DOCSLIB.ORG

Toxic Polyacetylenes in the Genus Bupleurum (Apiaceae) – Distribution, Toxicity, Molecular Mechanism and Analysis Crossmark ⁎ Meiyu Lin, Weidong Zhang, Juan Su

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Toxic Polyacetylenes in the Genus Bupleurum (Apiaceae) – Distribution, Toxicity, Molecular Mechanism and Analysis Crossmark ⁎ Meiyu Lin, Weidong Zhang, Juan Su Journal of Ethnopharmacology 193 (2016) 566–573 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep Review Toxic polyacetylenes in the genus Bupleurum (Apiaceae) – Distribution, toxicity, molecular mechanism and analysis crossmark ⁎ Meiyu Lin, Weidong Zhang, Juan Su School of Pharmacy, Second Military Medical University, Shanghai 200433, China ARTICLE INFO ABSTRACT Keywords: Ethnopharmacological relevance: The genus Bupleurum includes approximately 200 species that are widely Polyacetylenes distributed in the Northern Hemisphere, Eurasia and North Africa. Certain species of this genus have long been Bupleurum used as antiphlogistic, antipyretic and analgesic agents in traditional folk medicine. As described in the Chinese Toxicity Pharmacopoeia, the roots of Bupleurum chinense DC. and B. scorzonerifolium Willd. are the herbal materials Mechanism that compose Chaihu (Radix Bupleuri), a well-known TCM herb. Quality analyses Aim of the review: This review aims to provide up-to-date and comprehensive information regarding the distribution, toxicity, molecular mechanism and relatively new methods for the qualitative and quantitative determination of polyacetylenes in different Bupleurum species. Method: The information needed for this paper were sourced from publishing sites such as Elsevier, science Direct, PubMed; electronic search engines such as Scopus and Web of Science, Google scholar; other scientific database sites for chemicals such as ChemSpider, PubChem, SciFinder, and also from on line books. Results: Polyacetylenes, which are widely distributed in genus Bupleurum of the Apiaceae family, have high toxicity. Among polyacetylenes, bupleurotoxin, acetylbupleurotoxin and oenanthotoxin have strong neurotoxi- city. Through previous research, it was found that the toxicity of Bupleurum polyacetylenes manifested as epileptic seizures, with the target of toxicity being the brain. The neurotoxicity of polyacetylenes exhibits a relationship with the γ-aminobutyric acid (GABA) receptor pathway, and polyacetylenes have been shown to inhibit GABA-induced currents (IGABA) in a competitive manner. Conclusions: The plants of genus Bupleurum have been used in traditional medicine for thousands of years. However, certain species of this genus are poisonous, and it was attributed to the high content of polyacetylenes. The present review indicates that certain polyacetylenes in the genus Bupleurum have highly neurotoxic effects. The major challenge with regard to toxic polyacetylenes is to test their neurotoxic effects in vivo as well as in further preclinical studies, which will require large amounts of purified polyacetylenes. More reference substances should be prepared, and sophisticated analytical technologies should be developed to comprehen- sively assess the quality of Radix Bupleuri herbs. These investigations will be helpful for further utilization of the plants of genus Bupleurum. 1. Introduction undesirable due to their toxic properties. Certain polyacetylenes are known to be potent skin sensitizers and have a pronounced selective Polyacetylenes are widely distributed among the families cytotoxic activity against cancer cells (Machado et al., 2002; Murdoch Umbelliferae, Araliaceae, and Asteraceae. They form a distinct group and Dempster, 2000; Ahn and Kim, 1988; Matsunaga et al., 1989; of relatively reactive natural products, and more than 1400 different Matsunaga et al., 1990). Some studies have focused on the neurotoxi- polyacetylenes and related compounds have been isolated from plants city of polyacetylenes. Polyacetylenes isolated from the roots of poison (Christensen and Brandt, 2006). Some of the polyacetylenes isolated hemlock and Oenanthe fistulosa have high neurotoxicity (Anet et al., from food plants such as carrot, celery and parsley have received much 1953; Wittstock et al., 1995; Uwai et al., 2000), and some species of the attention due to their extensive physiological impact, including anti- genus of Bupleurum have also been shown to be neurotoxic at high inflammatory, antibacterial, antifungal, anticancer, antiplatelet aggre- concentrations (Vetter, 2004; Wittstock et al., 1997). gation activities. Still, some polyacetylenes have been considered The genus Bupleurum (Family: Apiaceae) includes approximately ⁎ Corresponding author. E-mail addresses: [email protected] (W. Zhang), [email protected] (J. Su). http://dx.doi.org/10.1016/j.jep.2016.09.052 Received 12 July 2016; Received in revised form 28 September 2016; Accepted 28 September 2016 Available online 30 September 2016 0378-8741/ © 2016 Elsevier Ireland Ltd. All rights reserved. M. Lin et al. Journal of Ethnopharmacology 193 (2016) 566–573 200 species, a number of which have been pharmaceutically used for authentic Chaihu samples (Huang et al., 2011). These results indicated thousands of years, mainly in Asia and Europe (Pan, 2006; Chang and that the distribution and the contents of the tested polyacetylenes in But, 1987). Preparations containing the roots of Bupleurum species different Bupleurum species vary significantly, and they were much have been prescribed for more than 2000 years in China, where the first higher in the B. longiradiatum than in the other samples. The toxicity record about their use appeared in Shen-Nong's Herbal (Yao et al., of B. longiradiatum could readily be distinguished from other medic- 2013). Certain Bupleurum species have been used in traditional inal Bupleurum species based on polyacetylene profile. medicine in Asia for the treatment of the common cold, inflammatory Thus, in order to ensure its safety clinical use, the commercially disorders, hepatitis, cancer and fever. Radix Bupleuri, with the Chinese prepared crude drugs of Chaihu in herb markets should be labeled name Chaihu, has been widely used to treat influenza, fever, inflam- before circulation, and the qualitative and quantitative determination mation, malaria as well as menstrual disorders and is recorded as being of polyacetylenes is useful for the assessment of the toxicity of crude prepared from the roots of Bupleurum Chinense and B. scorzoner- herbal material. ifolium (Family: Apiaceae) in the Chinese Pharmacopoeia (Ikegami et al., 2006; National Commission of Chinese Pharmacopoeia, 2015). 3. Toxicity of polyacetylenes However, there are at least ten species of the genus Bupleurum (Apiaceae) that are also used locally under the name Chaihu (Pan, In general, polyacetylenes which distributed in B. falcatum, B. 2006). Even worse, B. longiradiatum, widely distributed in north- spinosum, B. salicifolium, and B. acutifolium exhibit antibacterial, eastern mainland China, is a poisonous plant that has been found in anti-inflammatory, antifungal, and anti-platelet aggregatory effects herb markets (National Commission of Chinese Pharmacopoeia, 2015). (Alanko et al., 1994; Kobaisy et al., 1997; Fujimoto et al., 1998). The misuse of B. longiradiatum as Chaihu has caused several cases of However, some polyacetylenes have been considered undesirable in human poisoning, and at least three people died after administration of Bupleurum species to their toxicant properties. Polyacetylenes are this plant, showing symptoms such as serious nausea, vomiting, known to be neurotoxic in high concentrations (Anet et al., 1953), and twitching, and opisthotonus (Pan, 2006). they have also been shown to have a pronounced selective cytotoxic The investigation of the acute toxicity of B. longiradiatum extract activity against cancer cells (Matsunaga et al., 1990). uncovered strong toxicity in mice, which was attributed to its high Radix Bupleuri represents one of the most successful and widely content of polyacetylenes (Chen, 1981; You et al., 2002). This review used herbal drugs in Asia for treatment of many diseases over the past highlights the present state of knowledge on polyacetylenes in the 2000 years. There are many adulterants of Radix Bupleuri in the herb genus Bupleurum, including their distribution, toxicity, mechanism, market (Yao, 2006; Li, et al., 2012). Among them, B. longiradiatum is quality analysis and possible relevance to human health. a representative poisonous plant which contains high concentrations of polyacetylenes. And B. longiradiatum is prohibited to be used in herb 2. Distribution of polyacetylenes in the genus Bupleurum market according to the Chinese Pharmacopoeia (2015 Edition). The misuse of B. longiradiatum as Chaihu had caused several cases of The genus Bupleurum (Family: Apiaceae) includes approximately human poisoning, and at least three people died after administration of 200 species that are widely distributed in the Northern Hemisphere, this plant, which showed symptoms such as serious nausea, vomiting, Eurasia and North Africa (Su et al., 1998). In addition to the South twitching, opisthotonus, and so on (Pan, 2006; Zhao et al., 1987). The Bupleurum and the North Bupleurum described in the Chinese surveys on B. longiradiatum demonstrated that polyacetylenes were of Pharmacopoeia, there are also other species of this genus, such as B. particular abundance in root of this plant and proved to be responsible smithivar. parvifolium, B. marginatum vat. stenophyllum, B. margin- for the toxicity of B. longiradiatum (Huang et al., 2009). As major toxic atum, B. bicaule, B.smithii, B. longiradiatum Turcz, and others. ingredients of B. longiradiatum, bupleurotoxin (1), acetylbupleurotox- Certain species of this genus, such as B. chinense, B. scorzonerifolium in (2) and oenanthotoxin (5) attracted the
Load more

Recommended publications
  • Flowering Plants Eudicots Apiales, Gentianales (Except Rubiaceae)
    Edited by K. Kubitzki Volume XV Flowering Plants Eudicots Apiales, Gentianales (except Rubiaceae) Joachim W. Kadereit · Volker Bittrich (Eds.) THE FAMILIES AND GENERA OF VASCULAR PLANTS Edited by K. Kubitzki For further volumes see list at the end of the book and: http://www.springer.com/series/1306 The Families and Genera of Vascular Plants Edited by K. Kubitzki Flowering Plants Á Eudicots XV Apiales, Gentianales (except Rubiaceae) Volume Editors: Joachim W. Kadereit • Volker Bittrich With 85 Figures Editors Joachim W. Kadereit Volker Bittrich Johannes Gutenberg Campinas Universita¨t Mainz Brazil Mainz Germany Series Editor Prof. Dr. Klaus Kubitzki Universita¨t Hamburg Biozentrum Klein-Flottbek und Botanischer Garten 22609 Hamburg Germany The Families and Genera of Vascular Plants ISBN 978-3-319-93604-8 ISBN 978-3-319-93605-5 (eBook) https://doi.org/10.1007/978-3-319-93605-5 Library of Congress Control Number: 2018961008 # Springer International Publishing AG, part of Springer Nature 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
    [Show full text]
  • Outline of Angiosperm Phylogeny
    Outline of angiosperm phylogeny: orders, families, and representative genera with emphasis on Oregon native plants Priscilla Spears December 2013 The following listing gives an introduction to the phylogenetic classification of the flowering plants that has emerged in recent decades, and which is based on nucleic acid sequences as well as morphological and developmental data. This listing emphasizes temperate families of the Northern Hemisphere and is meant as an overview with examples of Oregon native plants. It includes many exotic genera that are grown in Oregon as ornamentals plus other plants of interest worldwide. The genera that are Oregon natives are printed in a blue font. Genera that are exotics are shown in black, however genera in blue may also contain non-native species. Names separated by a slash are alternatives or else the nomenclature is in flux. When several genera have the same common name, the names are separated by commas. The order of the family names is from the linear listing of families in the APG III report. For further information, see the references on the last page. Basal Angiosperms (ANITA grade) Amborellales Amborellaceae, sole family, the earliest branch of flowering plants, a shrub native to New Caledonia – Amborella Nymphaeales Hydatellaceae – aquatics from Australasia, previously classified as a grass Cabombaceae (water shield – Brasenia, fanwort – Cabomba) Nymphaeaceae (water lilies – Nymphaea; pond lilies – Nuphar) Austrobaileyales Schisandraceae (wild sarsaparilla, star vine – Schisandra; Japanese
    [Show full text]
  • Conserving Europe's Threatened Plants
    Conserving Europe’s threatened plants Progress towards Target 8 of the Global Strategy for Plant Conservation Conserving Europe’s threatened plants Progress towards Target 8 of the Global Strategy for Plant Conservation By Suzanne Sharrock and Meirion Jones May 2009 Recommended citation: Sharrock, S. and Jones, M., 2009. Conserving Europe’s threatened plants: Progress towards Target 8 of the Global Strategy for Plant Conservation Botanic Gardens Conservation International, Richmond, UK ISBN 978-1-905164-30-1 Published by Botanic Gardens Conservation International Descanso House, 199 Kew Road, Richmond, Surrey, TW9 3BW, UK Design: John Morgan, [email protected] Acknowledgements The work of establishing a consolidated list of threatened Photo credits European plants was first initiated by Hugh Synge who developed the original database on which this report is based. All images are credited to BGCI with the exceptions of: We are most grateful to Hugh for providing this database to page 5, Nikos Krigas; page 8. Christophe Libert; page 10, BGCI and advising on further development of the list. The Pawel Kos; page 12 (upper), Nikos Krigas; page 14: James exacting task of inputting data from national Red Lists was Hitchmough; page 16 (lower), Jože Bavcon; page 17 (upper), carried out by Chris Cockel and without his dedicated work, the Nkos Krigas; page 20 (upper), Anca Sarbu; page 21, Nikos list would not have been completed. Thank you for your efforts Krigas; page 22 (upper) Simon Williams; page 22 (lower), RBG Chris. We are grateful to all the members of the European Kew; page 23 (upper), Jo Packet; page 23 (lower), Sandrine Botanic Gardens Consortium and other colleagues from Europe Godefroid; page 24 (upper) Jože Bavcon; page 24 (lower), Frank who provided essential advice, guidance and supplementary Scumacher; page 25 (upper) Michael Burkart; page 25, (lower) information on the species included in the database.
    [Show full text]
  • Fruit Anatomy of the Genus Bupleurum (Apiaceae) in Northeastern China and Notes on Systematic Implications
    South African Journal of Botany 2003, 69(2): 151–157 Copyright © NISC Pty Ltd Printed in South Africa — All rights reserved SOUTH AFRICAN JOURNAL OF BOTANY ISSN 0254–6299 Fruit anatomy of the genus Bupleurum (Apiaceae) in northeastern China and notes on systematic implications M (Rebecca) Liu1, L Shi2, B-E van Wyk1 and PM Tilney1* 1 Department of Botany, Rand Afrikaans University, PO Box 524, Auckland Park, Johannesburg 2006, South Africa 2 The Beijing Botanical Garden, Institute of Botany, The Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093, China * Corresponding author, e-mail: [email protected] Received 25 June 2002, accepted in revised form 7 November 2002 The fruit anatomy of all eight species of the genus (small vittae, large vascular bundles) — B. angustissi- Bupleurum L. mentioned in the most recent literature mum, B. bicaule, B. chinense and B. scorzonerifolium. from northeastern China was studied for the first time. This result closely supports the traditional classifica- The eight species were divided into two groups based tion system which was based on gross morphology on the shape of the mericarps in transverse section. The (plant height; leaf shape and size; involucre number, first group (round mericarps without prominent ribs) size and shape). The only exception is that B. komaro- includes B. longiradiatum and B. komarovianum, and vianum should not be close to the second group, but the second group (angular mericarps with prominent close to B. longiradiatum. Group 1 corresponds with ribs) includes B. angustissimum, B. bicaule, B. chi- Bupleurum sect. Longifolia and group 2 with sect.
    [Show full text]
  • Second Contribution to the Vascular Flora of the Sevastopol Area
    ZOBODAT - www.zobodat.at Zoologisch-Botanische Datenbank/Zoological-Botanical Database Digitale Literatur/Digital Literature Zeitschrift/Journal: Wulfenia Jahr/Year: 2015 Band/Volume: 22 Autor(en)/Author(s): Seregin Alexey P., Yevseyenkow Pavel E., Svirin Sergey A., Fateryga Alexander Artikel/Article: Second contribution to the vascular flora of the Sevastopol area (the Crimea) 33-82 © Landesmuseum für Kärnten; download www.landesmuseum.ktn.gv.at/wulfenia; www.zobodat.at Wulfenia 22 (2015): 33 – 82 Mitteilungen des Kärntner Botanikzentrums Klagenfurt Second contribution to the vascular flora of the Sevastopol area (the Crimea) Alexey P. Seregin, Pavel E. Yevseyenkov, Sergey A. Svirin & Alexander V. Fateryga Summary: We report 323 new vascular plant species for the Sevastopol area, an administrative unit in the south-western Crimea. Records of 204 species are confirmed by herbarium specimens, 60 species have been reported recently in literature and 59 species have been either photographed or recorded in field in 2008 –2014. Seventeen species and nothospecies are new records for the Crimea: Bupleurum veronense, Lemna turionifera, Typha austro-orientalis, Tyrimnus leucographus, × Agrotrigia hajastanica, Arctium × ambiguum, A. × mixtum, Potamogeton × angustifolius, P. × salicifolius (natives and archaeophytes); Bupleurum baldense, Campsis radicans, Clematis orientalis, Corispermum hyssopifolium, Halimodendron halodendron, Sagina apetala, Solidago gigantea, Ulmus pumila (aliens). Recently discovered Calystegia soldanella which was considered to be extinct in the Crimea is the most important confirmation of historical records. The Sevastopol area is one of the most floristically diverse areas of Eastern Europe with 1859 currently known species. Keywords: Crimea, checklist, local flora, taxonomy, new records A checklist of vascular plants recorded in the Sevastopol area was published seven years ago (Seregin 2008).
    [Show full text]
  • Philipp Simon Massimo Iorizzo Dariusz Grzebelus Rafal Baranski Editors the Carrot Genome Compendium of Plant Genomes
    Compendium of Plant Genomes Philipp Simon Massimo Iorizzo Dariusz Grzebelus Rafal Baranski Editors The Carrot Genome Compendium of Plant Genomes Series Editor Chittaranjan Kole, ICAR-National Research Center on Plant Biotechnology, Pusa, Raja Ramanna Fellow, Government of India, New Delhi, India [email protected] Philipp Simon • Massimo Iorizzo • Dariusz Grzebelus • Rafal Baranski Editors The Carrot Genome 123 [email protected] Editors Philipp Simon Massimo Iorizzo Vegetable Crops Research Unit Plants for Human Health Institute USDA-ARS North Carolina State University Madison, WI, USA Kannapolis, NC, USA Dariusz Grzebelus Rafal Baranski University of Agriculture in Krakow Faculty of Biotechnology and Kraków, Poland Horticulture University of Agriculture in Krakow Kraków, Poland ISSN 2199-4781 ISSN 2199-479X (electronic) Compendium of Plant Genomes ISBN 978-3-030-03388-0 ISBN 978-3-030-03389-7 (eBook) https://doi.org/10.1007/978-3-030-03389-7 Library of Congress Control Number: 2019934354 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
    [Show full text]
  • An Updated Snapshot of Recent Advances in Transcriptomics and Genomics of Phytomedicinals Biswapriya B
    PostDoc Journal Journal of Postdoctoral Research Vol. 2, No. 2, February 2014 www.postdoctoraljournal.com An Updated Snapshot of Recent Advances in Transcriptomics and Genomics of Phytomedicinals Biswapriya B. Misra Department of Biology, Genetics Institute, Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32610, USA Email: [email protected] Abstract Medicinal plants have been of great importance to human health care since the advent of medicine. A huge array of molecules has been obtained from these phytopharmaceutical-yielding species that have influenced human lives since the beginning of plant-based life-saving medicines. Some of these molecules have taken the form of taxol, aspirin, and artemisinin. With the flourishing era of high- throughput next generation sequencing technologies, a hot pursuit for sequencing the genomes and transcriptomes of these life-saving plants is underway. Although few genomes have been sequenced or are currently being addressed, the number of transcriptomes sequenced has sky-rocketed in the last couple of years and continues to surge forward with immense pace, covering all important genera of medicinal plants. I have attempted to provide the current status, progress, opportunities, and challenges of these sequencing endeavors in this comprehensive and updated review. It is my hope that this information will provide both specialists and non-specialists with the current trends and future directions of this interesting category of plants. Keywords: medicinal plant, metabolic pathway, genome, next generation sequencing, transcriptome Introduction Metabolites are small chemical entities present medicine are generally known as medicinal in living organisms with a molecular weight of plants. They belong to typical taxonomic families, less than 1000 Da.
    [Show full text]
  • Do Compositions of Lipid Fraction Correspond to Species Differentiation in Bupleurum L
    plants Article Do Compositions of Lipid Fraction Correspond to Species Differentiation in Bupleurum L. (Apiaceae)? Zhargal Alexandrovich Tykheev 1,2 , Oleg Arnoldovich Anenkhonov 3 , Svetlana Vasilievna Zhigzhitzhapova 1, Vasiliy Vladimirovich Taraskin 1 , Larisa Dorzhievna Radnaeva 1 and Faqi Zhang 4,* 1 Baikal Institute of Nature Management, Siberian Branch, Russian Academy of Sciences, 670047 Ulan-Ude, Russia; [email protected] (Z.A.T.); [email protected] (S.V.Z.); [email protected] (V.V.T.); [email protected] (L.D.R.) 2 Laboratory of the Chemistry of Natural Systems, Banzarov Buryat State University, 670000 Ulan-Ude, Russia 3 Institute of General and Experimental Biology, Russian Academy of Sciences, 670047 Ulan-Ude, Russia; [email protected] 4 Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology & Institute of Sanjiangyuan National Park, Chinese Academy of Sciences, Xining 810008, China * Correspondence: [email protected]; Tel.: +86-0971-6105845 Received: 31 August 2020; Accepted: 21 October 2020; Published: 22 October 2020 Abstract: Bupleurum L. has been widely used in various medical systems as an agent with a wide range of activities. The qualitative composition and content of lipid fraction components of the aerial parts of B. longifolium and B. chinense were elucidated in this work. The available data on the fatty acids (FAs) in Bupleurum plants were compiled and compared with species differentiation in the genus. As a result, the content of FAs in the studied Bupleurum plant species only partially corresponded to the species differentiation and, in some cases, contradicted it. The prognostic value of Bupleurum’s species differentiation for the identification of the potential composition of FAs was insignificant, and it was limited only by particular groups of species.
    [Show full text]
  • Cicuta Douglasii) Tubers
    Toxicon 108 (2015) 11e14 Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon Short communication The non-competitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglasii) tubers * Benedict T. Green a, , Camila Goulart b, 1, Kevin D. Welch a, James A. Pfister a, Isabelle McCollum a, Dale R. Gardner a a Poisonous Plant Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Logan, UT, USA b Graduate Program in Animal Science, Universidade Federal de Goias, Goiania,^ Goias, Brazil article info abstract Article history: Water hemlocks (Cicuta spp.) are acutely toxic members of the Umbellierae family; the toxicity is due to Received 22 July 2015 the presence of C17-polyacetylenes such as cicutoxin. There is only limited evidence of noncompetitive Received in revised form antagonism by C17-polyacetylenes at GABAA receptors. In this work with WSS-1 cells, we documented 9 September 2015 the noncompetitive blockade of GABA receptors by an aqueous extract of water hemlock (Cicuta dou- Accepted 14 September 2015 A glasii) and modulated the actions of the extract with a pretreatment of 10 mM midazolam. Available online 28 September 2015 Published by Elsevier Ltd. Keywords: Water hemlock Cicutoxin C17-polyacetylenes Benzodiazepines Barbiturates Midazolam Water hemlocks (Cicuta spp.) are acutely toxic members of the antagonists of the GABAA receptor by binding to the picrotoxin Umbellierae, or carrot family, that grow in wet habitats such as binding site within the chloride channel to block ion flow through streambeds or marshlands, and have been considered one of the the channel (Ratra et al., 2001; Chen et al., 2006; 2011; Olsen, most toxic plants of North America for many years (Kingsbury, 2006).
    [Show full text]
  • Dissertation
    DISSERTATION Titel der Dissertation „Isolation of positive, allosteric GABAA receptor modulators from Chinese herbal drugs traditionally used in the treatment of anxiety and insomnia“ Verfasserin Mag. pharm. Judith Singhuber angestrebter akademischer Grad Doktorin der Naturwissenschaften (Dr.rer.nat.) Wien, 2011 Studienkennzahl lt. A 091 449 Studienblatt: Dissertationsgebiet lt. Dr.-Studium der Naturwissenschaften Pharmazie Studienblatt: Betreuerin / Betreuer: Univ. Prof. Mag. Dr. Brigitte Kopp For Maximillian & Lennox ACKNOWLEDGMENTS In this place I would like to thank the people which contributed to the success of my thesis: Prof. Brigitte Kopp, my supervisor, for providing an interesting topic and for her guidance. Prof. Steffen Hering (Department of Pharmacology and Toxicology, University of Vienna) for the possibility to work in his Department. Dr. Igor Baburin (Department of Pharmacology and Toxicology, University of Vienna) for the pharmacological investigations on the 56 extracts and the HPLC fractions of A. macrocephala and C. monnieri. Dr. Sophia Khom (former Department of Pharmacology and Toxicology, University of Vienna) for her assistance as well as interesting discussions on GABAergic neurotransmission and other topics. Prof. Gerhard F. Ecker (Department of Medicinal Chemistry) for the binary QSAR and help with the pharmacophore model. Prof. Ernst Urban (Department of Medicinal Chemistry, University of Vienna) und Prof. Hanspeter Kählig (Institute of Organic Chemistry, University of Vienna) for the NMR- measurements. Dr.
    [Show full text]
  • Antioxidant, Antimicrobial Activities and Fatty Acid Components of Leaf and Seed of Bupleurum Lancifolium Hornem
    Journal of Medicinal Plants Research Vol. 5(16), pp. 3758-3762, 18 August, 2011 Available online at http://www.academicjournals.org/JMPR ISSN 1996-0875 ©2011 Academic Journals Full Length Research Paper Antioxidant, antimicrobial activities and fatty acid components of leaf and seed of Bupleurum lancifolium Hornem. Ali Shafaghat Department of Chemistry, Islamic Azad University, Germi Branch, Germi, Iran. E-mail: [email protected]. Accepted 14 June, 2011 The hexane extracts of leaf and seed of Bupleurum lancifolium Hornem, which were collected from northwestern Iran, were obtained by Soxhlet apparatus. The fatty acids were derived to methyl esters and determined by gas chromatography/flame ionization detector (GC/FID) and gas chromatography/ mass spectrometry (GC/MS) systems. The hexanic extract from the leaf and seed contained ω-3 (17.1 and 48.1% respectively). The other main components of the leaf and seed extracts were ω-6 (14.1 and 22.2%), palmitic acid (25.7 and10.1%) and γ-linolenic acid (GLA) (21.3 and 8.2%), respectively. The hexane extracts of leaf and seed from B. lancifolium detected as an important source of ω-3 and ω-6 compounds among several Bupleurum species. The antioxidant activity of both hexane extracts was evaluated by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) method. The results indicate that hexane extracts from different parts of B. lancifolium possess considerable antioxidant activity. The highest radical scavenging activity was detected in seed (IC 50 = 125 µg/ml). The antimicrobial activity of the extracts of those samples were determined against seven Gram-positive and Gram-negative bacteria ( Bacillus subtilis , Enterococcus faecalis , Staphylococcus aureus , S.
    [Show full text]
  • Glutamate-Gated Chloride Channel Receptors and Mechanisms of Drug Resistance in Pathogenic Species
    Glutamate-gated chloride channel receptors and mechanisms of drug resistance in pathogenic species Mohammed Atif B. Pharmacy, M. Pharmacy (Pharmacology) A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2019 Queensland Brain Institute Dedicated to my beloved parents & my demised brother who I miss everyday ii Thesis Abstract Pentameric ligand-gated ion channels (pLGICs) are important therapeutic targets for a wide range of neurological disorders that include cognitive impairment, stroke, psychiatric conditions and peripheral pain. They are also targets for treating parasite infections and controlling pest species in agriculture, veterinary practice and human health. Here we focus on one family of the pLGICs i.e., the glutamate-gated chloride channel receptors (GluClRs) which are expressed at inhibitory synapses of invertebrates. Ivermectin (IVM) is one of the main drugs used to control pest species and parasites, and it works by activating GluClRs in nematode and arthropod muscle and nerves. IVM resistance is becoming a major problem in many invertebrate pathogens, necessitating the development of novel anti-parasitic drugs. This project started with the simple aim of determining the sensitivity to glutamate and IVM of GluClRs from two different pest species: the parasitic nematode Haemonchus contortus (HcoGluClRs) and the mosquito malaria vector Anopheles gambiae (AgGluClRs). In chapter 3, we found that the β homomeric GluClRs of H.contortus were insensitive to IVM (EC50> 10 µM), whereas α homomeric HcoGluClRs were highly sensitive (EC50 = 20 nM). Heteromeric αβ HcoGluClRs exhibited an intermediate sensitivity to IVM (EC50 = 135 nM). By contrast, the EC50 values for glutamate at α homomeric and αβ heteromeric receptors were not distinguishable; falling between 20-30 µM.
    [Show full text]