Cirsium japonicum var. Maackii Improves Cognitive Impairment under Amyloid Beta25-35-Induced Alzheimer’s Disease Model

Abnormal production and degradation of amyloid beta (Aβ) in the brain lead to oxidative stress and cognitive impairment in Alzheimer’s disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aβ25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aβ25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aβ25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aβ25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.

Download Full-text

Krill Oil Attenuates Cognitive Impairment by the Regulation of Oxidative Stress and Neuronal Apoptosis in an Amyloid β-Induced Alzheimer’s Disease Mouse Model

Molecules ◽

10.3390/molecules25173942 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3942

Author(s):

Ji Hyun Kim ◽

Hui Wen Meng ◽

Mei Tong He ◽

Ji Myung Choi ◽

Dongjun Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mouse Model ◽

Neuronal Apoptosis ◽

Morris Water Maze Test ◽

Krill Oil ◽

Cognitive Improvement ◽

The Brain

In the present study, we investigated the cognitive improvement effects and its mechanisms of krill oil (KO) in Aβ25–35-induced Alzheimer’s disease (AD) mouse model. The Aβ25–35-injected AD mouse showed memory and cognitive impairment in the behavior tests. However, the administration of KO improved novel object recognition ability and passive avoidance ability compared with Aβ25–35-injected control mice in behavior tests. In addition, KO-administered mice showed shorter latency to find the hidden platform in a Morris water maze test, indicating that KO improved learning and memory abilities. To evaluate the cognitive improvement mechanisms of KO, we measured the oxidative stress-related biomarkers and apoptosis-related protein expressions in the brain. The administration of KO inhibited oxidative stress-related biomarkers such as reactive oxygen species, malondialdehyde, and nitric oxide compared with AD control mice induced by Aβ25–35. In addition, KO-administered mice showed down-regulation of Bax/Bcl-2 ratio in the brain. Therefore, this study indicated that KO-administered mice improved cognitive function against Aβ25–35 by attenuations of neuronal oxidative stress and neuronal apoptosis. It suggests that KO might be a potential agent for prevention and treatment of AD.

Download Full-text

Oxymatrine attenuates amyloid beta 42 (Aβ1–42)-induced neurotoxicity in primary neuronal cells and memory impairment in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0299 ◽

2019 ◽

Vol 97 (2) ◽

pp. 99-106 ◽

Cited By ~ 3

Author(s):

Peiliang Dong ◽

Xiaomeng Ji ◽

Wei Han ◽

Hua Han

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Neuronal Cells ◽

Morris Water Maze Test ◽

Dependent Manner ◽

Amyloid Beta 42

Amyloid beta 42 (Aβ1–42)-induced oxidative stress causes the death of neuronal cells and is involved in the development of Alzheimer’s disease. Oxymatrine (OMT) inhibits oxidative stress. In this study, we investigated the effect of OMT on Aβ1–42-induced neurotoxicity in vivo and in vitro. In the Morris water maze test, OMT significantly decreased escape latency and increased the number of platform crossings. In vitro, OMT markedly increased cell viability and superoxide dismutase activity. Moreover, OMT decreased lactate dehydrogenase leakage, malondialdehyde content, and reactive oxygen species in a dose-dependent manner. OMT upregulated the ratio of Bcl-2/Bax and downregulated the level of caspase-3. Furthermore, OMT inhibited the activation of MAP kinase (ERK 1/2, JNK) and nuclear factor κB. In summary, OMT may potentially be used in the treatment of Alzheimer’s disease.

Download Full-text

Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2019-0197 ◽

2020 ◽

Vol 31 (3) ◽

Cited By ~ 1

Author(s):

Ravinder Kaur ◽

Kudrat Randhawa ◽

Sanimardeep Kaur ◽

Richa Shri

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Allium Cepa ◽

Morris Water Maze Test ◽

Cholinesterase Inhibition ◽

Significant Activity ◽

Dependent Manner ◽

Model Of Alzheimer’S Disease ◽

The Brain

AbstractBackgroundAn earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study.MethodsIn vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer’s disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4′-O-glucoside content using a validated thin layer chromatography densitometric method.ResultsSTZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner.ConclusionsOur results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer’s disease.

Download Full-text

Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

Molecules ◽

10.3390/molecules26113442 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3442

Author(s):

Yaowared Chulikhit ◽

Wichitsak Sukhano ◽

Supawadee Daodee ◽

Waraporn Putalun ◽

Rakvajee Wongpradit ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Morris Water Maze Test ◽

Object Recognition Test ◽

Pueraria Mirifica ◽

Beneficial Effects ◽

Maze Test ◽

Y Maze ◽

Tnf Α ◽

17Β Estradiol

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

Download Full-text

Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer’s Disease in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5525306 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Nesrine S. El Sayed ◽

Esraa A. Kandil ◽

Mamdooh H. Ghoneum

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Gut Microbiota ◽

Neuronal Degeneration ◽

Amyloid Plaque ◽

Dependent Manner ◽

Insulin Degrading Enzyme ◽

Beneficial Effects ◽

Fermentation Technology

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

Download Full-text

Nrf2 Ablation Promotes Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3050971 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Peng Ren ◽

Jingwei Chen ◽

Bingxuan Li ◽

Mengzhou Zhang ◽

Bei Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Learning And Memory ◽

Spatial Learning ◽

Morris Water Maze Test ◽

Spatial Learning And Memory ◽

Related Factor ◽

Qrt Pcr

Introduction. Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) peptide and hyperphosphorylated tau protein. Accumulating evidence has revealed that the slow progressive deterioration of AD is associated with oxidative stress and chronic inflammation in the brain. Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2), which acts through the Nrf2/ARE pathway, is a key regulator of the antioxidant and anti-inflammatory response. Although recent data show a link between Nrf2 and AD-related cognitive decline, the mechanism is still unknown. Thus, we explored how Nrf2 protects brain cells against the oxidative stress and inflammation of AD in a mouse model of AD (APP/PS1 transgenic (AT) mice) with genetic removal of Nrf2. Methods. The spatial learning and memory abilities of 12-month-old transgenic mice were evaluated using a Morris water maze test. Hippocampal levels of Nrf2, Aβ, and p-tauS404 and of astrocytes and microglia were determined by immunostaining. Inflammatory cytokines were determined by ELISA and quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress was measured by 8-hydroxydeoxyguanosine immunohistochemistry, and the antioxidant response was determined by qRT-PCR. Results. The spatial learning and memory abilities of AT mice were impaired after Nrf2 deletion. Aβ and p-tauS404 accumulation was increased in the hippocampus of AT/Nrf2-KO mice. Astroglial and microglial activation was exacerbated, followed by upregulation of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Conclusion. Our present results show that Nrf2 deficiency aggravates AD-like pathology in AT mice. This phenotype was associated with increased levels of oxidative and proinflammatory markers, which suggests that the Nrf2 pathway may be a promising therapeutic target for AD.

Download Full-text

Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β-Secretase Enzymatic Activity Involved in Alzheimer’s Disease

BioMed Research International ◽

10.1155/2020/8934289 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Sayyad Ali ◽

Muhammad Hassham Hassan Bin Asad ◽

Fahad Khan ◽

Ghulam Murtaza ◽

Albert A. Rizvanov ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Biological Evaluation ◽

Morris Water Maze Test ◽

Pharmacokinetic Parameters ◽

The Novel ◽

Object Recognition Test ◽

Promising Target

Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer’s disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50=97±0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p<0.05). Improved pharmacokinetic parameters, viz., Log Po/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD.

Download Full-text

Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Cancers ◽

10.3390/cancers12123842 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3842

Author(s):

Harvey R. Fernandez ◽

Ashima Varma ◽

Sarah A. Flowers ◽

George William Rebeck

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Cognitive Impairment ◽

Blood Brain Barrier ◽

Cancer Chemotherapy ◽

Apoe Genotype ◽

Brain Barrier ◽

Blood Brain

Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.

Download Full-text