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      Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

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          Abstract

          In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.

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          Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

          Cláudia Saraiva, Catarina Praça, Raquel Conceição Ferreira … (2016)
          The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.
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            Amyotrophic lateral sclerosis

            Lokesh C Wijesekera, P. Leigh (2009)
            Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.
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              Ginseng compounds: an update on their molecular mechanisms and medical applications.

              Jian-Ming Lü, Qizhi Yao, Changyi Chen (2009)
              Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginsenosides, the major pharmacologically active ingredients of ginseng, appear to be responsible for most of the activities of ginseng including vasorelaxation, antioxidation, anti-inflammation and anti-cancer. Approximately 40 ginsenoside compounds have been identified. Researchers now focus on using purified individual ginsenoside to reveal the specific mechanism of functions of ginseng instead of using whole ginseng root extracts. Individual ginsenosides may have different effects in pharmacology and mechanisms due to their different chemical structures. Among them the most commonly studied ginsenosides are Rb1, Rg1, Rg3, Re, Rd and Rh1. The molecular mechanisms and medical applications of ginsenosides have attracted much attention and hundreds of papers have been published in the last few years. The general purpose of this update is to provide information of recently described effects of ginsenosides on antioxidation, vascular system, signal transduction pathways and interaction with receptors. Their therapeutic applications in animal models and humans as well as the pharmacokinetics and toxicity of ginsenosides are also discussed in this review. This review concludes with some thoughts for future directions in the further development of ginseng compounds as effective therapeutic agents.
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                Author and article information

                Contributors
                K. N. S. Sirajudeen:
                ORCID: https://orcid.org/0000-0002-8546-3412
                Journal
                Journal ID (nlm-ta): Evid Based Complement Alternat Med
                Journal ID (iso-abbrev): Evid Based Complement Alternat Med
                Journal ID (publisher-id): ECAM
                Title: Evidence-based Complementary and Alternative Medicine : eCAM
                Publisher: Hindawi
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date Collection: 2020
                Publication date (Electronic): 14 February 2020
                Publication date PMC-release: 14 February 2020
                Volume: 2020
                Electronic Location Identifier: 6565396
                Affiliations
                1Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Medical Campus, Jalan Sultan Mahmud, 20400 Kuala Terengganu, Terengganu, Malaysia
                2Department of Chemical Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
                3Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia
                Author notes

                Academic Editor: Tadaaki Satou

                Author information
                https://orcid.org/0000-0002-8546-3412
                Article
                DOI: 10.1155/2020/6565396
                PMC ID: 7042511
                PubMed ID: 32148547
                SO-VID: 2cb2d3ea-a2e0-41df-964a-62086c59f6fb
                Copyright © Copyright © 2020 Nur Shafika Mohd Sairazi and K. N. S. Sirajudeen.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 August 2019
                Date revision received : 9 December 2019
                Date accepted : 6 January 2020
                Funding
                Funded by: Universiti Sains Malaysia
                Award ID: 1001/PPSP/811203
                Award ID: 1001/PPSP/8012249
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Complementary & Alternative medicine
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine

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