Proanthocyanidins attenuate the high glucose-induced damage of retinal pigment epithelial cells by attenuating oxidative stress and inhibiting activation of the NLRP3 inflammasome

Diabetic retinopathy (DR) is a common diabetic complication known to cause vision impairment and blindness. Previous studies have demonstrated that proanthocyanidins (PACs), polyphenols that are naturally found in several plants and fruits, have powerful antioxidant and anti-inflammatory effects on various cells. However, the effects and underlying mechanism of PACs against DR pathogenesis remain unknown. Here, we investigated the proliferation, apoptosis, and mechanisms of ARPE-19 cells in response to oxidative stress and inflammation under high-glucose conditions with or without PACs treatment. The Cell-Counting Kit-8 assay and western blot analysis showed that treatment with 10 mu l PACs significantly increased cell proliferation and the expression level of Bcl-2 in ARPE-19 cells under high-glucose conditions. Moreover, PACs attenuated the high glucose-induced apoptosis, and the increased expression levels of caspase-3 and Bax. Under high-glucose conditions, the generation of reactive oxygen species (ROS) and levels of malondialdehyde increased, whereas the superoxide dismutase content decreased. Moreover, the expression level of the NLRP3 inflammasome, and the release of interleukin 1 beta (IL-1 beta) and IL-18 increased. PACs reversed all of these high glucose-induced effects on ARPE-19 cells. Additionally, exposure to nigericin sodium salt, an agonist of the NLRP3 inflammasome, upregulated expression of the NLRP3 inflammasome accompanied by the release of IL-1 beta and IL-18. Again, treatment with PACs markedly downregulated these effects. Collectively, these results demonstrate that PACs can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR.