Ethyl Acetate Fraction from Persimmon (Diospyros kaki) Ameliorates Cerebral Neuronal Loss and Cognitive Deficit via the JNK/Akt Pathway in TMT-Induced Mice

Abstract

This study was conducted to assess the antioxidant capacity and protective effect of the ethyl acetate fraction from persimmon (Diospyros kaki) (EFDK) on H2O2-induced hippocampal HT22 cells and trimethyltin chloride (TMT)-induced Institute of Cancer Research (ICR) mice. EFDK had high antioxidant activities and neuroprotective effects in HT22 cells. EFDK ameliorated behavioral and memory deficits in Y-maze, passive avoidance and Morris water maze tests. Also, EFDK restored the antioxidant system by regulating malondialdehyde (MDA), superoxide dismutase (SOD) and reduced gluthathione (GSH), and the cholinergic system by controlling the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity and expression. EFDK enhanced mitochondrial function by regulating reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP). Ultimately, EFDK regulated the c-Jun N-terminal kinase (JNK)/protein kinase B (Akt) pathway and apoptotic pathway by suppressing the expression of tumor necrosis factor-alpha (TNF-α), phosphorylated insulin receptor substrate 1 (IRS-1pSer), phosphorylated JNK (p-JNK), phosphorylated tau (p-tau), phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-κB), Bcl-2-associated X protein (BAX) and cytosolic cytochrome c, and increasing the expression of phosphorylated Akt (p-Akt) and mitochondrial cytochrome c. This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway.

Chronic Alcohol Exposure Induced Neuroapoptosis: Diminishing Effect of Ethyl Acetate Fraction from Aralia elata

“…The level of ROS was determined by the DCF-DA method [16]. Cells seeded as 1 × 10 4 cells/well ( n = 5) in a 96-well black plate were incubated for 24 h. Vitamin C as a positive control or different concentrations of AEEF were treated to stabilize the seeded cells for 24 h. To confirm the protective effect against H 2 O 2 , every well except for the control was treated with 200 μ M H 2 O 2 for 3 h. Also, to investigate the protective effect against ethanol, every well except for the control was provided with 500 mM ethanol for 24 h after sample treatment for 3 h. Finally, 50 μ M DCF-DA in phosphate buffered saline (PBS) was treated in every well for 50 min to measure intracellular oxidative stress.…”

“…Cell viability was measured by the MTT method [16]. Cells were seeded and pretreated with EFAE or vitamin C in the same manner as the DCF-DA method in a 96-well plate.…”

<i>Bacopa monnieri</i> (L.) Ameliorates Cognitive Deficits Caused in a Trimethyltin-Induced Neurotoxicity Model Mice

“…Moreover, a treatment with TMT markedly enhanced neurogenesis in the dentate gyrus and olfactory bulb by inducing the proliferation of the endogenous neural stem/progenitor cells (NPCs) in each of these brain regions. 16,17) In rodents, TMT was found to cause hippocampus-dependent cognitive deficits, including short-term memory, as measured in the passive avoidance and novel object recognition testes [18][19][20][21] ; spatial working memory using the modified Y-and radial arm mazes 21,22) ; and spatial long-term memory using the Morris water maze. 21,23,24) Furthermore, behavioral studies demonstrated that TMT induced abnormal behaviors such as locomotor activity or depressive-like behaviors.…”

“…16,17) In rodents, TMT was found to cause hippocampus-dependent cognitive deficits, including short-term memory, as measured in the passive avoidance and novel object recognition testes [18][19][20][21] ; spatial working memory using the modified Y-and radial arm mazes 21,22) ; and spatial long-term memory using the Morris water maze. 21,23,24) Furthermore, behavioral studies demonstrated that TMT induced abnormal behaviors such as locomotor activity or depressive-like behaviors. 17,21,25) Therefore, TMT-intoxicated rodents are a useful model of degenerative diseases, such as Alzheimer's disease, the most common cause of dementia.…”

“…21,23,24) Furthermore, behavioral studies demonstrated that TMT induced abnormal behaviors such as locomotor activity or depressive-like behaviors. 17,21,25) Therefore, TMT-intoxicated rodents are a useful model of degenerative diseases, such as Alzheimer's disease, the most common cause of dementia. 26) The present study aimed to clarify the effects of BM on neuronal repair following hippocampal neuronal damage by using a mouse model of TMT-induced neuronal loss/selfrepair in the hippocampal dentate gyrus.…”