Geniposide Attenuates Hyperglycemia-Induced Oxidative Stress and Inflammation by Activating the Nrf2 Signaling Pathway in Experimental Diabetic Retinopathy

Geniposide (GEN) is a natural antioxidant and anti-inflammatory product and plays an important role in the treatment of diabetes and diabetic complications. To explore the biological functions and mechanism of GEN in diabetic retinopathy (DR), we constructed the in vitro and in vivo model of DR by using primary cultured mouse retinal Müller cells and C57BL/6 mice, respectively. We found that GEN inhibited ROS accumulation, NF-κB activation, Müller cell activation, and inflammatory cytokine secretion both in vitro and in vivo, which is probably mediated through the Nrf2 pathway. Exendin (9-39) (EX-9), an antagonist of glucagon-like peptide-1 receptor (GLP-1R), abolished the protective effect of GEN on high glucose- (HG-) induced Müller cells. Additionally, GEN decreased hyperglycemia-induced damage to Müller cells and blood-retinal barrier in the retinas of mice with DR. We demonstrated that GEN was capable of protecting Müller cells and mice from HG-induced oxidative stress and inflammation, which is mostly dependent on the Nrf2 signaling pathway through GLP-1R. GEN may be an effective approach for the treatment of DR.