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 Dendrobium chrysotoxum 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 in vitro and in vivo. 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 via 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 via inhibiting
hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.