The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines-The State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
FASEB J. 2019 Nov;33(11):11776-11790. doi: 10.1096/fj.201802614RRR. Epub 2019 Jul 31.
Blood-retinal barrier (BRB) breakdown is a typical event in the early stage of diabetic retinopathy (DR). This study aims to elucidate the protection of erianin, a natural compound isolated from Lindl, against DR development. Erianin alleviated BRB breakdown and rescued the reduced claudin1 and occludin expression in retinas from streptozotocin-induced diabetic mice. Erianin reduced microglial activation, ERK1/2 phosphorylation, NF-κB transcriptional activation, and the elevated TNF-α expression both and . ERK1/2 inhibitor U0126 abrogated NF-κB activation in d-glucose-treated BV2 cells. Erianin reduced cellular glucose uptake, and molecular docking analysis indicated the potential interaction of erianin with glucose transporter (GLUT)1. GLUT1 inhibitor (STF31) reduced the activation of the ERK1/2-NF-κB signaling pathway. Coculture with d-glucose-stimulated microglial BV2 cells and with TNF-α stimulation both induced inner BRB and outer BRB damage in human retinal endothelial cells and APRE19 cells, but erianin improved all these damages. In summary, erianin attenuated BRB breakdown during DR development by inhibiting microglia-triggered retinal inflammation reducing cellular glucose uptake and abrogating the subsequent activation of the downstream ERK1/2-NF-κB pathway. Moreover, erianin also alleviated BRB damage induced by TNF-α released from the activated microglia.-Zhang, T., Ouyang, H., Mei, X., Lu, B., Yu, Z., Chen, K., Wang, Z., Ji, L. Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.
血视网膜屏障 (BRB) 破坏是糖尿病视网膜病变 (DR) 早期的典型事件。本研究旨在阐明从 Lindl 中分离得到的天然化合物杨梅素对 DR 发展的保护作用。杨梅素可减轻 BRB 破坏，并挽救链脲佐菌素诱导的糖尿病小鼠视网膜中 Claudin1 和 Occludin 表达减少。杨梅素可减少小胶质细胞激活、ERK1/2 磷酸化、NF-κB 转录激活和 TNF-α 表达升高。ERK1/2 抑制剂 U0126 可阻断 d-葡萄糖处理的 BV2 细胞中 NF-κB 的激活。杨梅素可减少细胞葡萄糖摄取，分子对接分析表明杨梅素与葡萄糖转运蛋白 (GLUT)1 具有潜在相互作用。GLUT1 抑制剂 (STF31) 可减少 ERK1/2-NF-κB 信号通路的激活。与 d-葡萄糖刺激的小胶质细胞 BV2 细胞共培养和 TNF-α 刺激均可诱导人视网膜内皮细胞和 APRE19 细胞的内 BRB 和外 BRB 损伤，但杨梅素可改善所有这些损伤。总之，杨梅素通过抑制小胶质细胞触发的视网膜炎症、减少细胞葡萄糖摄取和阻断随后的下游 ERK1/2-NF-κB 通路激活，减轻 DR 发展过程中的 BRB 破坏。此外，杨梅素还可减轻由激活的小胶质细胞释放的 TNF-α 引起的 BRB 损伤。
