Oridonin attenuates diabetic retinopathy progression by suppressing NLRP3 inflammasome pathway

Oridonin (Ori) possesses anti-inflammatory properties. However, its potential to treat diabetic retinopathy (DR) remains unclear. This study aimed to investigate the retinal protective function of Ori and the underlying mechanism. In streptozotocin-induced mice, Ori alleviated visual impairment, reduced retinal and vascular lesions, protected the neuroretinal structure, reversed retinal nerve layer thickening. Addtionnally, Ori reduced TNF-α and IL-1β levels in the peripheral blood, and suppressed retinal NLRP3 inflammasome-related inflammatory factor. In vitro, human retinal endothelial cells (hRECs) were stimulated by high glucose (HG). HG-stimulated hRECs activated the NLRP3 inflammasome, whereas Ori significantly alleviated pyroptosis by enhancing cell viability and reducing IL-1β levels in the supernatant. Ori also inhibited NF-κB/NLRP3 inflammasome pathway. NEK7 depletion alleviated NLRP3 inflammasome activation and, to some extent, mimicked the role of Ori. Indeed, Ori reversed NLRP3 inflammasome activation by suppressing NEK7–NLRP3 interaction. Therefore, Ori may serve as a potential therapeutic agent for attenuating DR progression.