Rosuvastatin Calcium Affects Alzheimer's Disease Through Regulating Defensive Transduction Pathways of Oxidative and Chemical Stress Signaling Pathway

2019 ◽  
Vol 9 (10) ◽  
pp. 1414-1419
Author(s):  
Zhongjin Liu ◽  
Ruiqing Li ◽  
Chunmei Zhang ◽  
Jia Liu ◽  
Haiyan Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Ability ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Sham Operation ◽  
Sod Activity ◽  
Sham Operation Group ◽  
Operation Group ◽  
Rosuvastatin Calcium

Alzheimer's disease (AD) treatment is not effective. Statins are lipid-lowering drugs. However, the role and mechanism of statins for treating AD remains unclear. SD rats were separated into sham operation group; AD group and rosuvastatin calcium group followed by analysis of cognitive function and neuronal morphology. ELISA was to measure the level of TNF-α and IL-1; SOD activity and ROS levels were measured,. Real-time quantitative PCR was to analyze Bcl-2 and Bax level. The expression of Nuclear Erythroid 2-Related Factor 2/Antioxidant Responsive Element (NRF2/ARE) signaling pathway was analyzed by Western blot. Compared with sham operation group, the cognitive ability of the AD group was significantly decreased; with elevated secretion of TNF-α and IL-1, decreased SOD activity, increased ROS generation, decreased Bcl-2 expression as well as increased Bax expression (P < 0.05). In addition, AD group rats showed neuronal damage in the hippocampus and decreased expression of NRF2 and ARE. However, rosuvastatin calcium treatment improved cognitive ability, decreased TNF-α and IL-1 secretion, increased SOD activity, decreased ROS content, increased Bcl-2 expression and decreased Bax expression as well as ameliorated neuronal damage, increased number of nerve cells, and increased expression of NRF2 and ARE. Rosuvastatin calcium can inhibit the oxidative stress and inflammation, inhibit the apoptosis of hippocampus cells and improve the cognitive ability of AD rats by regulating NRF2/ARE signaling pathway.

scholarly journals Oleanolic Acid Ameliorates Aβ25-35 Injection-induced Memory Deficit in Alzheimer’s Disease Model Rats by Maintaining Synaptic Plasticity

2018 ◽  
Vol 17 (5) ◽  
pp. 389-399 ◽  
Author(s):  
Kai Wang ◽  
Weiming Sun ◽  
Linlin Zhang ◽  
Wei Guo ◽  
Jiachun Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Oleanolic Acid ◽  
Memory Deficit ◽  
Sham Operation ◽  
Group Model ◽  
Model Group ◽  
Sham Operation Group ◽  
Operation Group

Background: Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer’s disease (AD). Objective: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. Methods: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured. Results: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group. Conclusion: The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.

scholarly journals Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice

2020 ◽  
Vol 14 ◽  
Author(s):  
Anping Xu ◽  
Qingtao Zeng ◽  
Yinshan Tang ◽  
Xin Wang ◽  
Xiaochen Yuan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Cognitive Ability ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Disease Model ◽  
Tau Phosphorylation ◽  
Downstream Target ◽  
Abnormal Glucose Metabolism

BackgroundAlzheimer’s disease (AD) is mainly manifested as a continuous and progressive decline in cognitive ability. Neurofibrillary tangles (NFTs) are pathological hallmarks of AD and due to accumulated phosphorylated Tau. Glycogen synthase kinase-3β (GSK3β), as a major Tau kinase and a downstream target of the serine protein kinase B (AKT) signaling pathway, can regulate Tau phosphorylation in AD. Importantly, the AKT/GSK3β signaling pathway is involved in glucose metabolism, and abnormal glucose metabolism is found in the AD brain. Numerous studies have shown that electroacupuncture (EA), which is thought to be a potential complementary therapeutic approach for AD, can protect cognitive ability to a certain extent.ObjectiveThe purpose of this experiment was to investigate whether the protective and beneficial mechanism of EA on cognition was mediated by the AKT/GSK3β signaling pathway, thereby improving glucose metabolism and Tau phosphorylation in the brain.MethodsEA was applied to the Baihui (GV20) and Yintang (GV29) acupoints of 6-month-old amyloid precursor protein (APP)/presenilin-1 (PS1) mice for 20 min, and then quickly prick Shuigou (GV26) acupoint. The intervention was performed once every other day for 28 days. The Morris water maze (MWM) test was performed on C57BL/6N (Non-Tg) mice, APP/PS1 (Tg) mice and EA-treated Tg (Tg + EA) mice to evaluate the effect of EA therapy on cognitive function. 18F-FDG positron emission tomography (PET), immunohistochemistry, and western blotting (WB) were used to investigate the possible mechanism underlying the effect of EA on AD.ResultsEA treatment significantly improved the cognition of APP/PS1 mice and the glucose uptake rate in the hippocampus. Furthermore, EA inhibited the phosphorylation of Tau (Ser199 and Ser202) proteins by inducing AKT (Ser473) and GSK3β (Ser9) phosphorylation.ConclusionThese results demonstrate that EA intervention protects cognition by enhancing glucose metabolism and inhibiting abnormal phosphorylation of Tau protein in the AD model mice, and the AKT/GSK3β pathway might play an irreplaceable role in the regulation process.

scholarly journals Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nanhui Yu ◽  
Yongpan Huang ◽  
Yu Jiang ◽  
Lianhong Zou ◽  
Xiehong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Tunel Staining ◽  
Ganoderma Lucidum Triterpenoids

Alzheimer’s disease (AD) is the most common cause of dementia among senior citizen. Ganoderma lucidum triterpenoids (GLTs) have nutritional health benefits and has been shown to promote health and longevity, but a protective effect of GLTs on AD damage has not yet been reported. The objective of this research was to elucidate the phylactic effect of GLTs on AD model mice and cells and to explore its underlying mechanisms. Morris water maze (MWM) test was conducted to detect changes in the cognitive function of mice. Hematoxylin-eosin (HE) staining was applied to observe pathological changes in the hippocampus. Silver nitrate staining was applied to observe the hippocampal neuronal tangles (NFTs). Apoptosis of the hippocampal neurons in mouse brain tissue was determined by TUNEL staining. The expression levels of apoptosis-related protein Bcl2, Bax, and caspase 3/cleaved caspase 3; antioxidative protein Nrf2, NQO1, and HO1; and ROCK signaling pathway-associated proteins ROCK2 and ROCK1 were measured by western blot. In vivo experiments show that 5-month-old APP/PS1 mice appeared to have impaired acquisition of spatial learning and GLTs could reduce cognitive impairment in AD mice. Compared to normal mice, the hippocampus of APP/PS1 mouse’s brains was severely damaged, while GLTs could alleviate this symptom by inhibiting apoptosis, relieving oxidative damage, and inactivating the ROCK signaling pathway. In in vitro cell experiments, Aβ25-35 was applied to induce hippocampal neurons into AD model cells. GLTs promoted cell proliferation, facilitated superoxide dismutase (SOD) expression, and inhibited malondialdehyde (MDA) and lactic dehydrogenase (LDH) expression of neurons. Our study highlights that GLTs improve cognitive impairment, alleviate neuronal damage, and inhibit apoptosis in the hippocampus tissues and cells in AD through inhibiting the ROCK signaling pathway.

Effects of Shikonin on the Bone Microenvironment and Heterogeneity of Spinal Tumor Cells by Regulating the High Mobility Group Protein B1-Toll Like Receptor 4-Nuclear Factor Kappa-B Signaling Pathway

2019 ◽  
Vol 9 (11) ◽  
pp. 1595-1599
Author(s):  
Bo Chen ◽  
Bo Liu ◽  
Feng-Feng Nie ◽  
Zai-Qing Zhang ◽  
Fa-Qing Wan
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Spinal Tumor ◽  
Spinal Tumors ◽  
Sham Operation ◽  
Bone Microenvironment ◽  
Model Group ◽  
Sham Operation Group ◽  
Tlr4 Mrna ◽  
Operation Group

Aim: The present study was conducted with an attempt to evaluate the potential therapeutic effect of shikonin on spinal tumors in vivo and its mechanism. Methods: The morphology of rat spinal tumor was observed by H&E staining, and apoptosis of rat spinal tumor was detected by transfection method and TUNEL method. In addition, the expression of cytokine mRNA and related proteins in spinal tumors of rats were detected by real-time PCR and Western blotting assays. Results: At the same period, the BBB score in the model group was significantly lower than that in the sham operation group and the shikonin group (P < 0.05). Compared with the sham operation group, the BBB score in the shikonin group was significantly lower than that in the sham operation group (P < 0.05), but significantly higher than that in the model group (P < 0.05). Based on the RT-PCR results, the level of HMGB1 mRNA in the shikonin group was significantly lower than that of the model group (P < 0.05), and the level of TLR4 mRNA in the model group was significantly lower than that in the model group (P < 0.05). Moreover, the NF-κB mRNA level in the shikonin group was significantly lower than that in the model group (P < 0.05). The expression level of HMGB1, TLR4 and NF- B in the shikonin group was significantly lower than that in the model group (P < 0.05). Together, the results revealed that shikonin reduced the expression of HMGB1, TLR4 and NF-κB mRNA and protein. The apoptosis rate of tumor cells in the shikonin group was significantly higher than that in the model group (P < 0.05). The expression of caspase-3 in the shikonin group was significantly higher than that in the model group, which further indicated that shikonin could promote apoptosis of spinal tumor cells in rats. Conclusion : Shikonin has the potential to affect the heterogeneity of the bone microenvironment and spinal tumor cells by regulating the HMGB1-TLR4-NF-κB signaling pathway.

scholarly journals Effects of Aspirin on Myocardial Ischemia-Reperfusion Injury in Rats through STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Zhenjun Wu ◽  
Xuewen Li ◽  
Xiuyue Li ◽  
Lihua Yu
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sham Operation ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Stat3 Signaling Pathway ◽  
Operation Group ◽  
Myocardial Ischemia Reperfusion ◽  
Aspirin Group

Objective. To investigate the role and mechanism of aspirin in myocardial injury induced by myocardial ischemia-reperfusion in rats through STAT3 signaling pathway. Methods. Sixty rats were randomly divided into three groups: the sham operation group, MI/R group, and MI/R+aspirin group (aspirin group). The rats in the sham operation group did not ligate the LAD coronary artery, while the aspirin group ligated the LAD coronary artery, which caused the suture to be loosened after 30 minutes ischemia, and 60 mg/kg aspirin was injected into the tail vein 10 minutes before reperfusion. After three hours of reperfusion, the ultrasound system was used to collect hemodynamic parameters, including ejection fraction (EF%), shortening fraction (FS%), and left ventricular end-systolic pressure (LVESP%) and left ventricular end-diastolic pressure (LVEDP%). Finally, the rats were euthanized; then, blood samples were taken for biochemical examination, myocardial tissue was collected, and the left ventricle was used for subsequent experiments. The gene expression levels of Bax and Bcl-2 were detected by PCR. The protein expression levels of Bcl-2, Bax, p-JAK2, total JAK2, p-STAT3, and total STAT3 were detected by Western blot. Results. Compared with the sham operation group and the aspirin group, the area of myocardial infarction in the MI/R was significantly increased ( p < 0.05 ). In terms of hemodynamic parameters, LVEDP was significantly elevated in the MI/R group. The results of PCR showed that compared with the MI/R group, the mRNA expression of Bax in the aspirin group was significantly decreased, while that of Bcl-2 was significantly increased ( p < 0.05 ). Western blot analysis showed that compared with the MI/R group, aspirin pretreatment significantly increased the expression levels of p-STAT3 and p-JAK2 ( p < 0.05 ). Conclusion. The mechanism of aspirin preconditioning to protect the heart from MI/R injury appears to be related to JAK2/STAT3 and related to the activation of the signaling pathway.

scholarly journals In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

2021 ◽  
Vol 22 (9) ◽  
pp. 4818
Author(s):  
Annica Pröhl ◽  
Milijana Batinic ◽  
Said Alkildani ◽  
Michael Hahn ◽  
Milena Radenkovic ◽  
...  
Keyword(s):  
Bone Substitute ◽  
Sham Operation ◽  
Bone Substitute Material ◽  
Water Binding ◽  
Sham Operation Group ◽  
Operation Group ◽  
Substitute Material ◽  
Tissue Reactions ◽  
Inflammatory Tissue

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.

Assessment of the therapeutic potential of hesperidin and proteomic resolution of diabetes-mediated neuronal fluctuations expediting Alzheimer’s disease

RSC Advances ◽  
2015 ◽  
Vol 5 (58) ◽  
pp. 46965-46980 ◽  
Author(s):  
Sapna Khowal ◽  
Malik M. A. Mustufa ◽  
Naveen K. Chaudhary ◽  
Samar Husain Naqvi ◽  
Suhel Parvez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Early Stage ◽  
Type Iii

Alzheimer’s disease (AD) has been proposed as type III diabetes mellitus. Prognosis and early stage diagnosis of AD is essentially required in diabetes to avoid extensive irreversible neuronal damage.

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