Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice

Abstract

Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice. AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes. Protein levels of O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory elementbinding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting. Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis. Interaction between ChREBP and OGT was assessed using coimmunoprecipitation analysis. AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas. AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas. Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas. Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was significantly decreased in diabetic mice treated with AES extract. These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.