Protective effects of sulforaphane on diabetic retinopathy: activation of the Nrf2 pathway and inhibition of NLRP3 inflammasome formation

Abstract

Sulforaphane (SFN) is abundant in cruciferous plants, providing significant protection against many chronic diseases. With the aim of clarifying the efficacy of sulforaphane in diabetic retinopathy (DR), a series of systematic studies were carried out in the present study. Male Sprague Dawley rats were intraperitoneally injected with streptozotocin (STZ, 65 mg/kg), and those with confirmed diabetes mellitus were given different doses of SFN (0.5 and 1 mg/kg/d) for 12 weeks. In vitro, Müller cells exposed to 25 mM glucose were treated with 2.5 µM SFN. The results indicated that SFN significantly reduced the generation of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and enhanced the activity of antioxidant enzymes (GSH, SOD, and CAT) in the retina of STZ rats. Further, SFN enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1 and NQO1, two major antioxidants downstream to Nrf2, in the injured retina. In addition, retinal expression levels of NLRP3, cleaved caspase-1 p20, IL-1β p17, and ASC were dramatically increased in STZ-induced DR, and this was abolished by SFN intervention. In vitro, high glucose-induced inflammation and oxidative stress damage in Müller cells were attenuated by SFN. SFN also exerted antioxidant effects, activated the Nrf2 pathway, and inhibited the NLRP3 inflammasome in Müller cells. In conclusion, our work demonstrates that SFN attenuates retinal inflammation and oxidative stress induced by high glucose and activates the antioxidative Nrf2 pathway and inhibits the formation of the NLRP3 inflammasome in vivo and in vitro.