Effect of Donepezil on Vascular Dementia in Rats via PI3K/AKT Pathway

2022 ◽  
Vol 12 (5) ◽  
pp. 1046-1052
Author(s):  
Jianmin Zhang ◽  
Qianwen Zhu ◽  
Xingnan Wang ◽  
Jian Wang
Keyword(s):  
Oxidative Stress ◽  
Vascular Dementia ◽  
Learning And Memory ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Ros Production ◽  
Sod Activity ◽  
Ht22 Cells ◽  
Stress Injury

Background: Previous studies have shown that Donepezil has therapeutic effects on vascular dementia (VD). PI3K/AKT involves in oxidative stress injury and cell apoptosis. This study investigated whether Donepezil affects the neurological function and apoptosis of VD mice via PI3K/AKT signaling. Methods: Mice were assigned into Sham group, VD group, VD+Donepezil groupfollowed by analysis of mice learning and memory ability by Water maze test, p-AKT expression by Western blot, Caspase-3 activity, MDA content, SOD activity and GSH-Px in hippocampus. HT22 cells were cultured and separated into control group, I-R group and I-R+Donepezil group followed by measuring p-AKT level, ROS content and apoptosis. Results: Learning and memory abilities of VD group mice were significantly decreased, Caspase-3 activity and MDA in brain tissue were significantly increased, along with decreased SOD activity, GSH-Px and p-AKT level. Donepezil treatment can significantly improve VD mice learning and memory ability, reduce Caspase-3 activity and MDA in brain tissue, increase SOD activity, GSH-Px and p-AKT level. In vitro, I-R treatment significantly induced apoptosis of HT22 cells, increased ROS production and decreased p-AKT level. Donepezil treatment could up-regulate p-AKT in HT22 cells and reduce apoptosis and ROS production in HT22 cells. Conclusion: Donepezil improves the function of brain nerve in VD mice through regulating PI3K/AKT pathway, thus reducing oxidative stress injury and apoptosis of brain nerve cells.

scholarly journals Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Wenyuan Li ◽  
Wei Li ◽  
Yan Leng ◽  
Yonghong Xiong ◽  
Rui Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Akt Pathway ◽  
Myocardial Cells ◽  
Stress Injury ◽  
Apoptosis Rate ◽  
Oxidative Stress Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Ischemic heart disease is the main cardiovascular complication of diabetes patients which is mainly caused by oxidative stress. DJ-1 is the key regulator for myocardial protection through inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and activating Akt (also known as PKB or protein kinase B). This research is to investigate whether the antioxidant N-acetylcysteine (NAC) could alleviate diabetic myocardial ischemia/reperfusion (I/R) injury by the protective molecule DJ-1. DJ-1 in rat myocardial H9c2 cells and cardiac tissue was respectively knocked down by siRNA and adeno-associated virus (AAV). From the present study, it could be found that compared with high glucose (HG)-normal (N)/DM group, hypoxia/reoxygenation (H/R) or I/R injury can aggravate oxidative stress injury and apoptosis rate of myocardial cells, inhibit the expression of Bcl-2, activate the BAX and cleaved caspase-3 (c-caspase-3) protein and PTEN/Akt pathway. However, in the groups of HG-N, DM, HG-N+I/R and DM+I/R, NAC can significantly reduce oxidative stress injury and apoptosis rate of myocytes, promote the Bcl-2 and DJ-1 molecules, inhibit BAX and c-caspase-3 protein and PTEN/Akt pathway. Compared with HG-N+I/R+NAC and DM+I/R+NAC groups, the oxidative stress injury, apoptosis rate of myocardial cells and heart tissues increased after the knockdown of DJ-1, the expression of Bcl-2 and DJ-1 were inhibited, the BAX and c-caspase-3 expression was increased, and PTEN/Akt pathway was activated. Taken together, the findings suggest that NAC can reduce I/R injury in diabetic myocardium by up-regulating the PTEN/Akt pathway through the level of DJ-1.

scholarly journals Effect of chronic hypoxia and hypercapnia on learning and memory function in mice and the expression of NT and CGRP in brain

2018 ◽  
Vol 16 ◽  
pp. 205873921881895 ◽  
Author(s):  
Hangyu Xu ◽  
Hao Xu
Keyword(s):  
Learning And Memory ◽  
Brain Tissue ◽  
Chronic Hypoxia ◽  
Memory Function ◽  
Normal Pressure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Sod Activity ◽  
Stress Injury ◽  
Experimental Group

The aim of this study is to investigate the effects of chronic hypoxia and hypercapnia on learning and memory function of mice and the expression of neurotensin (NT) and calcitonin gene–related peptide (CGRP) in mice brain. A total of 30 C57BL/6J male mice were randomly divided into normoxia control group (control group, n = 15) and chronic hypoxia and hypercapnia stress group (experimental group, n = 15). The control group was kept under normal temperature and pressure conditions, while the experimental group was kept in a chamber at normal pressure, hypoxia and hypercapnia for 8 h daily and 6 days a week for 4 weeks. On the 28th day, the learning and memory ability of mice was examined by 8-arm maze. The content of 8-hydroxy-deoxyguanosine (8-OHdG) in brain was detected by enzyme-linked immunosorbent assay (ELISA) analysis. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined by spectrophotometry, and the derangement of hippocampal ultrastructures and numbers of apoptotic neurons were observed by microscope. The expression of NT and CGRP in brain tissue was observed by immunochemistry. Compared to control group, the content of 8-OHdG in hippocampal and serum MDA were significantly increased by 1.3 and 1.78 times, while the activity of SOD in serum was decreased by 27.28% in experimental group. Besides, the cellular structure of the hippocampus was disorderly arranged, the shape is irregular and the quantity is markedly reduced obviously in experimental group. In addition, the content of NT and CGRP in brain tissue was higher in experimental group than in control group ( P < 0.05). The stress of chronic hypoxia and hypercapnia not only can induce learning and memory disorders in mice which may be related to increased neuronal apoptosis and oxidative stress injury but also can increase the expression of NT and CGRP in brain tissue which may have some impact on gastrointestinal motility in mice.

scholarly journals Synergistic Protective Effect of Curcumin and Resveratrol against Oxidative Stress in Endothelial EAhy926 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xian Zhou ◽  
Sualiha Afzal ◽  
Yan-Fang Zheng ◽  
Gerald Münch ◽  
Chun Guang Li
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Caspase 3 ◽  
Combination Index ◽  
New Combination ◽  
Ros Production ◽  
Protective Effects ◽  
Sod Activity ◽  
Index Model ◽  
Induced Changes

Curcumin (C) and resveratrol (R) are two well-known nutraceuticals with strong antioxidant activity that can protect cells from oxidative stress. This study aims to investigate the synergy of CR combinations in protecting human endothelial EAhy926 cells against H2O2-induced oxidative stress and its related mechanisms. C and R as individual compounds as well as CR combinations at different ratios were screened for their protective effects against H2O2 (2.5 mM) induced cell death assessed by cell viability assays. The synergistic interaction was analysed using the combination index model. The effects of optimal CR combinations on caspase-3 activity, ROS level, SOD activity, NAD cellular production, expression of Nrf2 and HO-1, and Nrf2 translocation were determined. CR combinations produced a synergistic protection against that of H2O2-induced changes in cell viability, caspase-3 activity, and ROS production. The strongest effect was observed for CR with the ratio of 8 : 2. Further experiments showed that CR 8 : 2 exhibited significantly greater effects in increasing Nrf2 translocation and expressions of Nrf2 and HO-1 proteins, as well as SOD activity and total cellular NAD production, than that of C or R alone. The findings demonstrate that combination of C and R produced a strong synergy in activity against H2O2-induced oxidative stress in EAhy926 cells. The mechanism of this synergy involves the activation of Nrf2-HO-1 signaling pathway and promotion of antioxidant enzymes. Further studies on CR synergy may help develop a new combination therapy for endothelial dysfunction and other conditions related to oxidative stress.

Rehmanniae Decoction Improve Brain Function in Vascular Dementia Rats Through Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway

2020 ◽  
Vol 10 (4) ◽  
pp. 538-544
Author(s):  
Peng Sang ◽  
Jiahui Zhao ◽  
Shun Wang ◽  
Hui Yang ◽  
Huijuan Shi
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Sham Group ◽  
Akt Signaling ◽  
Sod Activity ◽  
Memory Ability ◽  
Group I ◽  
Mda Content

Objective: Studies have shown that Rehmanniae Decoction (Reh) has therapeutic effect on vascular dementia (VD). PI3K/AKT signaling regulates oxidative stress damage and cell apoptosis. Our study intends torehmanniae decoction's effect on the neural function in VD mice. Methods: The mice were divided into Sham group, VD group, low dose Reh+ VD group and high dose Reh+ VD group. Water maze test was used to assess learning and memory ability. The activity of caspase-3, the content of MDA and the activity of SOD enzyme in hippocampus were detected. In vitro , HT22 cells were divided into control group, I–R group, I–R+ 2% Reh serum, I–R+ 4% Reh serum. Flow cytometry was used to detect the intracellular content of ROS and cell apoptosis. Results: Compared with sham group, the learning and memory ability of mice in VD group was significantly decreased. p-AKT level and SOD activity in the hippocampus was decreased, the Caspase-3 activity and MDA content was significantly increased. After treatment of Reh, the learning and memory ability of VD model mice was significantly improved, p-AKT protein expression and SOD activity were up-regulated, and Caspase-3 activity and MDA content were reduced. Conclusion: Rehmanniae decoction alleviates the oxidative stress and inhibits cell apoptosis to improve the function of brain by regulating PI3K/AKT pathway.

scholarly journals Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress

2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Caspase 3 ◽  
Visual Learning ◽  
Morris Water Maze Test ◽  
High Dose ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Neural Apoptosis ◽  
The Brain

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.

scholarly journals To Evaluate the Effect of Vitamin E Therapy on the Oxidative Stress Markers (Nitric Oxide, SOD, Glutathione Peroxidase) & Vitamin E Levels in Pulmonary Tuberculosis Patients

2020 ◽  
Vol 9 (40) ◽  
pp. 2970-2975
Author(s):  
Rohit John Chaudhary ◽  
Bharti Kwatra Uppal
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vitamin E ◽  
Glutathione Peroxidase ◽  
Pulmonary Tuberculosis ◽  
Older Age ◽  
Control Group ◽  
Ros Production ◽  
Age Group ◽  
Sod Activity

BACKGROUND Severe oxidative stress has been reported in TB patients because of infection associated with malnutrition and poor immunity. Mycobacteria can induce reactive oxygen species (ROS) production by activating phagocytes, and enhanced ROS production may promote tissue injury and inflammation. We wanted to compare the effect of antioxidant administration in the outcome of ATT treatment between the test and the control group. METHODS This perspective study was conducted in the Departments of Biochemistry and Chest Medicine, CMC & Hospital. Hundred patients (fifty controls and fifty tests) who were diagnosed as pulmonary tuberculosis and started on DOT therapy under RNTCP during this period were included in the study. Each participant in the study was subjected to the following test at the first visit, 2nd month and 6th month follow up (biochemical markers Nitric oxide, SOD, Glutathione Peroxidase and Vitamin E levels). Statistical analysis was done using SPSS version. RESULTS The results were based on four categories (male / female, alcoholic / non-alcoholic, smoker / non-smoker, and younger / older age group). Females had responded better with greater fall in percentage of nitric oxide values (69 %) than males (64.1 %). The mean of SOD activity (277.5 + / - 31.5) was more in smokers than non-smokers (261.3 + / - 36.0) & percentage fall of nitric oxide in smokers (65 %) & non-smokers (67 %). In alcoholics the percentage fall of nitric oxide (68.3 %) was higher with more SOD activity (Mean 278.7 + / - 27.6) than non-alcoholics (Mean 256 + / - 38.0) indicating a positive correlation of smoking & alcoholism with tuberculosis. Younger age group responded better with more fall in the percentage of nitric oxide (67 %) & mean SOD activity (265.8 + / - 30.1) than older age group. CONCLUSIONS Antioxidant supplementation reduces oxidative stress, improves the effectiveness of ATT therapy, and thus helps in improving the outcome in pulmonary tuberculosis. KEY WORDS Pulmonary TB, ATT (Anti-Tubercular Treatment), Antioxidants & Free Radicals

Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats

2019 ◽  
Vol 37 (4) ◽  
pp. 965-976 ◽  
Author(s):  
Zhara Hakimi ◽  
Hossein Salmani ◽  
Narges Marefati ◽  
Zohre Arab ◽  
Zahra Gholamnezhad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Brain Tissue ◽  
Protective Effects ◽  
Tissue Inflammation ◽  
And Oxidative Stress

scholarly journals Structural Characterization and Antioxidant Activity of Polysaccharides from Athyrium multidentatum (Doll.) Ching in d-Galactose-Induced Aging Mice via PI3K/AKT Pathway

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3364 ◽  
Author(s):  
Liang Jing ◽  
Jing-Ru Jiang ◽  
Dong-Mei Liu ◽  
Ji-Wen Sheng ◽  
Wei-Fen Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Protein Expression ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Protective Mechanism ◽  
Related Factor ◽  
Bax Protein ◽  
Gene And Protein Expression

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. Key findings: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. Conclusion: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.

scholarly journals N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Jiying Jiang ◽  
Shuna Yu ◽  
Zhengchen Jiang ◽  
Cuihong Liang ◽  
Wenbo Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Mitochondrial Apoptosis ◽  
Sod Activity ◽  
Stress Injury ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

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