Palbinone alleviates diabetic retinopathy in STZ-induced rats by inhibiting NLRP3 inflammatory activity.

Abstract

Diabetic retinopathy (DR) is the primary cause of blindness and visual impairment in diabetes patients worldwide. However, laser and surgical therapies at DR have short-term effectiveness and cause side effects. Treatment with natural products is a reasonable alternative treatment for DR. The main objective of this investigation is to explore the efficacy of a bioactive compound such as palbinone (PB) in DR. Experimental rats were injected intraperitoneally with streptozotocin (STZ, 65 mg/kg), and these established experimental rats were treated with PB (20 mg/kg/bw) for 42 days. The observed results showedthat PB considerably reduced the proinflammatory cytokine(interleukin-18 [IL-18] and IL-1β) production as well as improved the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) particularly in the retinal region of STZ-induced DR rats. In addition, PB treatment improved nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation and enhanced the heme oxygenase-1 expression, and major antioxidants downregulatedNrf2in the damaged retina. Also, the expression levels of nod-like receptor family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, IL-1β, and apoptosis-associated speck-like protein containing CARD in the retinal region were notably upregulated in STZ-induced DR,which was eliminated by PB interference. PB administration exerted efficient antioxidant activities, Nrf2 pathway activation, and inhibition of NLRP3 inflammasome. This current investigation concluded that PB considerablyreduced the retinal inflammation and oxidative stress stimulated via high glucose, and also activated the antioxidative Nrf2 pathway and inhibited the NLRP3 inflammasome formation in rats.