Abstract

Background: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. EJPs (Erjing Pills) are believed in Traditional Chinese Medicine to have the effects of a nourishing essence and a brightening of the eyes, but the specific effect on DR remains unclear. This study aims to investigate the therapeutic effects and underlying mechanisms of EJPs on DR. Methods: The chemical profile of EJPs was characterized by UHPLC-MS. Network pharmacology and molecular docking were employed to predict its active ingredients and potential targets. A DR rat model was induced by streptozotocin. Retinal morphology and function were assessed by OCT, FFA, and H&E staining. The expressions of proteins and mRNAs related to the AGE-RAGE pathway, oxidative stress, inflammation, and tight junctions were detected by Western blot, qPCR, and ELISA. Results: LC-MS and network pharmacology analysis identified 638 common targets between EJPs and DR, with core targets including SRC, AKT1, and MAPK1, primarily enriched in the AGE-RAGE signaling pathway. Molecular docking confirmed strong binding (binding energy < -5.0 kcal/mol) between key EJP constituents and core targets. In vivo, EJP treatment significantly alleviated retinal vascular leakage, improved retinal thickness, and alleviated histopathological damage. In addition, EJPs downregulated the AGEs-RAGE/NF-κB axis and pro-inflammatory cytokines while enhancing antioxidant defenses and tight junction proteins in the retinas of DR rats. Conclusions: EJPs ameliorate DR by protecting the blood-retinal barrier and modulating the AGE-RAGE/oxidative stress/inflammation network, demonstrating a multi-component, multi-target, and multi-pathway mechanism. This study provides a mechanistic basis for the potential application of EJPs in DR management.