Sodium Aescinate Alleviates Diabetic Retinopathy in Rats by Inhibiting the AGE-RAGE Signaling Pathway

Abstract

Background: Diabetic retinopathy (DR) is a complication of diabetes that impacts the vision and quality of life of patients. Sodium aescinate (SA) has been widely used in resisting exudation and treating inflammation and vascular diseases, which is consistent with the disease symptoms of DR. However, the therapeutic effect and molecular mechanism of SA on DR are lacking. Therefore, this study is aimed at examining the palliative impact of SA on DR rats induced by streptozotocin (STZ). Methods: DR model was established by injecting STZ (80 mg/kg) into the Sprague Dawley (SD) rats (7-week-old). Later, SA was administered via the tail vein at a dosage of 1 mg/kg/per, 7 days/cycle, totaling 21 days. During this period, the changes in the rats body weight and blood sugar levels were observed, and their glucose tolerance was monitored. The fundus conditions of the rats were then examined using fundus photography, focusing on the diameter and permeability of blood vessels. Retinal pathology was assessed using hematoxylin-eosin (HE) staining, and the changes in DR-related markers vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) in the retinas were assayed. The changes in reactive oxygen species (ROS), lipid peroxidation (Lip-ROS), malondialdehyde (MDA), glutathione (GSH), and insulin-like growth factor 1 (IGF1) in retinal protein, as well as the changes of IGF1 in the serum, were also evaluated. Additionally, the changes in the advanced glycation end products (AGE)-receptor for AGEs (RAGE) signaling pathway were investigated. Results: The treatment group with SA slowed down the diameter of fundus blood vessels and reduced angiogenesis in DR. It inhibited the expression of VEGF and TNF-α. At the same time, SA could also inhibit the activation of ROS, MDA, GSH, and IGF1, and reduce the protein content of IGF1. Additionally, the expression of AGE and RAGE in the advanced glycation end products (AGE)-receptor for AGEs (RAGE) signaling pathway was decreased, and the phosphorylated Janus kinase-signal transd ucer and activator of transcription 3 (JAK/STAT3) in its downstream pathway was also downregulated. Conclusions: SA has the capacity to diminish DR by inhibiting oxidative stress and AGE-RAGE signaling pathway.