Abstract
An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neurodegeneration in chronic alcohol-induced mice. The neuroprotective effect was examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA) assays. As a result, AEEF reduced alcohol-induced cytotoxicity and oxidative stress. To evaluate the improvement of learning, memory ability, and spatial cognition, Y-maze, passive avoidance, and Morris water maze tests were conducted. The AEEF groups showed an alleviation of the decrease in cognitive function in alcohol-treated mice. Then, malondialdehyde (MDA) levels and the superoxide dismutase (SOD) content were measured to evaluate the antioxidant effect of AEEF in the brain tissue. Treatment with AEEF showed a considerable ameliorating effect on biomarkers such as SOD and MDA content in alcohol-induced mice. To assess the cerebral cholinergic system involved in neuronal signaling, acetylcholinesterase (AChE) activity and acetylcholine (ACh) content were measured. The AEEF groups showed increased ACh levels and decreased AChE activities. In addition, AEEF prevented alcohol-induced neuronal apoptosis via improvement of mitochondrial activity, including reactive oxygen species levels, mitochondrial membrane potential, and adenosine triphosphate content. AEEF inhibited apoptotic signals by regulating phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated protein kinase B (p-Akt), Bcl-2-associated X protein (BAX), and phosphorylated Tau (p-Tau). Finally, the bioactive compounds of AEEF were identified as caffeoylquinic acid (CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and chikusetsusaponin IVa using the UPLC-Q-TOF-MS system.
Highlights
Alcohol has been reported to cause various diseases such as fatty liver, liver cirrhosis, cardiovascular disease, cancer of various organs, and especially damage to the brain tissue [1, 2]
The dichlorodihydrofluorescein diacetate (DCF-DA) results (Figures 2(a) and 2(b)) indicated that the reactive oxygen species (ROS) content was increased by ethanol (129.28%) and H2O2 (115.25%) compared to the control group (100.00%), whereas AEEF treatment showed a remarkable reduction in oxidative stress induced by both ethanol and H2O2 at all concentrations
This study suggests that AEEF ameliorates chronic alcoholinduced neurodegeneration with the improvement of cognitive function and protection of brain tissue
Summary
Alcohol has been reported to cause various diseases such as fatty liver, liver cirrhosis, cardiovascular disease, cancer of various organs, and especially damage to the brain tissue [1, 2]. Alcohol is dehydrogenated to acetaldehyde, which is toxic in the central nervous system, by alcohol dehydrogenase. This acetaldehyde is decomposed to acetate by acetaldehyde dehydrogenase [5]. Oxidative stress causes secondary problems such as lipid peroxidation and Oxidative Medicine and Cellular Longevity mitochondria dysfunction, which lead to neuronal apoptosis in chronic alcohol-induced cognitive disorder [7]. The consumption of alcohol induces bacterial overgrowth and increases the serum concentration of the lipopolysaccharide (LPS) derived from the cell walls of intestinal gram negativebacteria [8]. Increased LPS in the blood induces inflammatory cytokines from Kupffer cells located in the liver [9]. Continuous stimulation of the microglia leads to neuronal inflammation, which leads to the apoptosis of brain cells [10]
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