Department Ophthalmology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
Department Opthalmology, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
J Biochem Mol Toxicol. 2020 Jul;34(7):e22489. doi: 10.1002/jbt.22489. Epub 2020 Mar 22.
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 that 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 downregulated Nrf2 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, 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 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.
糖尿病视网膜病变（DR）是全球糖尿病患者失明和视力障碍的主要原因。然而，激光和手术治疗 DR 的效果持续时间短，且会产生副作用。使用天然产物进行治疗是 DR 的一种合理替代治疗方法。本研究的主要目的是探讨一种生物活性化合物，如胡椒酮（PB），在 DR 中的疗效。实验大鼠经腹腔注射链脲佐菌素（STZ，65mg/kg），建立实验性 DR 大鼠模型，并给予 PB（20mg/kg/bw）治疗 42 天。观察结果表明，PB 可显著减少促炎细胞因子（白细胞介素-18[IL-18]和 IL-1β）的产生，并改善抗氧化酶（超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）的活性，尤其是在 STZ 诱导的 DR 大鼠的视网膜区域。此外，PB 治疗可增加核因子红细胞 2 相关因子 2（Nrf2）的积累，增强血红素加氧酶-1 的表达，并下调主要抗氧化剂在受损视网膜中的 Nrf2。同样，在 STZ 诱导的 DR 大鼠的视网膜区域，NOD 样受体家族 pyrin 结构域包含 3（NLRP3）、切割的半胱天冬酶-1、IL-1β和凋亡相关斑点样蛋白包含 CARD 的表达水平显著上调，而这些上调被 PB 干扰所消除。PB 给药具有有效的抗氧化活性、Nrf2 通路激活和 NLRP3 炎性小体抑制作用。本研究表明，PB 可显著减轻高葡萄糖刺激的视网膜炎症和氧化应激，并激活抗氧化 Nrf2 通路，抑制 NLRP3 炎性小体的形成。
