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Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells via inhibiting hyperglycemia-mediated ERK1/2-NF-?B signaling pathway.

ABSTRACT: 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-?B transcriptional activation, and the elevated TNF-? expression both in vitro and in vivo. ERK1/2 inhibitor U0126 abrogated NF-?B 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-?B signaling pathway. Coculture with d-glucose-stimulated microglial BV2 cells and with TNF-? 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-?B pathway. Moreover, erianin also alleviated BRB damage induced by TNF-? 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-?B signaling pathway.

SUBMITTER: Zhang T

PROVIDER: S-EPMC6902687 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells <i>via</i> inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.

Zhang Tianyu T Ouyang Hao H Mei Xiyu X Lu Bin B Yu Zengyang Z Chen Kaixian K Wang Zhengtao Z Ji Lili L

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20190731 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 ...[more]

PMID: 31365278

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Project description:BackgroundThe steroid hormone estrogen (17-β-estradiol, E2) provides neuroprotection against cerebral ischemic injury by activating estrogen receptors. The novel estrogen receptor G protein-coupled receptor 30 (GPR30) is highly expressed in the brain and provides acute neuroprotection against stroke. However, the underlying mechanisms remain unclear.MethodsIn this study, ovariectomized female mice were subjected to middle cerebral artery occlusion (MCAO), and E2, G1, and ICI182780 were administered immediately upon reperfusion. The infarction volume, neurological scores, and neuronal injuries were examined. Primary microglial cells were subjected to oxygen-glucose deprivation (OGD), and the drugs were administered immediately upon reintroduction. The pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in penumbra and microglia were assessed by ELISA. The cell viability and lactose dehydrogenase (LDH) release of neurons co-cultured with microglia were analyzed using cell counting kit-8 (CCK8) and LDH release assays. Microglial activation as well as GPR30, Iba1, and Toll-like receptor 4 (TLR4) protein expression and TLR4 mRNA expression were detected. Additionally, NF-κB activity was detected in lipopolysaccharide (LPS)-activated microglia after the activation of GPR30.ResultsGPR30 was highly expressed in microglia and significantly increased after ischemic injury. The activation of GPR30 significantly reduced the infarction volume, improved the neurological deficit, and alleviated neuronal injuries. Moreover, GPR30 activation significantly reduced the release of TNF-α, IL-1β, and IL-6 from ischemic penumbra and microglia subjected to OGD and alleviated neuronal injury as assessed using the CCK8 and LDH assays. Finally, the activation of GPR30 relieved microglial activation, reduced Iba1 and TLR4 protein expression and TLR4 mRNA levels, and inhibited NF-κB activity.ConclusionsMicroglial GPR30 exerts acute neuroprotective effects by inhibiting TLR4-mediated microglial inflammation, which indicates that GPR30 may be a potential target for the treatment of ischemic stroke.

Dataset Information

Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells via inhibiting hyperglycemia-mediated ERK1/2-NF-?B signaling pathway.

Publications

Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells <i>via</i> inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway.

Similar Datasets

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