Yigan Mingmu Decoction inhibits diabetic macular edema through regulating Kir4.1/AQP4 axis: a study based on network...

To explore the role and mechanism of Yigan Mingmu Decoction (YGMMD) in preventing and treating diabetic macular edema (DME).

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.

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.

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.