<b><i>Aralia elata</i></b> Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

Abstract

Background/Aims: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. Methods: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. Results: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. Conclusions: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.

Medicinal plants for diabetes associated neurodegenerative diseases: A systematic review of preclinical studies

“…Kim et al (2015c) during a study on diabetic mice indicated that A. elata could modulate diabetic retinal neurodegeneration by prevention of RGC apoptosis and by decrease of TonEBP , AR and NF‐κB expression. Therefore, this herb is a promising agent for treatment of diabetes retinopathy due to its inhibition activity on neuronal toxicity and inflammation, leading to neuronal death (Kim et al, 2015c).…”

How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?

“…Thus, targeting the regulatory network of NFAT5 may be an alternative approach to treat diabetic nephropathy. In this regard, the extract from plant Aralia elata has been recently shown to prevent neuronal death by downregulating NFAT5 and AR in mice with diabetic retinopathy, although which regulatory pathway it affects remains unknown [46] .…”

Inhibitory effect of an ethanol extract mixture of Aralia elata leaf, Chaenomeles sinensis fruit and Glycyrrhizae radix on Aβ (25–35)-induced memory impairment

“…In previous reports, Chaenomeles sinensis fruit was demonstrated to show neuroprotective effects against Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)-induced neurotoxicity in in vivo and in vitro [25]. Glycyrrhizae radix prevented Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)-induced neurotoxicity in cultured neurons [26]. Glycyrrhizae radix have been proved for its memory-enhancing effect and its anticholinesterase activity [23,27].…”

“…Glycyrrhizae radix have been proved for its memory-enhancing effect and its anticholinesterase activity [23,27]. Studies have reported neuronal protective effects of Aralia elata in some animal models [13,28]. Therefore, it was hypothesized that mixture of these three plants, possessing anti-oxidant and anti-inflammatory activities, might show more effective and synergistic neuroprotective effect with the reduction of possible individual toxicity due to large quantity.…”

“…The present study was conducted to confirm the inhibitory effect of an ethanol extract mixture of Aralia elata, Chaenomeles sinensis fruit, and Glycyrrhizae radix, which was named as ACG, on memory impairment induced by a single intracerebroventricular (i.c.v.) injection of Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) in mouse model of AD-type amnesia [29].…”