Protocatechualdehyde Attenuates Oxidative Stress in Diabetic Cataract via GLO1-Mediated Inhibition of AGEs/RAGE Glycosylation

Xiao Cheng¹Sixuan Zhao¹Yucai Chen²Jiawei Wang^1*Furong Han^1*

• ¹Beijing Tongren Hospital, Beijing, China
• ²Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China

1) Background: Protocatechualdehyde (PCA), a phenolic compound derived from Salvia miltiorrhiza, exhibits anti-proliferative and antioxidant properties. However, its molecular mechanisms in reducing oxidative stress in diabetic cataract (DC) remain unclear. This study systematically investigated the role of PCA in modulating glyoxalase-1 (GLO1) -dependent suppression of advanced glycation end products (AGEs) -receptor for AGEs (RAGE) axis activation and oxidative stress in DC models; (2) Methods: A galactose-induced DC rat model and high glucose-stimulated human lens epithelial cells (HLECs) were employed. Lens opacity was assessed using slit-lamp microscopy. GLO1, AGEs, and RAGE expression were analyzed through immunohistochemistry (IHC), immunofluorescence (IF), ELISA, and western blotting. Molecular docking was performed to validate PCA-GLO1 interactions; (3) Results: PCA administration (25 mg/kg) significantly alleviated lens opacity and epithelial cell disorganization in DC rats (p<0.01). In vitro, PCA (10 μM) restored HLEC viability under hyperglycemic conditions (p<0.05). Mechanistically, PCA upregulated GLO1 expression while suppressing AGE accumulation and RAGE activation in both models. Molecular docking revealed strong binding affinities between PCA and GLO1 (-CDOCKER energy: 26.41 kcal/mol); (4) Conclusions: PCA ameliorates DC progression by enhancing GLO1-mediated detoxification of AGE precursors, thereby inhibiting AGEs/RAGEdriven oxidative stress. These findings provide a foundation for PCA as a therapeutic candidate for DC.