD88/NF-κB/VEGFA pathway were evaluated via immunofluorescence, Western blot, and qRT-PCR. HG exposure significantly suppressed RMC viability, induced apoptosis, disrupted the functional coupling of AQP4/Kir4.1, and activated the TLR4/MyD88/NF-κB/VEGFA signaling pathway. SCU treatment dose-dependently reversed these pathological changes, restored Na + -K + -ATPase activity and the expression balance of AQP4/Kir4.1, and inhibited the excessive activation of the inflammatory pathway. The protective effects of SCU are significantly associated with the restoration of AQP4/Kir4.1 homeostasis and the suppression of the TLR4/MyD88/NF-κB/VEGFA pathway, suggesting its potential as a multi-target candidate drug for delaying the progression of DR.