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      Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

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          Abstract

          Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP +) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer’s disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

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          Ischaemic stroke

          Stroke is the second highest cause of death globally and a leading cause of disability, with an increasing incidence in developing countries. Ischaemic stroke caused by arterial occlusion is responsible for the majority of strokes. Management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy, which both reduce disability but are time-critical. Accordingly, improving the system of care to reduce treatment delays is key to maximizing the benefits of reperfusion therapies. Intravenous thrombolysis reduces disability when administered within 4.5 h of the onset of stroke. Thrombolysis also benefits selected patients with evidence from perfusion imaging of salvageable brain tissue for up to 9 h and in patients who awake with stroke symptoms. Endovascular thrombectomy reduces disability in a broad group of patients with large vessel occlusion when performed within 6 h of stroke onset and in patients selected by perfusion imaging up to 24 h following stroke onset. Secondary prevention of ischaemic stroke shares many common elements with cardiovascular risk management in other fields, including blood pressure control, cholesterol management and antithrombotic medications. Other preventative interventions are tailored to the mechanism of stroke, such as anticoagulation for atrial fibrillation and carotid endarterectomy for severe symptomatic carotid artery stenosis.
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            Neuroinflammation: friend and foe for ischemic stroke

            Stroke, the third leading cause of death and disability worldwide, is undergoing a change in perspective with the emergence of new ideas on neurodegeneration. The concept that stroke is a disorder solely of blood vessels has been expanded to include the effects of a detrimental interaction between glia, neurons, vascular cells, and matrix components, which is collectively referred to as the neurovascular unit. Following the acute stroke, the majority of which are ischemic, there is secondary neuroinflammation that both promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery. The proinflammatory signals from immune mediators rapidly activate resident cells and influence infiltration of a wide range of inflammatory cells (neutrophils, monocytes/macrophages, different subtypes of T cells, and other inflammatory cells) into the ischemic region exacerbating brain damage. In this review, we discuss how neuroinflammation has both beneficial as well as detrimental roles and recent therapeutic strategies to combat pathological responses. Here, we also focus on time-dependent entry of immune cells to the ischemic area and the impact of other pathological mediators, including oxidative stress, excitotoxicity, matrix metalloproteinases (MMPs), high-mobility group box 1 (HMGB1), arachidonic acid metabolites, mitogen-activated protein kinase (MAPK), and post-translational modifications that could potentially perpetuate ischemic brain damage after the acute injury. Understanding the time-dependent role of inflammatory factors could help in developing new diagnostic, prognostic, and therapeutic neuroprotective strategies for post-stroke inflammation.
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              TCMID 2.0: a comprehensive resource for TCM

              Abstract As a traditional medical intervention in Asia and a complementary and alternative medicine in western countries, Traditional Chinese Medicine (TCM) is capturing worldwide attention in life science field. Traditional Chinese Medicine Integrated Database (TCMID), which was originally launched in 2013, was a comprehensive database aiming at TCM’s modernization and standardization. It has been highly recognized among pharmacologists and scholars in TCM researches. The latest release, TCMID 2.0 (http://www.megabionet.org/tcmid/), replenished the preceding database with 18 203 herbal ingredients, 15 prescriptions, 82 related targets, 1356 drugs, 842 diseases and numerous new connections between them. Considering that chemical changes might take place in decocting process of prescriptions, which may result in new ingredients, new data containing the prescription ingredients was collected in current version. In addition, 778 herbal mass spectrometry (MS) spectra related to 170 herbs were appended to show the variation of herbal quality in different origin and distinguish genuine medicinal materials from common ones while 3895 MS spectra of 729 ingredients were added as the supplementary materials of component identification. With the significant increase of data, TCMID 2.0 will further facilitate TCM’s modernization and enhance the exploration of underlying biological processes that are response to the diverse pharmacologic actions of TCM.
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                01 July 2020
                July 2020
                : 18
                : 7
                : 347
                Affiliations
                [1 ]Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea; hannanbau@ 123456gmail.com (M.A.H.); rajudash.bgctub@ 123456gmail.com (R.D.); mahboobchem@ 123456gmail.com (M.A.)
                [2 ]Department of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh; sohag2010bmb.sust@ 123456gmail.com
                [3 ]Department of Fisheries Biology and Genetics, Patuakhali Science and Technology University, Patuakhali 8602, Bangladesh; habib.332@ 123456gmail.com
                [4 ]Department of Fishing and Post Harvest Technology, Sher-e-Bangla Agricultural University, Sher-e-Bangla Nagar, Dhaka 1207, Bangladesh; mmohib08@ 123456gmail.com
                [5 ]Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; ataur1981rahman@ 123456hotmail.com
                [6 ]Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea; hasan800920@ 123456gmail.com
                [7 ]ABEx Bio-Research Center, East Azampur, Dhaka 1230, Bangladesh
                [8 ]Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 780-714, Korea
                Author notes
                [* ]Correspondence: moonis@ 123456dongguk.ac.kr ; Tel.: +82-54-770-2414; Fax: +82-54-770-2447
                Author information
                https://orcid.org/0000-0001-6640-4495
                https://orcid.org/0000-0003-4128-5308
                https://orcid.org/0000-0002-8539-8905
                https://orcid.org/0000-0001-6649-3694
                https://orcid.org/0000-0003-2911-3255
                https://orcid.org/0000-0002-5188-1130
                https://orcid.org/0000-0002-1608-016X
                Article
                marinedrugs-18-00347
                10.3390/md18070347
                7401253
                32630301
                4b7b8058-2de1-40f3-96f6-2e18a71a427d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 May 2020
                : 25 June 2020
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                seaweed,secondary metabolites,neuroprotection,alzheimer’s disease,parkinson’s disease,ischemic stroke,computer-aided drug discovery

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