scholarly journals Prophylactic Use of Troxerutin Can Delay the Development of Diabetic Cognitive Dysfunction and Improve the Expression of Nrf2 in the Hippocampus on STZ Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Songyun Zhang ◽  
Lingling Yuan ◽  
Lihui Zhang ◽  
Caige Li ◽  
Jie Li

Background. With the change in lifestyle and the aging population, the incidence of cognitive dysfunction in diabetes mellitus is rising sharply. Oxidative stress is an important mechanism in the development of diabetic cognitive dysfunction. Nuclear factor E2-related factor 2 (Nrf2) is the core transcription factor of antioxidative stress. Early prevention and treatment of diabetic cognitive dysfunction can reduce the incidence of dementia and improve the quality of life of diabetic patients. Aim. This study was aimed at determining effect of troxerutin on the development of cognitive dysfunction and the expression level of Nrf2 in the hippocampus of streptozotocin (STZ) diabetic rats, when used in the early preventive stage. Methods. An STZ-induced diabetic rat model was established (n=30), and the animals were randomly divided into 2 groups: diabetic control group (DC, n=15) and diabetic troxerutin intervention group (DT, n=15). Another 10 normoglycemic rats were put into a normal control group (NC, n=10). While the DT group was injected with troxerutin (60 mg/kg), the DC group and the NC group were injected with physiological saline for 12 weeks daily. Learning and memory behaviors were tested using the Morris water maze test. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, mRNA level, and protein level of Nrf2 were measured. Data were collected and analyzed by the statistical software package SPSS 19.0, which included one-way analysis of variance with completely randomized design. Results. Learning and memory levels were significantly improved in the DT group compared with the DC group. Moreover, in the DT group, the expression level of Nrf2 in the hippocampus was increased, activity of SOD was elevated, and MDA content was decreased. Conclusion. Prophylactic use of troxerutin delays the development of diabetic cognitive dysfunction and increases the expression level of Nrf2 in the hippocampus of STZ diabetic rats.

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


2021 ◽  
pp. 1-9
Author(s):  
Guizhen Liu ◽  
Yuchuan Sun ◽  
Fei Liu

<b><i>Objective:</i></b> The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. <b><i>Methods:</i></b> Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. <b><i>Results:</i></b> Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. <b><i>Conclusion:</i></b> Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Gil-Yong Lee ◽  
Chan Lee ◽  
Gyu Hwan Park ◽  
Jung-Hee Jang

Increasing evidence suggests that neurodegenerative disorders such as Alzheimer’s disease (AD) are mediated via disruption of cholinergic neurons and enhanced oxidative stress. Therefore, attention has been focused on searching for antioxidant phytochemicals for the prevention and/or treatment of AD through their ability to fortify cholinergic function and antioxidant defense capacity. In this study, we have investigated the neuroprotective effect ofα-pinene (APN) against learning and memory impairment induced by scopolamine (SCO, 1 mg/kg, i.p.), a muscarinic receptor antagonist in C57BL/6 mice. Administration of APN (10 mg/kg, i.p.) significantly improved SCO-induced cognitive dysfunction as assessed by Y-maze and passive avoidance tests. In Morris water-maze test, APN effectively shortened the mean escape latency to find the hidden platform during training days. To further elucidate the molecular mechanisms underlying the neuroprotective effect of APN, the expression of proteins involved in the acetylcholine metabolism and antioxidant system was examined. Particularly, APN treatment increased mRNA expression of choline acetyltransferase in the cortex and protein levels of antioxidant enzymes such as heme oxygenase-1 and manganese superoxide dismutase in the hippocampus via activation of NF-E2-related factor 2. These findings suggest the possible neuroprotective potentials of APN for the management of dementia with learning and memory loss.


2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.


2018 ◽  
Vol 8 (1) ◽  
pp. 6-6 ◽  
Author(s):  
Parisa Jamor ◽  
Hassan Ahmadvand ◽  
Hesam Ashoory ◽  
Esmaeel Babaeenezhad

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.


2020 ◽  
Vol 12 (10) ◽  
pp. 1215-1220
Author(s):  
Bingshuang Xue ◽  
Yi Xue ◽  
Jiaojiao Zhou ◽  
Qichao Yang

The occurrence of complications of diabetic patients not only increases the difficulty and burden of treatment but also significantly affects the health and safety of patients. Traditional therapeutic drugs are prone to drug resistance, which affects the therapeutic effect. In recent years, the application of plant-derived natural compounds in the treatment of diseases has become a hot spot in the research of diabetes drugs. Curcumin has anti-tumor, anti-inflammation, anti-oxidation and antimicrobial effects, but the mechanism of its effect on cardiomyocytes in diabetic patients is not yet clear. In this study, curcumin was prepared into nano-preparations and its mechanism of action in the process of myocardial fibrosis in diabetic rats was further explored. We found that injection of curcumin nano-suspension can increase the LVIDd and LVFS of rats, while reducing the serum CKMB, LDH, AST and cTnI levels. Further exploration found that curcumin can reduce serum TNF- α and IL-1 β levels in diabetic rats, while increasing the SOD and GSH-Px activities of myocardial tissue, and reducing MDA content. These suggests that curcumin can reduce inflammation and oxidative stress in diabetic rats. Therefore, this study believes that curcumin nano-suspension can effectively inhibit diabetic cardiomyocyte fibrosis, oxidative stress, and inflammation and protect the rat myocardium.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Peng Ren ◽  
Jingwei Chen ◽  
Bingxuan Li ◽  
Mengzhou Zhang ◽  
Bei Yang ◽  
...  

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.


2011 ◽  
Vol 26 (S2) ◽  
pp. 503-503
Author(s):  
R. Wang

ObjectiveTo investigate the effect of Analog P165 of APP5-mer peptide on change of learning and memory ability in type 3 diabetes rats.MethodHealthy adult male rats were randomly divided into 3 groups: Control group; type 3 diabetes (T3DM) group; T3DM administrated P165 group. T3DM models were induced by intracerebroventricular injection of Streptozotocin (STZ, 3 mg/kg) bilaterally. P165 groups were treated with gastric P165 (355 μg/kg) Then, learning and memory ability was detected by Morris water maze test. Body weight and serum glucose were recorded. The rat serum Insulin, Gluocagon, insulin-like growth factor-1 (IFG-1) was detected by ELISA method.ResultsIn the Morris water maze test, compared with control group, the escape latency increased significantly (p < 0.05) in model group at the 3rd day. Compared with model group, the escape latency decreased significantly (p < 0.05) in the models administrated P165 group at the 3rd day. Although there was no significant difference, the escape latency decreased in P165 group at the 4th and 5th day. From the result of rats blood serum detection, the serum IGF-1 level decreased significantly in the model group (p < 0.01) than the control group. The serum IGF-1 level increased significantly in P165 treated group(p < 0.05).The body weight and the serum glucose, insulin, gluocagon had no significant difference among the groups in the period of experiment.ConclusionThere is learning and memory impairment in the T3DM rats. P165 can raise the rats blood serum IGF-1 level, ameliorate learning and memory ability but don’t influence the serum glucose.


Author(s):  
Fatemeh Soleymanzadeh ◽  
Minoo Mahmoodi ◽  
Siamak Shahidi

Objective: Diabetes mellitus is recognized as one of the serious global health problems. There are evidences regarding the high prevalence of sexual dysfunction in diabetic patients. Experimental studies revealed a positive effect of Vitex agnus-castus (Vitex), on sexual function and behaviors. In this research, the effect of Vitex on sexual hormones in streptozotocin-(STZ) induced diabetic rats was investigated. Materials and methods: A Thirty adult female Wistar rats were divided into five groups. 1-control group (non-diabetic), 2- diabetic group (received normal saline) and three induced diabetic groups treated with different doses (400, 200 and 100 mg/kg) of Vitex. Treatment groups received Vitex fruit extract by gavage for 7 days. The levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estrogen in serum were measured. Results: Levels of LH, FSH, estrogen and progesterone and average body weight was lower in diabetic group compared to control group (p <0.010). Animals received high dose of Vitex fruit extract (400mg/kg) had significantly higher levels of serum LH, FSH, estrogen and progesterone compared to diabetic group (p < 0.010). In animals receiving minimum dose (100mg/kg) of Vitex, no difference was observed compared to diabetic group (p > 0.010). Conclusion: It can be concluded that Vitex fruit extract probably has regulatory effect on diabetes-induced change in the levels of sex hormones in female rats. Vitex fruit extract can improve serum levels of sex hormones in an animal model of STZ-induced diabetes.


2020 ◽  
Vol 77 (2) ◽  
pp. 629-640
Author(s):  
Li Hu ◽  
Shaoping Zhu ◽  
Xiaoping Peng ◽  
Kanglan Li ◽  
Wanjuan Peng ◽  
...  

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.


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