Shikonin shows retinoprotective effects in diabetic rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways

Objective: To examine the effect of shikonin against streptozotocin (STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms. Methods: Intraperitoneal administration of STZ (65 mg/kg) was used for the induction of diabetic retinopathy in rats. Rats received oral administration of shikonin (10, 20, and 30 mg/kg). The blood glucose level, insulin, body weight, and organ weight were estimated. Advanced glycation end products (AGEs) levels in serum and lens as well as protein carbonyl content of the lens were determined. The parameters related to oxidative stress and inflammation, and the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were also measured. In addition, quantitative RT-PCR was performed to determine the mRNA expressions. Results: Shikonin treatment decreased glucose level and boosted insulin level, along with an increase in body weight and improved organ weight. It also lowered O 2 •- , ONOO - , serum and lens AGEs, and protein carbonyl content. Furthermore, shikonin treatment significantly alleviated oxidative stress and inflammation, as evidenced by reduced malonaldehyde, nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, cyclooxygenase-2, prostaglandin E 2 , protein carbonyl content, and nuclear factor kappa-B, and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase. Markedly decreased levels of ICAM-1 and VCAM-1, as well as heightened levels of Nrf2 and HO-1, were noticed after treatment with shikonin. Furthermore, the mRNA expressions of TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, RAGE, collagen IV , and fibronectin were significantly downregulated. Conclusions: Shikonin exhibits protective effects against STZ-induced diabetic retinopathy in rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways.