biostudies-literatureZhang TNational Natural Science Foundation of China11776-11790https://www.ebi.ac.uk/biostudies/studies/S-EPMC6902687biostudies-literatureUnknown33(11)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 <i>Dendrobium chrysotoxum</i> 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 <i>in vitro</i> and <i>in vivo</i>. 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 (GFASEB journal : official publication of the Federation of American Societies for Experimental BiologyErianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells <i>via</i> inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.PMC6902687815736798132205381173517Zhang TChen KOuyang HMei XJi LYu ZWang ZLu BfalseErianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells <i>via</i> inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.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 <i>Dendrobium chrysotoxum</i> 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 <i>in vitro</i> and <i>in vivo</i>. 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 (G2019-01-01T00:00:00Z2019 Nov2026-05-04T03:43:57.878Z2020-11-19T13:35:31ZS-EPMC69026873136527810.1096/fj.201802614RRR10.1096/fj.201802614rrr