RESUMO
OBJECTIVE: To explore the role and mechanism of Yigan Mingmu Decoction (YGMMD) in preventing and treating diabetic macular edema (DME). METHODS: The bioactive compounds in YGMMD and their targets were screened using network pharmacology. Sprague Dawley (SD) rats were treated with the respective drugs: andomine, YGMMD-L, YGMMD-M, YGMMD-H for four weeks. Blood glucose, body weight, and morphologic indicators were measured, and hematoxylin and eosin (H&E) staining was used to assess retinal pathologic changes. Western blotting was used to monitor the expression of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT), pathway-related proteins aquaporin 4 (AQP4), inwardly rectifying potassium channel subtype 4.1 (Kir4.1), and phosphorylase extracellular regulated protein kinases (p-ERK1/2). Immunofluorescence was used to observe the expression levels of AQP4 and Kir4.1. Immunohistochemistry was performed to determine the expression of p-ERK1/2. RESULTS: Pharmacologic network analysis and molecular docking suggested that YGMMD treatment of DME regulates AQP4/Kir4.1. In vivo experiments showed that YGMMD had significant hypoglycemic effects and reduced retinal edema in Sprague Dawley (SD) rats: YGMMD-H downregulated AQP4 and p-ERK1/2 and upregulated p-AKT and Kir4.1. Findings suggest that the therapeutic effect of YGMMD in DME is probably due to the deregulation of AQP4/Kir4.1 expression through the ERK1/2-PI3K-AKT pathway. CONCLUSION: This study shows that YGMMD inhibits the activation of p-ERK1/2 while concurrently enhancing the expression of p-AKT, leading to a decrease in AQP4 levels and the upregulation of Kir4.1 expression. As a result, the balance in the retinal fluid clearance system is restored, effectively alleviating DME.
