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      Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs

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          Abstract

          Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as “dementia”, “Alzheimer's,” “traditional medicine,” “ethnopharmacology,” “ethnobotany,” “herbs,” “medicinal plants” or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.

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          Most cited references247

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          Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

          The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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            Alzheimer's disease.

            Alzheimer's disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease--ie, plaques, composed of amyloid beta (Abeta), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Abeta metabolism. By contrast with familial disease, sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies.
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              Discovery and resupply of pharmacologically active plant-derived natural products: A review

              Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                12 February 2018
                2018
                : 10
                : 3
                Affiliations
                [1] 1Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University , Nainital, India
                [2] 2Institute of Genetics and Animal Breeding of the Polish Academy of Sciences , Jastrzebiec, Poland
                [3] 3Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy , Cluj-Napoca, Romania
                [4] 4ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary Medicine , Cluj-Napoca, Romania
                [5] 5Department of Molecular Biology and Biochemical Pharmacology, Institute of Molecular Biology Roumen Tsanev, Bulgarian Academy of Sciences , Sofia, Bulgaria
                [6] 6Department of Pharmacognosy, University of Vienna , Vienna, Austria
                Author notes

                Edited by: Athanasios Alexiou, Novel Global Community Educational Foundation (NGCEF), Hebersham, Australia

                Reviewed by: Gjumrakch Aliev, GALLY International Biomedical Research, United States; Mohammad Hassan Baig, Yeungnam University, South Korea

                *Correspondence: Atanas G. Atanasov a.atanasov.mailbox@ 123456gmail.com

                †These authors have contributed equally to this study.

                Article
                10.3389/fnagi.2018.00003
                5816049
                29483867
                5b6d8e71-b694-44ab-8267-b6b2dc2dbeaf
                Copyright © 2018 Tewari, Stankiewicz, Mocan, Sah, Tzvetkov, Huminiecki, Horbańczuk and Atanasov.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 October 2017
                : 08 January 2018
                Page count
                Figures: 11, Tables: 3, Equations: 0, References: 283, Pages: 24, Words: 17505
                Funding
                Funded by: Krajowy Naukowy Osrodek Wiodacy 10.13039/501100008648
                Award ID: 05-1/KNOW2/2015
                Categories
                Neuroscience
                Review

                Neurosciences
                alzheimer's disease,amyloid fibrils,β-amyloid,dementia,ethnopharmacology,herbal drugs
                Neurosciences
                alzheimer's disease, amyloid fibrils, β-amyloid, dementia, ethnopharmacology, herbal drugs

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