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      Plant Derived Phytocompound, Embelin in CNS Disorders: A Systematic Review


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          A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.

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          Characteristics of compounds that cross the blood-brain barrier

          Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transporters, adsorptive endocytosis, and the extracellular pathways. Here, we focus on the chief characteristics of two mechanisms especially important in drug delivery: transmembrane diffusion and transporters. Transmembrane diffusion is non-saturable and depends, on first analysis, on the physicochemical characteristics of the substance. However, brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can greatly alter the amount of the substance crossing the BBB. Transport systems increase uptake of ligands by roughly 10-fold and are modified by physiological events and disease states. Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes for which transporters have been described in recent years. We discuss two examples of drug delivery for newly discovered transporters: that for phosphorothioate oligonucleotides and for enzymes.
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            Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

            Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions.
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              Animal models of anxiety: do I need multiple tests?

              The combination of cutting-edge molecular technology and high-throughput phenotyping tools will not bring the expected contribution to the pre-clinical study of anxiety if not paralleled by an increase in our capacity to interpret behavioral data. Here, previous views about the multidimensional nature of emotional behaviors will be expanded and the psychological meaning and behavioral overlaps of widely used anxiety tests such as the open field, elevated plus maze and light-dark box will be discussed. It is proposed here that short-term, intra-individual variations in emotionality, although normally overlooked, constitute an important factor in the study of anxiety and can lead to unreliable estimates of the similarities between tests. The physical integration of different current tests in one single apparatus, in such a way that the emotional status of an animal becomes assessable through a series of distinct tasks, could contribute to increase reliability, rapidity and comprehensiveness in behavioral testing.

                Author and article information

                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                27 February 2017
                : 8
                Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia Selangor, Malaysia
                Author notes

                Edited by: Adolfo Andrade-Cetto, National Autonomous University of Mexico, Mexico

                Reviewed by: Benedict Green, Poisonous Plant Research Laboratory, ARS-USDA, USA; Rajendra Karki, St. Jude Children's Research Hospital, USA

                *Correspondence: Mohd. Farooq Shaikh farooq.shaikh@ 123456monash.edu

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Copyright © 2017 Kundap, Bhuvanendran, Kumari, Othman and Shaikh.

                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) or licensor 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.

                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 54, Pages: 13, Words: 9726
                Funded by: Kementerian Sains, Teknologi dan Inovasi 10.13039/501100003200
                Award ID: 06-02-10-SF0250

                Pharmacology & Pharmaceutical medicine
                embelin,cns disorders,neuropharmacology,neurodegenerative diseases,natural product


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