Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

Abstract

O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

Nutraceuticals for the Treatment of Diabetic Retinopathy

“…A post-translational modification (O-GlcNAcylation) of NF-κB has been observed in several pathologies, including DR [93]. An extract of Aralia elata (a plant traditionally used to treat diabetes in Eastern countries) containing phenolic compounds (3, 4-dihydroxybenzoic acid, chlorogenic acid, and caffeic acid) has been recently shown to reduce glial activation, to suppress NF-κB expression, and to decrease its O-GlcNAcylation in the retinas of STZ diabetic mice [94]. Finally, a fortified extract of red berries, Ginkgo biloba , and white willow bark containing carnosine and α-lipoic acid have been reported to attenuate the increase in TNFα levels in the retinas of STZ rats [95].…”

“…This result indicates that treatment with Lisosan G is able to protect both the inner and outer retina from diabetes-induced alterations [63]. Other compounds with documented neuroprotective effects in models of DR include zerumbone, whose anti-apoptotic effects correlate with improvement of retinal histological alterations and reduction of retinal thickness in diabetic rats [90], and Aralia elata , which protects mouse retinas from diabetes-induced decreases in retinal thickness, increases in TUNEL labeled ganglion cells, and increases in active caspase-3 [94]. Finally, an anti-apoptotic function, although not a direct neuroprotective effect, has been be attributed to taurine, a non-essential free aminoacid found in Lycium barbarum which has been reported to inhibit high glucose-promoted caspase-3 expression and activity in ARPE-19 cells [131].…”

O-GlcNAcylation in ischemic diseases

“…Additionally, the p65 subunit of NF-κB was O-GlcNAcylated in the ganglion cell layer of the retina. This is involved in hyperglycemia-induced NF-κB activation and RGC death in DR ( Kim et al, 2016 ; Kim et al, 2017 ). Diabetic retina is usually caused by diabetic macular edema, characterized by disruption of the blood-retinal barrier ( Tan et al, 2017 ).…”

Research progress in pharmacological effects of <italic>Aralia elata</italic>

“…此外，在糖尿病进展的后期，由于代谢异常、内分泌紊乱、免疫功能异常，常继发心血管系统疾病、肾损伤、神经损伤、视网膜病变。辽东楤木对糖尿病造成的并发症也具有良好的疗效。辽东楤木总皂苷可减缓糖尿病性心肌病早期阶段的进展 ［ 46 ］ ；可抑制因糖尿病导致的白内障形成，对视网膜神经节细胞具有良好的神经保护作用，主要是通过下调OGT、SREBP-1的表达、改善胰岛素抵抗、减少NF-κB p65亚基的 N -乙酰糖基化修饰等方式抑制视网膜神经节细胞的凋亡 ［ 47 - 49 ］ 。…”