Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells via inhibiting hyperglycemia‐mediated ERK1/2–NF‐κB 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‐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. FASEB J. 33, 11776‐11790 (2019). http://www.fasebj.org

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation

“…Erianin has been studied mainly for its antiangiogenic properties. In preclinical studies, 100 mg/kg per day of erianin induced growth delay in tumors [199]. In 2015, erianin was first introduced as a DR therapy option, by inhibiting the NF-κβ signaling pathway, thus inhibiting retinal…”

“…Oxidative Medicine and Cellular Longevity inflammation in preclinical studies [198,199]. Nevertheless, clinical studies are still needed to assess its clinical relevance in DR and its potential use as a concomitant therapy in this disease.…”

Identification of the metabolites of erianin in rat and human by liquid chromatography/electrospray ionization tandem mass spectrometry

“…been demonstrated to alleviate diabetic retinopathy by reducing retinal inflammation inhibited by microglia cells via inhibiting hyperglycemia-mediated ERK1/2-NF-κB signal pathway. 13 Erianin also showed a protective effect against high glucose-induced oxidative injury in renal tubular epithelial cells. 14 Although the pharmacological effects have been investigated extensively, the pharmacokinetics and metabolism of erianin have been studied insufficiently.…”

“…Therefore, erianin has the potential to be developed as an anticancer drug. Besides its antitumor activity, erianin has been demonstrated to alleviate diabetic retinopathy by reducing retinal inflammation inhibited by microglia cells via inhibiting hyperglycemia‐mediated ERK1/2‐NF‐κB signal pathway . Erianin also showed a protective effect against high glucose‐induced oxidative injury in renal tubular epithelial cells …”

LC–MS/MS method for the determination of erianin in rat plasma: Application to a pharmacokinetic study

“…Previous studies have reported that erianin has antiangiogenic and antitumor activities (Gong, Fan, Liu, et al, 2004; Gong, Fan, Wu, Hu, & Wang, 2004; Sun et al, 2016; Li, Wang, & Liu, 2001; Wang et al, 2016). The antitumor mechanism mainly involves inducing cancer cell apoptosis and modulating the ROS/JNK signaling pathways (Zhang, Ouyang, et al, 2019; Zhu et al, 2019). In addition, erianin has been demonstrated to alleviate diabetic retinopathy by reducing retinal inflammation inhibited by microglia cells via inhibiting the hyperglycemia‐mediated ERK1/2‐NF‐ κ B signal pathway (Zhang, Zhang, Wei, & Liu, 2019).…”