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

Abstract

<p>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 showed&nbsp;that PB considerably reduced the proinflammatory cytokine&nbsp;(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 downregulated&nbsp;Nrf2&nbsp;in 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,&nbsp;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 considerably&nbsp;reduced 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.</p>