scholarly journals Administration of Momordica charantia Enhances the Neuroprotection and Reduces the Side Effects of LiCl in the Treatment of Alzheimer’s Disease

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1888 ◽  
Author(s):  
Hei-Jen Huang ◽  
Shu-Ling Chen ◽  
Yen-Ting Chang ◽  
Jong-Ho Chyuan ◽  
Hsiu Hsieh-Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Neuroprotective Effect ◽  
Combined Treatment ◽  
Momordica Charantia ◽  
Natural Food ◽  
Tau Hyperphosphorylation ◽  
Protective Effects

Recently, the use of natural food supplements to reduce the side effects of chemical compounds used for the treatment of various diseases has become popular. Lithium chloride (LiCl) has some protective effects in neurological diseases, including Alzheimer’s disease (AD). However, its toxic effects on various systems and some relevant interactions with other drugs limit its broader use in clinical practice. In this study, we investigated the in vitro and in vivo pharmacological functions of LiCl combined with Momordica charantia (MC) in the treatment of AD. The in vitro results show that the order of the neuroprotective effect is MC5, MC3, MC2, and MC5523 under hyperglycemia or tau hyperphosphorylation. Therefore, MC5523 (80 mg/kg; oral gavage) and/or LiCl (141.3 mg/kg; intraperitoneal injection) were applied to ovariectomized (OVX) 3×Tg-AD female and C57BL/6J (B6) male mice that received intracerebroventricular injections of streptozotocin (icv-STZ, 3 mg/kg) for 28 days. We found that the combined treatment not only increased the survival rate by reducing hepatotoxicity but also increased neuroprotection associated with anti-gliosis in the icv-STZ OVX 3×Tg-AD mice. Furthermore, the cotreatment with MC5523 and LiCl prevented memory deficits associated with reduced neuronal loss, gliosis, oligomeric Aβ level, and tau hyperphosphorylation and increased the expression levels of synaptic-related protein and pS9-GSK3β (inactive form) in the icv-STZ B6 mice. Therefore, MC5523 combined with LiCl could be a potential strategy for the treatment of AD.

Escitalopram Alleviates Alzheimer’s Disease-Type Tau Pathologies in the Aged P301L Tau Transgenic Mice

2020 ◽  
Vol 77 (2) ◽  
pp. 807-819
Author(s):  
Yan-Juan Wang ◽  
Wei-Gang Gong ◽  
Qing-Guo Ren ◽  
Zhi-Jun Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Phosphorylation ◽  
Tau Hyperphosphorylation ◽  
Protective Effects ◽  
Protein Levels ◽  
Phosphorylated Akt ◽  
Biochemical Analyses ◽  
Gsk 3Β

Background: The inhibition of tau hyperphosphorylation is one of the most promising therapeutic targets for the development of Alzheimer’s disease (AD) modifying drugs. Escitalopram, a kind of selective serotonin reuptake inhibitor antidepressant, has been previously reported to ameliorate tau hyperphosphorylation in vitro. Objective: In this study, we determined whether escitalopram alleviates tau pathologies in the aged P301L mouse. Methods: Mice were intraperitoneal injected with either escitalopram or saline for 4 weeks, and a battery of behavioral tests were conducted before tissue collection and biochemical analyses of brain tissue with western blot and immunohistochemistry. Results: Wild-type (Wt) mice statistically outperformed the aged pR5 mice in the Morris water maze, while escitalopram treatment did not significantly rescue learning and memory deficits of aged pR5 mice. Tau phosphorylation at different phosphorylation sites were enhanced in the hippocampus of aged pR5 mice, while escitalopram treatment significantly decreased tau phosphorylation. The levels of phosphorylated GSK-3β and phosphorylated Akt were significantly decreased in the hippocampus of aged pR5 mice, while escitalopram administration markedly increased the expression level. The aged pR5 mice showed significant decreases in PSD95 and PSD93, while the administration of escitalopram significantly increased PSD95 and PSD93 to levels comparable with the Wt mice. Conclusion: The protective effects of escitalopram exposure during advanced AD are mainly associated with significant decrease in tau hyperphosphorylation, increased numbers of neurons, and increased synaptic protein levels, which may via activation of the Akt/GSK-3β signaling pathway.

scholarly journals Protection Induced By Ginsenoside Rb1 in Alzheimer’s Disease Model is Associated With Redressing The Neuronal Hyperexcitability Which is Regulated By Nav1.2 and Nav1.6

2021 ◽  
Author(s):  
shan li ◽  
Min-Nan Lu ◽  
Qian Wang ◽  
Yun Yuan ◽  
Xiao-Min Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Potential Candidate ◽  
Protective Effects ◽  
Ginsenoside Rb1 ◽  
Patch Clamp Recording

Abstract Background: Alzheimer’s disease (AD), a neurodegenerative disease showing multiple complex pathomechanism alterations, has affected the normal life of many old people. It is urgent to find an effective medicine for AD. Ginsenoside Rb1 (Rb1) is the main component of panax notoginseng saponins, a famous Chinese herbal medicine, and is expected to be a useful drug in the treatment of AD. This study mainly explored the potential effects of Rb1 in model of AD in vivo and in vitro, and investigated the possible mechanisms. Materials and methods: We studied the neuroprotective effect of Rb1 in transgenic mouse animal model and cell AD model in vitro. The cognitive function of APP/PS1 mice was measured in Morris water maze and Novel Object Recognition. Electrophysiological patch clamp recording and electrophysiology were used to nerve excitability. Further, the expression of proteins of Nav1.2 and Nav1.6 were used by Western blot. Results: We found that Rb1 treatment significantly improved the cognitive and memory loss, and reversed the hyperexcitability by altering the expressions of Nav1.2 and Nav1.6 of APP/PS1 mice. Further, Rb1 improved the hyperexcitability induced by Aβ1-42-injured neurons, which might be associated with alteration of the expressions of Nav1.2 and Nav1.6. As we expect, Rb1 attenuated Aβ1-42-induced injury in primary neurons. Conclusion: Our data showed that Rb1 played a critical role in improvement of the cognitive deficit and abnormal excitability of AD by regulating Nav1.2 and Nav1.6 expressions. Thus, Rb1 shows protective effects on AD models and may be a potential candidate for AD treatment.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

Targeting Tau Hyperphosphorylation via Kinase Inhibition: Strategy to Address Alzheimer's Disease

2020 ◽  
Vol 20 (12) ◽  
pp. 1059-1073 ◽  
Author(s):  
Ahmad Abu Turab Naqvi ◽  
Gulam Mustafa Hasan ◽  
Md. Imtaiyaz Hassan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Glycogen Synthase ◽  
Paired Helical Filaments ◽  
Tau Hyperphosphorylation ◽  
Microtubule Stabilization ◽  
Extracellular Signal

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.

scholarly journals Network Pharmacology-Based Study of the Underlying Mechanisms of Huangqi Sijunzi Decoction for Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wei Zhang ◽  
Mingti Lv ◽  
Yating Shi ◽  
Yonghui Mu ◽  
Zhaoyang Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Network Pharmacology ◽  
Neuroprotective Effects ◽  
Target Network ◽  
Compound Target

Background. Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer’s disease (AD). Methods. The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. Results. Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. Conclusion. HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

Design and Synthesis of Novel Aminoalkanamides Targeting Neurodegeneration and Symptoms of Alzheimer’s Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Agnieszka Jankowska ◽  
Grzegorz Satała ◽  
Gniewomir Latacz ◽  
Anna Partyka ◽  
Annamaria Lubelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Neuroprotective Effect ◽  
Antidepressant Activity ◽  
Receptor Affinity ◽  
Design And Synthesis ◽  
Novel Drugs ◽  
Adme Properties

Background: There is currently no drug that slows the process of neurodegeneration or alleviates the cognitive and depressive symptoms in patients with Alzheimer’s disease. Due to the increasing number of Alzheimer’s patients, there is an urgent need to develop novel drugs with neuroprotective, procognitive, and antidepressant properties. Objective: The aim of this study was to design, synthesize, and evaluate novel aminoalkanamides with serotonin 5-HT1A/5-HT7 receptor affinity and phosphodiesterase (PDE) inhibitory activity as a new approach to combat neurodegeneration and symptoms of Alzheimer’s disease. Methods: The newly designed compounds were synthesized using classical methods of organic chemistry and tested in vitro for their receptor affinity, functional profile, enzyme inhibition, and ADME properties. The neuroprotective effect against H2O2-induced increase of reactive oxygen species level was tested in SH-SY5Y cells. The novel object recognition and forced swimming tests were used to evaluate the procognitive and antidepressant activity, respectively. Results: Synthesized aminoalkanamides were characterized as potent 5-HT1A receptor antagonists with additional 5-HT7 receptor antagonistic properties and PDE4B inhibitory activity. Selected compound 15 showed neuroprotective, procognitive, and antidepressant properties. In addition, compound 15 revealed suitable ADME properties expressed as a good membrane permeability and a high metabolic stability. Conclusion: This study revealed a new class of compounds that may be useful in the search for an effective drug in the alleviation of neurodegeneration and symptoms of Alzheimer’s disease.

scholarly journals Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kexin Wang ◽  
Hongyan Li ◽  
Hongxing Wang ◽  
Jun-hui Wang ◽  
Feng Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Conditioned Medium ◽  
Hippocampal Neurons ◽  
Cell Damage ◽  
Future Application ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Amyloid Toxicity

Neurons suffer detrimental effects from β-amyloid toxicity in Alzheimer’s disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons against the Aβ-induced cell toxicity so far. In the present study, we investigated whether irisin could protect neurons against Aβ- (25–35) induced cell damage and explored the possible underlying mechanisms. Primary cell cultures of astrocytes and neurons were established. Conditioned medium from astrocyte was collected for the treatment and biochemistry assay study. To explore the protein expression changes, Western blot and ELISA assays were used in these in vitro cell culture models. Exposure of hippocampal neurons to 10 μM Aβ (25–35) caused significant reduction on cell viability, and the toxic effect was not significantly reduced by the coadministration of irisin. However, pretreated astrocyte-conditioned medium with irisin for 12 hours notably protected the neurons from the toxicity of Aβ. Also, we found that irisin could attenuate the release of IL-6 and IL-1β from cultured astrocytes and decrease the expression level of COX-2 and phosphorylation of AKT. Last, we found that irisin could reduce NFκB activation in astrocyte exposed to Aβ by preventing the phosphorylation and the loss of IκBα. Our finding may provide novel evidence for the future application of irisin in the treatment of Alzheimer’s disease and the memory dysfunction in diabetes mellitus.

Neuroprotective effect of the hexapeptide HLDF-6 on rat hippocampal neurons on the in vivo and in vitro models of alzheimer’s disease

2006 ◽  
Vol 32 (4) ◽  
pp. 360-367 ◽  
Author(s):  
I. A. Kostanyan ◽  
S. S. Zhokhov ◽  
Z. I. Storozheva ◽  
A. T. Proshin ◽  
E. A. Surina ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
In Vitro Models

scholarly journals Resveratrol and Neuroprotection: Impact and Its Therapeutic Potential in Alzheimer's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Md. Habibur Rahman ◽  
Rokeya Akter ◽  
Tanima Bhattacharya ◽  
Mohamed M. Abdel-Daim ◽  
Saad Alkahtani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Tau Proteins ◽  
Amyloid Peptides ◽  
Work Done

Alzheimer’s disease (AD) is a progressive cortex and hippocampal neurodegenerative disease which ultimately causes cognitively impaired decline in patients. The AD pathogen is a very complex process, including aggregation of Aβ (β-amyloid peptides), phosphorylation of tau-proteins, and chronic inflammation. Exactly, resveratrol, a polyphenol present in red wine, and many plants are indicated to show the neuroprotective effect on mechanisms mostly above. Resveratrol plays an important role in promotion of non-amyloidogenic cleavage of the amyloid precursor protein. It also enhances the clearance of amyloid beta-peptides and reduces the damage of neurons. Most experimental research on AD and resveratrol has been performed in many species, both in vitro and in vivo, during the last few years. Nevertheless, resveratrol’s effects are restricted by its bioavailability in the reservoir. Therefore, scientists have tried to improve its efficiency by using different methods. This review focuses on recent work done on the cell and animal cultures and also focuses on the neuroprotective molecular mechanisms of resveratrol. It also discusses about the therapeutic potential onto the treatment of AD.

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