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  1. Fulltext Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system
    Fong Yen W, Basri M, Ahmad M, Ismail M
    ScientificWorldJournal, 2015;2015:495271.
    PMID: 25853145 DOI: 10.1155/2015/495271
    Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  2. sFRP-mediated Wnt sequestration as a potential therapeutic target for Alzheimer's disease
    Warrier S, Marimuthu R, Sekhar S, Bhuvanalakshmi G, Arfuso F, Das AK, et al.
    Int J Biochem Cell Biol, 2016 06;75:104-11.
    PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002
    The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  3. Fulltext Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion
    Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z
    Sci Rep, 2019 10 10;9(1):14507.
    PMID: 31601902 DOI: 10.1038/s41598-019-50954-y
    Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  4. Fulltext Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer's Disease In Vitro Model
    Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Jaafar F, et al.
    Sci Rep, 2020 06 02;10(1):8962.
    PMID: 32488024 DOI: 10.1038/s41598-020-65570-4
    Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer's disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (Aβ) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of Aβ. Mitochondrial function was shown to be affected by the increased level of Aβ and may induce cell death. Here, we aimed to compare the effects of ATF and GTF on their ability to reduce Aβ level, modulate mitochondrial function and reduce the apoptosis marker in SH-SY5Y cells stably transfected with the wild-type or mutant form of the APP gene. The Aβ level was measured by ELISA, the mitochondrial ROS and ATP level were quantified by fluorescence and luciferase assay respectively whereas the complex V enzyme activity was measured by spectrophotometry. The expressions of genes involved in the regulation of mitochondrial membrane permeability such as voltage dependent anion channel (VDAC1), adenine nucleotide translocase (ANT), and cyclophilin D (CYPD) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while the expressions of cyclophilin D (CypD), cytochrome c, Bcl2 associated X (BAX), B cell lymphoma-2 (Bcl-2), and pro-caspase-3 were determined by western blot. Our results showed that mitochondrial ROS level was elevated accompanied by decreased ATP level and complex V enzyme activity in SH-SY5Y cells expressing the mutant APP gene (p 
    Matched MeSH terms: Alzheimer Disease/drug therapy
  5. Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico
    Das S, Laskar MA, Sarker SD, Choudhury MD, Choudhury PR, Mitra A, et al.
    Phytochem Anal, 2017 Jul;28(4):324-331.
    PMID: 28168765 DOI: 10.1002/pca.2679
    INTRODUCTION: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease.

    OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.

    METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.

    RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.

    CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.

    Matched MeSH terms: Alzheimer Disease/drug therapy*
  6. Type 3 diabetes (Alzheimer's disease): new insight for promising therapeutic avenues
    Candasamy M, Mohamed Elhassan SA, Kumar Bhattamisra S, Hua WY, Sern LM, Binti Busthamin NA, et al.
    Panminerva Med, 2020 Sep;62(3):155-163.
    PMID: 32208408 DOI: 10.23736/S0031-0808.20.03879-3
    Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) are two of the most commonly occurring diseases worldwide, especially among the elderly population. In particular, the increased prevalence of AD has imposed tremendous psychological and financial burdens on society. Growing evidence suggests both AD and T2D share many similar pathological traits. AD is characterized as a metabolic disorder whereby the glucose metabolism in the brain is impaired. This closely resembles the state of insulin resistance in T2D. Insulin resistance of the brain has been heavily implicated two prominent pathological features of AD, Aβ plaques and neurofibrillary tangles. Brain insulin resistance is known to elicit a positive feed-forward loop towards the formation of AD pathology in which they affect each other in a synergistic manner. Other physiological traits shared between the two diseases include inflammation, oxidative stress and autophagic dysfunction, which are also closely associated with brain insulin resistance. In this review and depending on these underlying pathways that link these two diseases, we have discussed the potential therapeutic implications of AD. By expanding our knowledge of the overlapping pathophysiology involved, we hope to provide scientific basis to the discovery of novel therapeutic strategies to improve the clinical outcomes of AD in terms of diagnosis and treatment.
    Matched MeSH terms: Alzheimer Disease/drug therapy
  7. Synthesis of some new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides as possible therapeutic agents for Alzheimer's disease and Type-2 Diabetes
    Abbasi MA, Rehman A, Siddiqui SZ, Hadi N, Mumtaz A, Shah SAA, et al.
    Pak J Pharm Sci, 2019 Jan;32(1):61-68.
    PMID: 30772791
    In the current research work, a series of new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine (1) with 4-chlorobenzenesulfonyl chloride (2) to yield N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamide (3) which was further reacted with different alkyl/aralkyl halides (4a-n) to afford the target compounds (5a-n). Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5j) and N-(1-butyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5d), exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25±0.11 μM and 58.13±0.15 μM respectively, whereas, compounds N-benzyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5i) and N-(pentane-2-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5f) showed moderate inhibition against α-glucosidase enzyme as evident from IC50 values 74.52±0.07 and 83.52±0.08 μM respectively, relative to standards Eserine having IC50 value of 0.04±0.0001 μM for cholinesterases and Acarbose having IC50 value 38.25±0.12 μM for α-glucosidase, respectively.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  8. Non-polyphenolic compounds of a specific kind of dried grape (Maviz) inhibit memory impairments induced by beta-amyloid peptide
    Bakhtiyari E, Ahmadian-Attari MM, Salehi P, Khallaghi B, Dargahi L, Mohamed Z, et al.
    Nutr Neurosci, 2017 Oct;20(8):469-477.
    PMID: 27219682 DOI: 10.1080/1028415X.2016.1183986
    OBJECTIVES: Although grape has been recently the topic of many investigations, Maviz (a kind of dried one) has remained neglected. The aim of this study was to assess anti-Alzheimer activity of Maviz.

    METHODS: To reach this goal, total phenolic content (TPC) of ethanolic (Eth) and aqueous (Aq) extracts were determined and radical scavenging activity was assayed by 2,2-diphenyl-1-picrylhydrazyl. Chemical compositions of each extract were also determined via GC-Mass. Behavioral changes were studied via passive avoidance and Morris water maze in Aβ-induced model of Alzheimer's disease. Catalase (CAT) and superoxide dismutase (SOD) determination were also done on rats' hippocampus.

    RESULTS: The results showed that seed Eth extract has a high level of TPC and radical scavenging activity. However, this extract had surprisingly no effect on memory and CAT and SOD activities. In contrast, fruit Aq and Eth extracts (containing furfurals as major compounds) inhibited memory impairment (P 

    Matched MeSH terms: Alzheimer Disease/drug therapy
  9. Fulltext A Review on the Relationship between Tocotrienol and Alzheimer Disease
    Chin KY, Tay SS
    Nutrients, 2018 Jul 09;10(7).
    PMID: 29987193 DOI: 10.3390/nu10070881
    Alzheimer’s disease (AD) is plaguing the aging population worldwide due to its tremendous health care and socioeconomic burden. Current treatment of AD only offers symptomatic relief to patients. Development of agents targeting specific pathologies of AD is very slow. Tocotrienol, a member of the vitamin E family, can tackle many aspects of AD, such as oxidative stress, mitochondrial dysfunction and abnormal cholesterol synthesis. This review summarizes the current evidence on the role of tocotrienol as a neuroprotective agent. Preclinical studies showed that tocotrienol could reduce oxidative stress by acting as a free-radical scavenger and promoter of mitochondrial function and cellular repair. It also prevented glutamate-induced neurotoxicity in the cells. Human epidemiological studies showed a significant inverse relationship between tocotrienol levels and the occurrence of AD. However, there is no clinical trial to support the claim that tocotrienol can delay or prevent the onset of AD. As a conclusion, tocotrienol has the potential to be developed as an AD-preventing agent but further studies are required to validate its efficacy in humans.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  10. Fulltext The Biological Activities of Oleocanthal from a Molecular Perspective
    Pang KL, Chin KY
    Nutrients, 2018 May 06;10(5).
    PMID: 29734791 DOI: 10.3390/nu10050570
    Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies.
    Matched MeSH terms: Alzheimer Disease/drug therapy
  11. Fulltext Synthesis of Benzimidazole-Based Analogs as Anti Alzheimer's Disease Compounds and Their Molecular Docking Studies
    Adalat B, Rahim F, Taha M, Alshamrani FJ, Anouar EH, Uddin N, et al.
    Molecules, 2020 Oct 20;25(20).
    PMID: 33092223 DOI: 10.3390/molecules25204828
    We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a-j) and 13 benzimidazole-based Schiff bases 2 (a-m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a-j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a-m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  12. Fulltext Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases
    Kong YR, Tay KC, Su YX, Wong CK, Tan WN, Khaw KY
    Molecules, 2021 Jan 30;26(3).
    PMID: 33573300 DOI: 10.3390/molecules26030728
    Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  13. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease
    Bukhari SN, Jantan I
    Mini Rev Med Chem, 2015;15(13):1110-21.
    PMID: 26420724
    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  14. Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment
    Vanessa VV, Mah SH
    Mini Rev Med Chem, 2021;21(17):2507-2529.
    PMID: 33583373 DOI: 10.2174/1389557521666210212152514
    Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer's treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve cholinergic postsynaptic transmission. This review highlights a class of heterocycles, namely xanthone, and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano, and glycosylated xanthones, exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine, and morpholine have shown greater acetylcholinesterase inhibition activities. The structure-activity relationship of xanthones revealed that the type and position of the substituent(s) attached to the xanthone moiety influenced acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing to the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies, including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  15. Recent advances in tau-directed immunotherapy against Alzheimer's disease: an overview of pre-clinical and clinical development
    Ng PY, Chang IS, Koh RY, Chye SM
    Metab Brain Dis, 2020 10;35(7):1049-1066.
    PMID: 32632666 DOI: 10.1007/s11011-020-00591-6
    Alzheimer's disease (AD) has been a worldwide concern for many years now. This is due to the fact that AD is an irreversible and progressive neurodegenerative disease that affects quality of life. Failure of some Phase II/III clinical trials in AD targeting accumulation of β-amyloid in the brain has led to an increase in interest in studying alternative treatments against tubulin-associated unit (Tau) pathology. These alternative treatments include active and passive immunisation. Based on numerous studies, Tau is reported as a potential immunotherapeutic target for tauopathy-related diseases including AD. Accumulation and aggregation of hyperphosphorylated Tau as neuropil threads and neurofibrillary tangles (NFT) are pathological hallmarks of AD. Both active and passive immunisation targeting Tau protein have shown the capabilities to decrease or prevent Tau pathology and improve either motor or cognitive impairment in various animal models. In this review, we summarise recent advances in active and passive immunisation targeting pathological Tau protein, and will discuss with data obtained from both animal and human trials. Together, we give a brief overview about problems being encountered in these immunotherapies.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  16. Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions
    Lai SSM, Ng KY, Koh RY, Chok KC, Chye SM
    Metab Brain Dis, 2021 08;36(6):1087-1100.
    PMID: 33881723 DOI: 10.1007/s11011-021-00737-0
    The endosomal-lysosomal system mediates the process of protein degradation through endocytic pathway. This system consists of early endosomes, late endosomes, recycling endosomes and lysosomes. Each component in the endosomal-lysosomal system plays individual crucial role and they work concordantly to ensure protein degradation can be carried out functionally. Dysregulation in the endosomal-lysosomal system can contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). In AD endosomal-lysosomal abnormalities are the earliest pathological features to note and hence it is important to understand the involvement of endosomal-lysosomal dysfunction in the pathogenesis of AD. In-depth understanding of this dysfunction can allow development of new therapeutic intervention to prevent and treat AD.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
  17. The cellular and molecular processes associated with scopolamine-induced memory deficit: A model of Alzheimer's biomarkers
    Tang KS
    Life Sci, 2019 Sep 15;233:116695.
    PMID: 31351082 DOI: 10.1016/j.lfs.2019.116695
    Alzheimer's disease (AD) is neurodegenerative disorder that is associated with memory and cognitive decline in the older adults. Scopolamine is commonly used as a behavioral model in studying cognitive disorders including AD. Many studies have also concurrently examined the neurochemical mechanisms underlying the behavioral modifications by scopolamine treatment. Nonetheless, the scopolamine model has not become a standard tool in the early assessment of drugs. Furthermore, the use of scopolamine as a pharmacological model to study AD remains debatable. This report reviews the scopolamine-induced cellular and molecular changes and discusses how these changes relate to AD pathogenesis.
    Matched MeSH terms: Alzheimer Disease/drug therapy
  18. Deoxyelephantopin ameliorates lipopolysaccharides (LPS)-induced memory impairments in rats: Evidence for its anti-neuroinflammatory properties
    Andy SN, Pandy V, Alias Z, Kadir HA
    Life Sci, 2018 Aug 01;206:45-60.
    PMID: 29792878 DOI: 10.1016/j.lfs.2018.05.035
    AIM: Neuroinflammation is a critical pathogenic mechanism of most neurodegenerative disorders especially, Alzheimer's disease (AD). Lipopolysaccharides (LPS) are known to induce neuroinflammation which is evident from significant upsurge of pro-inflammatory mediators in in vitro BV-2 microglial cells and in vivo animal models. In present study, we investigated anti-neuroinflammatory properties of deoxyelephantopin (DET) isolated from Elephantopus scaber in LPS-induced neuroinflammatory rat model.

    MATERIALS AND METHODS: In this study, DET (0.625. 1.25 and 2.5 mg/kg, i.p.) was administered in rats for 21 days and those animals were challenged with single injection of LPS (250 μg/kg, i.p.) for 7 days. Cognitive and behavioral assessment was carried out for 7 days followed by molecular assessment on brain hippocampus. Statistical significance was analyzed with one-way analysis of variance followed by Dunnett's test to compare the treatment groups with the control group.

    KEY FINDINGS: DET ameliorated LPS-induced neuroinflammation by suppressing major pro-inflammatory mediators such as iNOS and COX-2. Furthermore, DET enhanced the anti-inflammatory cytokines and concomitantly suppressed the pro-inflammatory cytokines and chemokine production. DET treatment also reversed LPS-induced behavioral and memory deficits and attenuated LPS-induced elevation of the expression of AD markers. DET improved synaptic-functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95 and SYP. DET also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1, caspase-3 and cleaved caspase-3.

    SIGNIFICANCE: Overall, our studies suggest DET can prevent neuroinflammation-associated memory impairment and neurodegeneration and it could be developed as a therapeutic agent for the treatment of neuroinflammation-mediated and neurodegenerative disorders, such as AD.

    Matched MeSH terms: Alzheimer Disease/drug therapy
  19. Treatment of dementia with herbs: a short review
    Tang CT, Belani LK, Das S, Jaafar MZ
    Clin Ter, 2013;164(1):43-6.
    PMID: 23455743 DOI: 10.7417/T.2013.1511
    Dementia is a common symptom observed in many psychiatric and neurodegenerative diseases. Alzheimer's disease is the most common form of senile dementia seen in the general population. Multiple factors like oxidative stress, apoptosis, mitochondrial dysfunction and inflammation may be related to the neurodegenerative states. Many drugs like cholinesterase have been used for treatment but the progression of the disease still poses a challenge to the clinician. During recent times, herbs have gained much popularity as supplements because of the cost effectiveness, easy availability and fewer side effects. Early diagnosis and proper treatment may help in the prevention of mortality and morbidity concerned with any neurodegenerative disease. Understanding the cellular and molecular biology of the mode of the action of herbal products may be beneficial for researchers and clinicians. The present review article attempts to look into the potential herbal extracts which may act as an antioxidant in combating dementia.
    Matched MeSH terms: Alzheimer Disease/drug therapy
  20. Compliance and persistence with Alzheimer's disease treatment: a retrospective analysis of multiregional hospital databases in Thailand
    Kongpakwattana K, Dilokthornsakul P, Dejthevaporn C, Pattanaprateep O, Chaiyakunapruk N
    J Med Econ, 2019 Jan;22(1):26-34.
    PMID: 30303420 DOI: 10.1080/13696998.2018.1534739
    Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer's Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing "real-world" information from multiregional hospital databases in Thailand.Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan-Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR ≥ 0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR = 1.71; 95% CI = 1.21-2.42) and non-persistent (HR = 1.33; 95% CI = 1.12-1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR = 2.52; 95% CI = 1.35-4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR = 1.34; 95% CI = 1.11-1.62).Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.
    Matched MeSH terms: Alzheimer Disease/drug therapy*
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