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Alzheimer Disease: HELP
Articles from Pakistan
Based on 68 articles published since 2009
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These are the 68 published articles about Alzheimer Disease that originated from Pakistan during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease. 2019

Zaplatic, Elizabeta / Bule, Muhammed / Shah, Syed Zahid Ali / Uddin, Md Sahab / Niaz, Kamal. ·Faculty of Bioscience and Agri-Food and Environmental Technology, University of Teramo, 64100, Italy. · Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia. · Department of Pathology, Faculty of Veterinary Science, Cholistan University of Veterinary and Animal Sciences (CUVAS), Bahawalpur 63100, Pakistan. · Department of Pharmacy, Southeast University Dhaka, Bangladesh. · Department of Pharmacology and Toxicology, Faculty of Bio-Sciences, Cholistan University of Veterinary and Animal Sciences (CUVAS), Bahawalpur 63100, Pakistan. Electronic address: kniaz@unite.it. ·Life Sci · Pubmed #30914316.

ABSTRACT: Quercetin belongs to the flavonoids family, which is present in most of the plants including fruits, vegetables, green tea and even in red wine having antioxidant activities. It is available as a food supplement in the market and has physiological health effects. Quercetin has anti-inflammatory, anticancer and anti-prostate activities along with its beneficial effects on high cholesterol, kidney transplantation, asthma, diabetes, viral infections, pulmonary, schizophrenia and cardiovascular diseases. Quercetin possesses scavenging potential of hydroxyl radical (OH

2 Review Computational modeling and biomarker studies of pharmacological treatment of Alzheimer's disease (Review). 2018

Hassan, Mubashir / Abbas, Qamar / Seo, Sung-Yum / Shahzadi, Saba / Al Ashwal, Hany / Zaki, Nazar / Iqbal, Zeeshan / Moustafa, Ahmed A. ·Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Chungcheongnam 32588, Republic of Korea. · Department of Physiology, University of Sindh, Jamshoro 76080, Pakistan. · Institute of Molecular Science and Bioinformatics, Dyal Singh Trust Library, Lahore 54000, Pakistan. · College of Information Technology, United Arab Emirates University, Al‑Ain 15551, United Arab Emirates. · School of Social Sciences and Psychology, Western Sydney University, Sydney, NSW 2751, Australia. ·Mol Med Rep · Pubmed #29845262.

ABSTRACT: Alzheimer's disease (AD) is a complex and multifactorial disease. In order to understand the genetic influence in the progression of AD, and to identify novel pharmaceutical agents and their associated targets, the present study discusses computational modeling and biomarker evaluation approaches. Based on mechanistic signaling pathway approaches, various computational models, including biochemical and morphological models, are discussed to explore the strategies that may be used to target AD treatment. Different biomarkers are interpreted on the basis of morphological and functional features of amyloid β plaques and unstable microtubule‑associated tau protein, which is involved in neurodegeneration. Furthermore, imaging and cerebrospinal fluids are also considered to be key methods in the identification of novel markers for AD. In conclusion, the present study reviews various biochemical and morphological computational models and biomarkers to interpret novel targets and agonists for the treatment of AD. This review also highlights several therapeutic targets and their associated signaling pathways in AD, which may have potential to be used in the development of novel pharmacological agents for the treatment of patients with AD. Computational modeling approaches may aid the quest for the development of AD treatments with enhanced therapeutic efficacy and reduced toxicity.

3 Review Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer's and Parkinson's Diseases: An Update of Recent Data. 2018

Hussain, Ghulam / Zhang, Longbin / Rasul, Azhar / Anwar, Haseeb / Sohail, Muhammad Umar / Razzaq, Aroona / Aziz, Nimra / Shabbir, Asghar / Ali, Muhammad / Sun, Tao. ·Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. gh_azer@hotmail.com. · Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China. leocheung@hqu.edu.cn. · Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. drazharrasul@gmail.com. · Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. drhaseebanwar@gcuf.edu.pk. · Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. umar.sohail@gcuf.edu.pk. · Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. aroonarazzaq@yahoo.com. · Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. nimra.aziz1794@gmail.com. · Department of Biosciences, COMSATS Institute of Information Technology, Islamabad 44000, Pakistan. asghar.shabbir@comsats.edu.pk. · Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan. alisam007@hotmail.com. · Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China. taosun@hqu.edu.cn. ·Molecules · Pubmed #29614843.

ABSTRACT: Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-α (TNF-α), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme.

4 Review Topical Discoveries on Multi-Target Approach to Manage Alzheimer's Disease. 2018

Batool, Abida / Kamal, Mohammad Amjad / Rizvi, Syed Mohd Danish / Rashid, Sajid. ·Novel Global Community Educational Foundation, Australia. · Hazara University, Mansehra, Pakistan. · King Fahd Medical Research Center, King Abdulaziz University, Saudi Arabia. · Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770. · Department of Pharmacology & Toxicology, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia. · Quaid-e-Azam University, Islamabad, Pakistan. ·Curr Drug Metab · Pubmed #29512457.

ABSTRACT: BACKGROUND: Alzheimer's disease (AD) is recognized as progressive multifaceted and multi-factorial neurodegenerative disorder which causes dementia among elderly people. Although, researchers in this field have put considerable efforts for the investigation of novel and appropriate therapeutic measures towards the cure of AD, unfortunately, no effective prevention therapy for this disease is available till date. In fact, various aspects involved in the onset and progression of AD are still disputed or uncovered. However, to achieve definite and direct cure of AD, researcher's attention has been drawn towards exploration of new therapeutics targets. In this review, we have discussed the current progress of various aspects of pathophysiological mechanisms behind AD, together with recent investigational therapeutic approaches and present tools with an emphasis on Multi Target Directed Drugs approach. METHOD: We have scrutinized numerous peer-reviewed research articles to assemble and discuss significant research findings and success achieved in the last decade pertinent to the application of Multi-Target Directed Drugs in the treatment of AD. RESULTS: The main emphasis of the review was to understand the various aspects of pathophysiological mechanisms involved in AD, along with the recent developments on potential AD targets and application of Multi-Target Directed Drugs approach against AD. In addition, a brief overview of major drawbacks of conventional anti-AD drugs has also been included. We found that several strategies including in silico approach could be used for multi-target drug designing against AD. However, various synthetic/natural compounds and nano-formulations have the ability to be developed as multi-target drugs for AD. CONCLUSION: The present review comprises imperative information regarding AD pathology and disease process along with recent researches going on to develop treatment strategies against AD. Thus, this review might be helpful for physician, neurologist and scientist in understanding the diverse roots of AD for designing primary cure skills and scaffold of pharmacological treatment to manage AD.

5 Review Cholinesterase Inhibitory Activity of Some semi-Rigid Spiro Heterocycles: POM Analyses and Crystalline Structure of Pharmacophore Site. 2018

Hadda, Taibi Ben / Talhi, Oualid / Silva, Artur S M / Senol, Fatma Sezer / Orhan, Ilkay Erdogan / Rauf, Abdur / Mabkhot, Yahia N / Bachari, Khaldoun / Warad, Ismail / Farghaly, Thoraya A / Althagafi, Ismail I / Mubarak, Mohammad S. ·LCM Laboratory, Sciences Faculty, Mohammed Premier University, Oujda 60000, Morocco. · QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. · Department of Pharmacognosy, Pharmacy Faculty, Gazi University, Ankara-06330, Turkey. · Department of Chemistry, University of Swabi, Anbar-23561, Khyber Pakhtunkhwa, Pakistan. · Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh-11451, Saudi Arabia. · Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques., BP 384, RP 42004 Tipaza, Algeria. · Department of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus, Palestinian Territory, Occupied. · Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt. · Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, MakkahAlmukkarramah, Saudi Arabia. · Department of Chemistry, The University of Jordan, Amman11942, Jordan. ·Mini Rev Med Chem · Pubmed #28714400.

ABSTRACT: BACKGROUND: Cholinesterase family consists of two sister enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which hydrolyze acetylcholine. Since deficit of acetylcholine has been evidenced in patients of Alzheimer's disease (AD), cholinesterase inhibitors are currently the most prescribed drugs for the treatment of AD. OBJECTIVE: our aim in this article was to investigate the inhibitory potential of five known compounds (2-6) with spiro skeleton against AChE and BChE using ELISA microplate assays. In addition to their ChE inhibitory effect, their physico-chemical properties were also calculated. Moreover, the present work aims at investigating the charge/geometrical effect of a hypothetical pharmacophore or bidentate site in a bioactive group, on the inhibition efficiency of spiro compounds 2-6 by using Petra/Osiris/ molinspiration (POM) and X-ray analyses. METHOD: In the present study, five compounds (2-6) with spiro skeleton have been synthesized and tested in vitro for their inhibitory potential against AChE and BChE using ELISA microtiter plate assays at 25 µg/mL. RESULTS: Results revealed that three of the spiro compounds tested exert more than 50% inhibition against one of cholinesterases. Compound 5 displayed 68.73 ± 4.73% of inhibition toward AChE, whereas compound 6 showed 56.17 ± 0.83% of inhibition toward BChE; these two previously synthesized compounds have been the most active hits. CONCLUSIONS: Our data obtained from screening of compounds 2-6 against the two cholinesterases indicate that three of these show good potential to selectively inhibit AChE or BChE. Spiro compounds 2, 5, and 6 exhibited the most potent activity of the series against AChE or BChE with inhibition values in the range 55-70%.

6 Review Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation. 2018

Qazi, Talal Jamil / Quan, Zhenzhen / Mir, Asif / Qing, Hong. ·Beijing Key Laboratory of Separation and Analysis in Biomedical and Pharmaceuticals, Department of Biomedical Engineering, School of Life Sciences, Beijing Institute of Technology, Beijing, People's Republic of China. · Department of Bioinformatics and Biotechnology, International Islamic University Islamabad, Islamabad, Pakistan. · Beijing Key Laboratory of Separation and Analysis in Biomedical and Pharmaceuticals, Department of Biomedical Engineering, School of Life Sciences, Beijing Institute of Technology, Beijing, People's Republic of China. hqing@bit.edu.cn. ·Mol Neurobiol · Pubmed #28092081.

ABSTRACT: Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer's disease (AD), late-onset Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and autosomal dominant Alzheimer's disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.

7 Review Oxidative toxicity in diabetes and Alzheimer's disease: mechanisms behind ROS/ RNS generation. 2017

Ahmad, Waqar / Ijaz, Bushra / Shabbiri, Khadija / Ahmed, Fayyaz / Rehman, Sidra. ·School of Biological Sciences, University of Queensland, Brisbane, 4072, Australia. waqarchemist@hotmail.com. · Centre of Excellence in Molecular Biology, University of the Punjab, Thokar Niaz Baig, Lahore, 54000, Pakistan. · School of Biological Sciences, University of Queensland, Brisbane, 4072, Australia. · COMSATS Institute of Information Technology Abbottabad, Abbottabad, 22010, Pakistan. ·J Biomed Sci · Pubmed #28927401.

ABSTRACT: Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer's disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM.

8 Review Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer's and Parkinson's Disease. 2017

Braidy, Nady / Behzad, Sahar / Habtemariam, Solomon / Ahmed, Touqeer / Daglia, Maria / Nabavi, Seyed Mohammad / Sobarzo-Sanchez, Eduardo / Nabavi, Seyed Fazel. ·Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney. Australia. · School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. · Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, United Kingdom. · Attaur- Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad. Pakistan. · Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Lombardy, Italy. · Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. · Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782. Spain. ·CNS Neurol Disord Drug Targets · Pubmed #28474543.

ABSTRACT: Neurodegenerative diseases, namely Alzheimer's disease and Parkinson's disease represent a deleterious impact worldwide. Despite extensive preclinical and clinical research in neurodegenerative disorders, therapeutic strategies aimed at the prevention and chronic treatment of neurodegenerative conditions have not been successfully translated to the clinic. Therefore, the identification of novel pharmacological intervention derived from natural products is warranted. Nobiletin and tangeretin are important citrus flavonoids derived from the peel and other parts of Citrus L. genus, and have been shown to exhibit neuroprotective effects in several in vitro and in vivo studies. Apart from there antioxidant and anti-inflammatory effects, nobiletin and tangeretin have been shown to attenuate cholinergic deficits, reduce the abnormal accumulation of neurotoxic amyloid-beta peptides, reverse N-methyl- D-aspartate (NMDA) receptor hypofunction, ameliorate ischemic injury, inhibit hyperphosphorylation of tau protein, enhance neprilysin levels, modulate several signaling cascades, and protect against 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. Taken together, these naturally occurring phytochemicals may represent beneficial drug candidates for the treatment and prevention of Alzheimer's and Parkinson's disease.

9 Review A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer's disease and its prodromal stages. 2017

Rathore, Saima / Habes, Mohamad / Iftikhar, Muhammad Aksam / Shacklett, Amanda / Davatzikos, Christos. ·Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, USA. · Department of Computer Science, Comsats Institute of Information technology, Lahore, Pakistan. · Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, USA. Electronic address: christos.davatzikos@uphs.upenn.edu. ·Neuroimage · Pubmed #28414186.

ABSTRACT: Neuroimaging has made it possible to measure pathological brain changes associated with Alzheimer's disease (AD) in vivo. Over the past decade, these measures have been increasingly integrated into imaging signatures of AD by means of classification frameworks, offering promising tools for individualized diagnosis and prognosis. We reviewed neuroimaging-based studies for AD and mild cognitive impairment classification, selected after online database searches in Google Scholar and PubMed (January, 1985-June, 2016). We categorized these studies based on the following neuroimaging modalities (and sub-categorized based on features extracted as a post-processing step from these modalities): i) structural magnetic resonance imaging [MRI] (tissue density, cortical surface, and hippocampal measurements), ii) functional MRI (functional coherence of different brain regions, and the strength of the functional connectivity), iii) diffusion tensor imaging (patterns along the white matter fibers), iv) fluorodeoxyglucose positron emission tomography (FDG-PET) (metabolic rate of cerebral glucose), and v) amyloid-PET (amyloid burden). The studies reviewed indicate that the classification frameworks formulated on the basis of these features show promise for individualized diagnosis and prediction of clinical progression. Finally, we provided a detailed account of AD classification challenges and addressed some future research directions.

10 Review Neuroprotective and Neurotoxic Implications of α7 Nicotinic Acetylcholine Receptor and Aβ Interaction: Therapeutic Options in Alzheimer's Disease. 2017

Farhat, Syeda Mehpara / Ahmed, Touqeer. ·Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad - 44000. Pakistan. ·Curr Drug Targets · Pubmed #27719660.

ABSTRACT: BACKGROUND: Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. LITERATURE REVIEW: The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds to α7 nicotinic acetylcholine receptors (nAChRs) with very high affinity. This discovery has led to extensive exploration of the possible outcomes of this binding, ranging from the subcellular signaling pathways to its effects on behavioral and cognitive functions. Intriguingly, there are conflicting reports about the effects of this Aβ and α7 nAChR interaction; a few studies report a neuroprotective role of this interaction while others claim that it is neurotoxic. CONCLUSION: This review focuses on the neurotoxic and neuroprotective effects of Aβ and α7 nAChR interaction and its implications on different cell signaling pathways and other physiological functions. Moreover, the implications this interaction might have on Alzheimer's disease therapy are also discussed.

11 Review Cholinergic System and Post-translational Modifications: An Insight on the Role in Alzheimer's Disease. 2017

Ahmed, Touqeer / Zahid, Saadia / Mahboob, Aamra / Farhat, Syeda Mehpara. ·Neurobiology Laboratory, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology P.O. Box: 44000, Sector H-12, Islamabad. Pakistan. ·Curr Neuropharmacol · Pubmed #27012953.

ABSTRACT: BACKGROUND: Alzheimer's disease (AD) is the most common form of old age dementia. The formation of amyloid plaques (Aβ), neurofibrillary tangles and loss of basal forebrain cholinergic neurons are the hallmark events in the pathology of AD. LITERATURE REVIEW: Cholinergic system is one of the most important neurotransmitter system involved in learning and memory which preferentially degenerates in the initial stages of AD. Activation of cholinergic receptors (muscarinic and nicotinic) activates multiple pathways which result in post translational modifications (PTMs) in multiple proteins which bring changes in nervous system. Cholinergic receptors-mediated PTMs "in-part" substantially affect the biosynthesis, proteolysis, degradation and expression of many proteins and in particular, amyloid precursor protein (APP). APP is subjected to several PTMs (proteolytic processing, glycosylation, sulfation, and phosphorylation) during its course of processing, resulting in Aβ deposition, leading to AD. Aβ also alters the PTMs of tau which is a microtubule associated protein. Therefore, post-translationally modified tau and Aβ collectively aggravate the neuronal loss that leads to cholinergic hypofunction. CONCLUSION: Despite the accumulating evidences, the interaction between cholinergic neurotransmission and the physiological significance of PTM events remain speculative and still needs further exploration. This review focuses on the role of cholinergic system and discusses the significance of PTMs in pathological progression of AD and highlights some important future directions.

12 Review Resveratrol and Alzheimer's Disease: Mechanistic Insights. 2017

Ahmed, Touqeer / Javed, Sehrish / Javed, Sana / Tariq, Ameema / Šamec, Dunja / Tejada, Silvia / Nabavi, Seyed Fazel / Braidy, Nady / Nabavi, Seyed Mohammad. ·Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan. touqeer.aahmed@gmail.com. · Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan. · Department of Molecular Biology, Institute 'Ruđer Bošković', Bijenička c. 54, P.O. Box 180, 10000, Zagreb, Croatia. · Experimental Laboratory, Research Unit, Son Llàtzer Hospital, IUNICS, Ctra. Manacor km 4, 07198, Palma de Mallorca, Balearic Islands, Spain. · Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 19395-5487, Tehran, Iran. · Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia. · Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 19395-5487, Tehran, Iran. Nabavi208@gmail.com. ·Mol Neurobiol · Pubmed #26993301.

ABSTRACT: Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by progressive cognitive and memory deficits. The pathological hallmarks of AD include extracellular senile plaques and intracellular neurofibrillary tangles. Although several mechanisms have been used to explain the underlying pathogenesis of AD, current treatment regimens remain inadequate. The neuroprotective effects of the polyphenolic stilbene resveratrol (3,5,4'-trihydroxy-trans-stilbene) have been investigated in several in vitro and in vivo models of AD. The current review discusses the multiple potential mechanisms of action of resveratrol on the pathobiology of AD. Moreover, due to the limited pharmacokinetic parameters of resveratrol, multiple strategies aimed at increasing the bioavailability of resveratrol have also been addressed.

13 Review Inverse relationship between Alzheimer's disease and cancer, and other factors contributing to Alzheimer's disease: a systematic review. 2016

Shafi, Ovais. ·Sindh Medical College, Dow University of Health Sciences, Karachi, Pakistan. dr.ovaisshafi@gmail.com. ·BMC Neurol · Pubmed #27875990.

ABSTRACT: BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease. This research explores inverse relationship between AD and cancer, also investigates other factors behind AD using several already published research literature to find the etiology of AD. RESULTS: Cancer and Alzheimer's disease have inverse relationship in many aspects such as P53, estrogen, neurotrophins and growth factors, growth and proliferation, cAMP, EGFR, Bcl-2, apoptosis pathways, IGF-1, HSV, TDP-43, APOE variants, notch signals and presenilins, NCAM, TNF alpha, PI3K/AKT/MTOR pathway, telomerase, ROS, ACE levels. AD occurs when brain neurons have weakened growth, cell survival responses, maintenance mechanisms, weakened anti-stress responses such as Vimentin, Carbonic anhydrases, HSPs, SAPK. In cancer, these responses are upregulated and maintained. Evolutionarily conserved responses and maintenance mechanisms such as FOXO are impaired in AD. Countermeasures or compensatory mechanisms by AD affected neurons such as Tau, Beta Amyloid, S100, are last attempts for survival which may be protective for certain time, or can speed up AD in Alzheimer's microenvironment via C-ABL activation, GSK3, neuro-inflammation. CONCLUSIONS: Alzheimer's disease and Cancer have inverse relationship; many factors that are upregulated in any cancer to sustain growth and survival are downregulated in Alzheimer's disease contributing to neuro-degeneration. When aged neurons or genetically susceptible neurons have weakened growth, cell survival and anti-stress responses, age related gene expression changes, altered regulation of cell death and maintenance mechanisms, they contribute to Alzheimer's disease. Countermeasures by AD neurons such as Beta Amyloid Plaques, NFTs, S100, are last attempts for survival and this provides neuroprotection for certain time and ultimately may become pathological and speed up AD. This study may contribute in developing new potential diagnostic tests, interventions and treatments.

14 Review Why therapies for Alzheimer's disease do not work: Do we have consensus over the path to follow? 2016

Amtul, Zareen. ·Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. ·Ageing Res Rev · Pubmed #26375861.

ABSTRACT: Alzheimer's disease (AD) represents a personal tragedy of enormous magnitude, which imposes a daunting worldwide challenge for health-care providers and society as well. In last five decades, global research in clinics and laboratories has illuminated many features of this sinister and eventually fatal disease. Notwithstanding this development, the Alzheimer's research apparently has come across a phase of disappointment and a little reservation about the direction to follow. Persistently distressing controversies and a significant number of missing facts shed further uncertainty about the path forward. A detailed description of some of the main controversies in AD research may assist the field towards finding a resolution. Here I reviewed some alarming concerns or controversies related to these primary issues and emphasized on a possible mechanism to settle them.

15 Review Glycation, carbonyl stress and AGEs inhibitors: a patent review. 2015

Jahan, Humera / Choudhary, M Iqbal. ·a 1 University of Karachi, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences , Karachi, Pakistan. · b 2 University of Karachi, H.E.J. Research Institute of Chemistry and Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences , Karachi, Pakistan (92-21) 111-222-292 ; (92-21) 99261713 ; iqbal.choudhary@iccs.edu. ·Expert Opin Ther Pat · Pubmed #26293545.

ABSTRACT: INTRODUCTION: The glycation process, comprising a series of reactions, results in the formation of heterogeneous adducts, known as advanced glycation end products (AGEs). AGEs are involved in several pathologies, including diabetes-associated late complications, atherosclerosis, Alzheimer's disease and inflammatory arthritis. Several inhibitors of AGEs and/or reactive carbonyl species have been identified from various sources, including natural products and synthetic molecules, and have been investigated for their mechanism of action. AREAS COVERED: This review covers the literature on AGEs inhibitors published as patents between 2001 and 2014. Initially, the earlier reported molecules with AGEs inhibitory properties, their mechanism of actions and reported adverse effects are discussed. The main focus has been on the chemical structures, methods for evaluation of the activity, modes of action, pharmacokinetics and therapeutic outcomes. The potential of these AGEs inhibitors in the treatment and management of a number of diseases are also discussed in this review. EXPERT OPINION: The reactive carbonyl species and AGEs have recently emerged as novel therapeutic targets for the prevention and treatment of several diseases. Currently, the major concerns with the use of AGEs inhibitors as therapeutic agents are low effectiveness, poor pharmacokinetics and undesirable side effects. Many of the AGEs inhibitors reviewed here possess potent antiglycation activity and are devoid of undesirable side effects. These small molecules inhibitors can, therefore, serve as scaffolds for the development and designing of new AGEs inhibitors as clinical agents.

16 Review Linking insulin with Alzheimer's disease: emergence as type III diabetes. 2015

Ahmed, Sara / Mahmood, Zahra / Zahid, Saadia. ·Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan. · Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan. saadia.zahid@asab.nust.edu.pk. ·Neurol Sci · Pubmed #26248483.

ABSTRACT: Alzheimer's disease (AD) has characteristic neuropathological abnormalities including regionalized neurodegeneration, neurofibrillary tangles, amyloid beta (Aβ) deposition, activation of pro-apoptotic genes, and oxidative stress. As the brain functions continue to disintegrate, there is a decline in person's cognitive abilities, memory, mood, spontaneity, and socializing behavior. A framework that sequentially interlinks all these phenomenons under one event is lacking. Accumulating evidence has indicated the role of insulin deficiency and insulin resistance as mediators of AD neurodegeneration. Herein, we reviewed the evidence stemming from the development of diabetes agent-induced AD animal model. Striking evidence has attributed loss of insulin receptor-bearing neurons to precede or accompany initial stage of AD. This state seems to progress with AD such that, in the terminal stages, it worsens and becomes global. Oxidative stress, tau hyperphosphorylation, APP-Aβ deposition, and impaired glucose and energy metabolism have all been linked to perturbation in insulin/IGF signaling. We conclude that AD could be referred to as "type 3 diabetes". Moreover, owing to common pathophysiology with diabetes common therapeutic regime could be effective for AD patients.

17 Review Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids? 2014

Ahmed, Touqeer / Gilani, Anwarul-Hassan. ·Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, H-12 Kashmir Highway, Islamabad, 44000, Pakistan. ·Phytother Res · Pubmed #23873854.

ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease.

18 Review A focused review of the role of ketone bodies in health and disease. 2013

Akram, Muhammad. ·Department of Eastern Medicine and Surgery, Faculty of Medical and Health Sciences, The University of Poonch , Rawalakot, Azad Jammu and Kashmir, Pakistan . ·J Med Food · Pubmed #24138078.

ABSTRACT: Ketone bodies are produced in the liver and are utilized in other tissues in the body as an energy source when hypoglycemia occurs in the body. There are three ketone bodies: acetoacetate, beta hydroxy butyrate, and acetone. Ketone bodies are usually present in the blood, and their level increases during fasting and starvation. They are also found in the blood of neonates and pregnant women. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones.

19 Article Huperzine-A response to cognitive impairment and task switching deficits in patients with Alzheimer's disease. 2019

Gul, Amara / Bakht, Jehan / Mehmood, Farah. ·Department of Applied Psychology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan. · Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan. ·J Chin Med Assoc · Pubmed #30839402.

ABSTRACT: BACKGROUND: Alzheimer's Disease (AD) is associated with cognitive decline due to various pathological mechanisms. There are several acetylcholinesterase inhibitor compounds which can improve cognition, but Huperzine-A is a natural sesquiterpene alkaloid extracted from Chinese herb (Huperzia Serrata) which has rapid action. METHODS: Double blind study was conducted. Participants included 50 patients with AD and 50 healthy individuals. Patients were recruited from Civil and BV hospital Bahawalpur and Nishter hospital Multan, Pakistan during May 2017 until February 2018 who were stable on Huperzine-A medication. Patients were tested twice. First, at the time of diagnosis to determine baseline scores. Second, post eight weeks of Huperzine-A treatment. Healthy individuals had single testing session. Participants completed Addenbrooke's Cognitive Examination and Trail Making Test. RESULTS: Patients with AD showed cognitive and task switching deficits in contrast with healthy individuals. There was significant improvement in cognition and task switching abilities post Huperzine-A treatment compared with baseline performance. CONCLUSION: Huperzine-A is effective in reducing cognitive and task switching deficits in patients with AD.

20 Article The exploration of novel Alzheimer's therapeutic agents from the pool of FDA approved medicines using drug repositioning, enzyme inhibition and kinetic mechanism approaches. 2019

Hassan, Mubashir / Raza, Hussain / Abbasi, Muhammad Athar / Moustafa, Ahmed A / Seo, Sung-Yum. ·College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea. · College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea; Department of Chemistry, Government College University, Lahore, 54000, Pakistan. · School of Social Sciences and Psychology & MARCS Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia; Department of Social Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar. · College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea. Electronic address: dnalove@kongju.ac.kr. ·Biomed Pharmacother · Pubmed #30551512.

ABSTRACT: Novel drug development is onerous, time consuming and overpriced process with particularly low success and relatively high enfeebling rates. To overcome this burden, drug repositioning approach is being used to predict the possible therapeutic effects of FDA approved drugs in different diseases. Herein, we designed a computational and enzyme inhibitory mechanistic approach to fetch the promising drugs from the pool of FDA approved drugs against AD. The binding interaction patterns and conformations of screened drugs within active region of AChE were confirmed through molecular docking profiles. The possible associations of selected drugs with AD genes were predicted by pharmacogenomics analysis and confirmed through data mining. The stability behaviour of docked complexes (Drugs-AChE) were checked by MD simulations. The possible therapeutic potential of repositioned drugs against AChE were checked by in vitro analysis. Taken together, Cinitapride displayed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD.

21 Article Drug Design of Inhibitors of Alzheimer's Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives. 2019

Hadda, Taibi Ben / Rauf, Abdur / Zgou, Hsaine / Senol, Fatma Sezer / Orhan, Ilkay Erdogan / Mabkhot, Yahia Nasser / Althagafi, Ismail I / Farghaly, Thoraya A / Alterary, Seham. ·LCM, Department of Chemestry, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco. · Department of Geology, University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Pakistan. · Ibn Zohr University, Polydisciplinary Faculty, Ouarzazate 45000, Morocco. · Department of Pharmacognosy, Pharmacy Faculty, Gazi University, Ankara 06330, Turkey. · Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. · Department of Chemistry, Umm Al-Qura University, Mecca, Saudi Arabia. · Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt. · Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh-11451, Saudi Arabia. ·Mini Rev Med Chem · Pubmed #30387392.

ABSTRACT: BACKGROUND: Since deficit of acetylcholine has been evidenced in the Alzheimer's disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD. METHOD: In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity. RESULTS AND CONCLUSION: All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

22 Article In Silico Identification of Novel Apolipoprotein E4 Inhibitor for Alzheimer's Disease Therapy. 2019

Bano, Saddia / Rasheed, Muhammad Asif / Jamil, Farrukh / Ibrahim, Muhammad / Kanwal, Sumaira. ·Research Center for Modelling and Simulations, National University of Sciences and Technology Islamabad, Pakistan. · Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan. ·Curr Comput Aided Drug Des · Pubmed #30306878.

ABSTRACT: INTRODUCTION: Apolipoprotein E4 (ApoE) is a major genetic factor for developing Alzheimer's disease (AD). It plays a vital role in brain to maintain a constant supply of neuronal lipids for rapid and dynamic membrane synthesis. Aggregation of beta amyloid plaques (Aβ) and neurofibrillary tangles in brain are responsible for onset of AD. The current study is designed to predict a drug against over activity of apoE4. 22 natural compounds (marine, microorganism and plant derivative) were used in current study. METHODS: These compounds were used as inhibitors to target apoE4 protein activity. Moreover, six synthetic compounds were docked with target protein to compare and analyze the docking results with natural compounds. S-Allyl-L-Cysteine, Epicatechin Gallate and Fulvic acid showed highest binding affinity (-7.1, - 7 and -7 kcal /mol respectively). Analysis of the docked complex showed that Epicatechin Gallate bonded with Gln156 and Asp35. Furthermore, Fulvic Acid showed hydrogen bonding with Glu27. Among synthetic compound, Tideglusib had highest binding affinity with target protein but did not show hydrogen bonding with any amino acid residue. Moreover, a natural compound S-Allyl-LCysteine also showed highest binding affinity but did not show hydrogen bonding with any amino acid residue. RESULTS AND CONCLUSION: Our study highlighted Epicatechin Gallate as a potential lead compound on the basis of binding affinity and hydrogen bonding to inhibit the progression of AD.

23 Article Biaryl scaffold-focused virtual screening for anti-aggregatory and neuroprotective effects in Alzheimer's disease. 2018

Khalid, Sidra / Zahid, Muhammad Ammar / Ali, Hussain / Kim, Yeong S / Khan, Salman. ·Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. · Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. · Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, South Korea. · Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. skhan@qau.edu.pk. ·BMC Neurosci · Pubmed #30424732.

ABSTRACT: BACKGROUND: Alzheimer's disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aβ) protein. Aβ is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme 'transmembrane aspartyl protease, β-secretase'. Inhibition of β-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with Aβ peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, β-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD. RESULTS: Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets. CONCLUSION: These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered.

24 Article Neuroprotective, antidiabetic and antioxidant effect of Hedera nepalensis and lupeol against STZ + AlCl 2018

Hashmi, Waleed Javed / Ismail, Hammad / Mehmood, Furrukh / Mirza, Bushra. ·Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. · Department of Biochemistry and Biotechnology, University of Gujrat, Gujrat, 50700, Pakistan. · Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. bushramirza@qau.edu.pk. ·Daru · Pubmed #30353379.

ABSTRACT: PURPOSE: This study was aimed to evaluate the effect of Hedera nepalensis crude extract (HNC) and its isolated compound lupeol on antioxidant defence system, biochemical parameters and behavioural indices of Alzheimer disease generated in diabetic rats. METHODS: To evaluate the effect of the plant extract and lupeol, symptoms of Alzheimer and diabetes were induced in rats by STZ + AlCl RESULTS: HNC significantly reduced blood glucose level in a time dependent manner and elevated liver function markers were significantly (P < 0.05) reinstated to normal levels. HNC showed increase in level of catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH). HPLC quantification revealed that HNC treatment led to significant (p < 0.001) elevation in the level of neurotransmitters (dopamine and serotonin) in the midbrain region as compared to Alzheimer control (AC) group. EPM and MWM test showed decrease in cognitive and memory impairment in a rat group treated with HNC as compared to AC group. CONCLUSION: Overall, results showed that H. nepalensis has therapeutic potential for the treatment of diseases like Alzheimer and diabetes. Graphical abstract Therapeutic effect of Hedera nepalensis K. Koch and lupeol against STZ + AICI

25 Article 2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer's diseases: In vitro and in silico studies. 2018

Abbasi, Muhammad Athar / Hassan, Mubashir / Ur-Rehman, Aziz / Siddiqui, Sabahat Zahra / Hussain, Ghulam / Shah, Syed Adnan Ali / Ashraf, Muhammad / Shahid, Muhammad / Seo, Sung Yum. ·College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea; Department of Chemistry, Government College University, Lahore, 54000, Pakistan. Electronic address: abbasi@gcu.edu.pk. · College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea. · Department of Chemistry, Government College University, Lahore, 54000, Pakistan. · Faculty of Pharmacy and Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. · Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan. · Department of Biochemistry, University of Agriculture, Faisalabad, 38040, Pakistan. · College of Natural Science, Department of Biological Sciences, Kongju National University, Gongju, 32588, South Korea. Electronic address: dnalove@kongju.ac.kr. ·Comput Biol Chem · Pubmed #30245349.

ABSTRACT: The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (1; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound 1 with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) in a basic, polar and protic medium to obtain the parent sulfonamide 3 which was then treated with different electrophiles, 4a-g, in a polar and aprotic medium to acquire the designed molecules, 5a-g. These convergent derivatives were evaluated for their inhibitory potential against α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for α-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer's diseases.

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