Procyanidin B2 Protects TR-iBRB2 Cells Against Hyperglycemia Stress by Attenuating Oxidative Stress and Inflammasome Activation via Regulation of Redoxosomes/NF-kB Signaling

Abstract

Background: Microvascular dysfunction is a hallmark of diabetic retinopathy (DR), which may lead to visual impairment and blindness. Procyanidin B2 (PB2) is a subclass of flavonoids and widely known due to its anti-oxidant and anti-inflammatory effects. However, little is known about the effect of PB2 on hyperglycemia stress-induced retinal microvascular dysfunction. Objective: The purpose of this study was to investigate the effect of PB2 against hyperglycemia stress in rat retinal capillary endothelial cells (TR-iBRB2) as well as the underpinning mechanism. Methods: Cell viability was determined using MTT assay. ROS, NOX activity analysis, Western blot analysis, Immunofluorescence analysis were applied in the study. Results: The results showed that PB2 pre-treatment significantly reduced high glucose-induced cytotoxicity in TR-iBRB2 cells by suppressing oxidative stress and inflammasome activation. Mechanistical study revealed that redoxosomes was formed and activated in TR-iBRB2 cells upon hyperglycemia stress, which then resulted in activation of NF-κB and thus induction of oxidative stress and inflammasomes activation. However, PB2 pre-treatment dose-dependently attenuated the above events, indicating the protective effect of PB2 against hyperglycemia stress was achieved by regulating redoxosomes/NF-kB signaling. Conclusion: Our findings may contribute to the potential clinical use of PB2 in treating DR and suggest redoxosomes/NF-kB signaling may be a potential therapeutic target of this disease.