DOCSLIB.ORG

Exploring Novel Treatment Approaches for Post-Traumatic Stress Disorder

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Exploring Novel Treatment Approaches for Post-Traumatic Stress Disorder Exploring novel treatment approaches for post-traumatic stress disorder Anthony Murkar Thesis submitted in partial fulfillment of the requirements of the degree of Doctor of Philosophy School of Psychology Faculty of Social Sciences University of Ottawa © Anthony Murkar, Ottawa, Canada, 2019 ii Acknowledgements I would like to express my sincerest thanks to my supervisor Zul Merali and to Pamela Kent for your continued support throughout these projects, and also for all of the amazing opportunities you made possible. Without your support I would not be where I am today. The success of these projects is a reflection of the tremendous support and supervision of you both. Your dedication to your work and love for research was an inspiration. From the day I set foot in the labs at The Royal until the day I left, never once did I feel unwelcome or unsupported. Likewise, to Jon James, Christian Cayer, Tony Durst, and John Arnason, my colleagues in the lab and outside of it who contributed to these published works: no man is an island. These projects would not have been possible without you. To the many mentors who contributed to my success, I would like to extend my thanks to you as well. To Stuart Fogel, Nafissa Ismail, and Claude Messier (the members of the thesis committee), and also to Joseph De Koninck (who was always available to lend his ear and his sage advice): your valuable input and guidance played a pivotal role in my success. Finally, to my mother, and to my friends and family throughout these years - there are too many of you to name. Your support, encouragement, and friendship uplifted me and meant more to me then you may ever realize. iii Abstract Post-traumatic stress disorder is a disorder characterized by an inability to extinguish traumatic memories and heightened reactivity to emotional stimuli. Due to the heightened resistance of traumatic memories to extinction, treatment for PTSD has been challenging and is limited to behavioral therapies targeted at reducing responsivity to threatening stimuli. Currently there are no standard pharmacological interventions that are specific to PTSD; rather, drugs used appear to target symptoms of some of the co-morbid conditions, such as anxiety (e.g. benzodiazepines) or depression (antidepressants) - which may also affect fear-memory. In this thesis, we explore the effects of natural health products (NHPs) including naturally occurring peptides and some medical botanicals on fear memory in order to explore the efficacy of natural products as potential pharmacological targets for fear-based disorders. Fear-conditioning has been used effectively in both rodents and humans to study fear- learning. Fear-conditioning is a learning paradigm during which an unconditioned aversive stimulus (such as foot shock) is paired with a neutral stimulus (such as light or tone), such that the neutral stimulus becomes associated with aversion. Fear-learning has several well- characterized stages, including acquisition, consolidation, reconsolidation, expression, and extinction that can be manipulated in order to study the pharmacological action(s) on the attenuation of learned-fear. Blockade of reconsolidation, the state during which formed memories are briefly rendered susceptible to change following recall, may provide a window of opportunity to pharmacologically diminish learned fear. In Chapter 1 of the thesis, we discuss fear-conditioning as a pre-clinical model of PTSD to explore the effects of novel pharmacological treatments on the reconsolidation process in rodents. We ultimately hope to iv provide a framework for translational work in humans for attenuating conditioned responses to trauma-related stimuli among humans with PTSD. In Chapter 2, we present evidence that systemic administration of gastrin-releasing peptide attenuates the reconsolidation of conditioned fear in rodents. Similarly, in chapter 3, we explore the effects of Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on the reconsolidation of learned-fear, and provide evidence that cannabinoid molecules may similarly prove effective at blocking the reconsolidation of conditioned fear memories. In chapter 4, we present evidence demonstrating that extracts of medical botanical Souroubea sympetala and its components may similarly block reconsolidation of conditioned fear-memory, and also exert more general anxiolytic-like activity in the elevated plus maze paradigm. Finally, in chapter 5 a general discussion considers the relative therapeutic potential for future human clinical trials of each of the three tested groups of compounds. v Co-Authorship In all cases, A. Murkar contributed to the study design, data collection, data analysis, and preparation of manuscripts. P. Kent contributed to the study design in chapters 2 and 3. J. James and C. Cayer contributed to data collection in chapters 2-4. Z. Merali contributed to the conceptualization of the study design and support to execution of all studies. Chapter 2 is published and can be cited as: Murkar, A., Kent, P., Cayer, C., James, J., & Merali, Z. (2018). Gastrin-releasing peptide attenuates reconsolidation of conditioned fear memory. Behavioural brain research, 347, 255-262. Chapter 3 is published and can be cited as: Murkar, A., Kent, P., Cayer, C., James, J., Durst, T. & Merali, Z (2019). Cannabidiol and the remainder of the plant extract modulate the effects of Δ9-Tetrahydrocannabinol on fear memory reconsolidation. Frontiers in behavioural neuroscience, 13, 174. Chapter 4 is in press and can be cited as: Murkar, A., Cayer, C., James, J., Durst, T., Arnason, J.T., & Merali, Z (in press). Extract and active principle of the neotropical vine Souroubea sympetala Gilg. block fear-memory reconsolidation. Frontiers in pharmacology. vi Table of Contents Acknowledgements ....................................................................................................................... ii Abstract ......................................................................................................................................... iii Co-authorship .................................................................................................................................v Table of contents .......................................................................................................................... vi List of figures ................................................................................................................................ ix List of abbreviations .................................................................................................................... xi Summary ...................................................................................................................................... xii 1.0 General Introduction ...............................................................................................................1 1.1 Onset and symptom clusters of PTSD ................................................................................1 1.2 Natural products as treatment ............................................................................................4 1.3 Rodent models of fear-learning and PTSD ........................................................................8 1.4 Consolidation, reconsolidation, and memory updating ..................................................10 1.5 Reconsolidation blockade ..................................................................................................16 1.6 Pathophysiology of PTSD: Role of the HPA axis and sympathetic nervous system ....18 1.7 Pathophysiology of PTSD: Fear Circuitry .......................................................................22 1.8 The role of sleep ..................................................................................................................27 1.9 Gastrin-releasing peptide ..................................................................................................29 1.10 The complex nature of cannabinoids ..............................................................................31 1.10.1 Role of CB1 in fear expression & extinction ...........................................................34 1.10.2 Role of CB1 in consolidation of learned fear ..........................................................37 vii 1.10.3 Differential effects of cannabinoid modulation at infralimbic versus prelimbic cortex .....................................................................................................................................39 1.10.4 The role of CB2 receptors .........................................................................................40 1.10.5 Summary: Cannabinoids & learned fear ................................................................41 1.11 S. Sympetala leaf extract and betulinic acid modulate learned fear ............................42 1.12 Thesis overview, objectives, & hypotheses .....................................................................44 2.0 Chapter 2: Gastrin-Releasing Peptide attenuates reconsolidation of conditioned fear-memory .................................................................................................................................47 2.1 Abstract ...............................................................................................................................48 2.2 Introduction ........................................................................................................................49
Load more

Recommended publications
  • Antioxidants and Second Messengers of Free Radicals
    antioxidants Antioxidants and Second Messengers of Free Radicals Edited by Neven Zarkovic Printed Edition of the Special Issue Published in Antioxidants www.mdpi.com/journal/antioxidants Antioxidants and Second Messengers of Free Radicals Antioxidants and Second Messengers of Free Radicals Special Issue Editor Neven Zarkovic MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editor Neven Zarkovic Rudjer Boskovic Institute Croatia Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Antioxidants (ISSN 2076-3921) from 2018 (available at: https://www.mdpi.com/journal/ antioxidants/special issues/second messengers free radicals) For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03897-533-5 (Pbk) ISBN 978-3-03897-534-2 (PDF) c 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Preface to ”Antioxidants and Second Messengers of Free Radicals” ................ ix Neven Zarkovic Antioxidants and Second Messengers of Free Radicals Reprinted from: Antioxidants 2018, 7, 158, doi:10.3390/antiox7110158 ...............
    [Show full text]
  • Betulinic Acid and Its Derivatives As Anti-Cancer Agent: a Review
    Available online a t www.scholarsresearchlibrary.com Scholars Research Library Archives of Applied Science Research, 2014, 6 (3):47-58 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-508X CODEN (USA) AASRC9 Betulinic acid and its derivatives as anti-cancer agent: A review Gomathi Periasamy*, Girma Teketelew, Mebrahtom Gebrelibanos, Biruk Sintayehu, Michael Gebrehiwot, Aman Karim and Gereziher Geremedhin Department of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia _____________________________________________________________________________________________ ABSTRACT Betulinic acid is a known natural product which has gained a lot of attention in the recent years since it exhibits a variety of biological and medicinal properties. This review provides the most important anticancer properties of betulinic acid and its derivatives. _____________________________________________________________________________________________ INTRODUCTION Cancer is a group of diseases that cause cells in the body to change and grow out of control[1]. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells keep on growing and form new cancer cells. These cancer cells can grow into (invade) other tissues, something that normal cells cannot do. In most cases the cancer cells form a tumor. But some cancers, like leukemia, rarely form tumors. Instead, these cancer cells are in the blood and bone marrow[2]. Cancer cell escape from many of the normal homeostatic mechanism that control proliferation. They invade surrounding tissues, gets into the body’s circulating system and set up areas of proliferation away from the site of their original appearance[3]. Cancer is the second most important disease leading to death in both the developing and developed countries nowadays. The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries[4].
    [Show full text]
  • Antiviral Activities of Oleanolic Acid and Its Analogues
    molecules Review Antiviral Activities of Oleanolic Acid and Its Analogues Vuyolwethu Khwaza, Opeoluwa O. Oyedeji and Blessing A. Aderibigbe * Department of Chemistry, University of Fort Hare, Alice Campus, Alice 5700, Eastern Cape, South Africa; [email protected] (V.K.); [email protected] (O.O.O) * Correspondence: [email protected]; Tel.: +27-406022266; Fax: +08-67301846 Academic Editors: Patrizia Ciminiello, Alfonso Mangoni, Marialuisa Menna and Orazio Taglialatela-Scafati Received: 27 July 2018; Accepted: 5 September 2018; Published: 9 September 2018 Abstract: Viral diseases, such as human immune deficiency virus (HIV), influenza, hepatitis, and herpes, are the leading causes of human death in the world. The shortage of effective vaccines or therapeutics for the prevention and treatment of the numerous viral infections, and the great increase in the number of new drug-resistant viruses, indicate that there is a great need for the development of novel and potent antiviral drugs. Natural products are one of the most valuable sources for drug discovery. Most natural triterpenoids, such as oleanolic acid (OA), possess notable antiviral activity. Therefore, it is important to validate how plant isolates, such as OA and its analogues, can improve and produce potent drugs for the treatment of viral disease. This article reports a review of the analogues of oleanolic acid and their selected pathogenic antiviral activities, which include HIV, the influenza virus, hepatitis B and C viruses, and herpes viruses. Keywords: HIV; influenza virus; HBV/HCV; natural product; triterpenoids; medicinal plant 1. Introduction Viral diseases remain a major problem for humankind. It has been reported in some reviews that there is an increase in the number of viral diseases responsible for death and morbidity around the world [1,2].
    [Show full text]
  • Possible Fungistatic Implications of Betulin Presence in Betulaceae Plants and Their Hymenochaetaceae Parasitic Fungi Izabela Jasicka-Misiak*, Jacek Lipok, Izabela A
    Possible Fungistatic Implications of Betulin Presence in Betulaceae Plants and their Hymenochaetaceae Parasitic Fungi Izabela Jasicka-Misiak*, Jacek Lipok, Izabela A. S´wider, and Paweł Kafarski Faculty of Chemistry, Opole University, Oleska 48, 45-052 Opole, Poland. Fax: +4 87 74 52 71 15. E-mail: [email protected] * Author for correspondence and reprint requests Z. Naturforsch. 65 c, 201 – 206 (2010); received September 23/October 26, 2009 Betulin and its derivatives (especially betulinic acid) are known to possess very interesting prospects for their application in medicine, cosmetics and as bioactive agents in pharmaceu- tical industry. Usually betulin is obtained by extraction from the outer layer of a birch bark. In this work we describe a simple method of betulin isolation from bark of various species of Betulaceae trees and parasitic Hymenochaetaceae fungi associated with these trees. The composition of the extracts was studied by GC-MS, whereas the structures of the isolated compounds were confi rmed by FTIR and 1H NMR. Additionally, the signifi cant fungistatic activity of betulin towards some fi lamentous fungi was determined. This activity was found to be strongly dependent on the formulation of this triterpene. A betulin-trimyristin emul- sion, in which nutmeg fat acts as emulsifi er and lipophilic carrier, inhibited the fungal growth even in micromolar concentrations – its EC50 values were established in the range of 15 up to 50 μM depending on the sensitivity of the fungal strain. Considering the lack of fungistatic effect of betulin applied alone, the application of ultrasonic emulsifi cation with the natural plant fat trimyristin appeared to be a new method of antifungal bioassay of water-insoluble substances, such as betulin.
    [Show full text]
  • Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line
    International Journal of Molecular Sciences Article Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line Dorina Coricovac 1,2,† , Cristina Adriana Dehelean 1,2,†, Iulia Pinzaru 1,2,* , Alexandra Mioc 1,2,*, Oana-Maria Aburel 3,4, Ioana Macasoi 1,2, George Andrei Draghici 1,2 , Crina Petean 1, Codruta Soica 1,2, Madalina Boruga 3, Brigitha Vlaicu 3 and Mirela Danina Muntean 3,4 1 Faculty of Pharmacy, “Victor Babes, ” University of Medicine and Pharmacy Timis, oara, Eftimie Murgu Square No. 2, RO-300041 Timis, oara, Romania; [email protected] (D.C.); [email protected] (C.A.D.); [email protected] (I.M.); [email protected] (G.A.D.); [email protected] (C.P.); [email protected] (C.S.) 2 Research Center for Pharmaco-toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timis, oara, Eftimie Murgu Square No. 2, RO-300041 Timis, oara, Romania 3 Faculty of Medicine “Victor Babes, ” University of Medicine and Pharmacy Timis, oara, Eftimie Murgu Square No. 2, RO-300041 Timis, oara, Romania; [email protected] (O.-M.A.); [email protected] (M.B.); [email protected] (B.V.); [email protected] (M.D.M.) 4 Center for Translational Research and Systems Medicine, Faculty of Medicine,” Victor Babes, ” University of Medicine and Pharmacy Timis, oara, Eftimie Murgu Sq. no. 2, RO-300041 Timis, oara, Romania * Correspondence: [email protected] (I.P.); [email protected] (A.M.); Tel.: +40-256-494-604 † Authors with equal contribution. Citation: Coricovac, D.; Dehelean, Abstract: Melanoma represents one of the most aggressive and drug resistant skin cancers with C.A.; Pinzaru, I.; Mioc, A.; Aburel, poor prognosis in its advanced stages.
    [Show full text]
  • Review Article Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development
    Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 238482, 26 pages http://dx.doi.org/10.1155/2015/238482 Review Article Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development Charu Sharma,1 Bassem Sadek,2 Sameer N. Goyal,3 Satyesh Sinha,4 Mohammad Amjad Kamal,5,6 and Shreesh Ojha2 1 Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE 2Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE 3DepartmentofPharmacology,R.C.PatelInstituteofPharmaceuticalEducation&Research,Shirpur,Mahrastra425405,India 4Department of Internal Medicine, College of Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA 5King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia 6Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia Correspondence should be addressed to Shreesh Ojha; [email protected] Received 24 April 2015; Accepted 24 August 2015 Academic Editor: Ki-Wan Oh Copyright © 2015 Charu Sharma et al. 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. The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are 9 numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ - tetrahydrocannabinol mediates its action through CB1/CB2 receptors.
    [Show full text]
  • Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: a Route to New Bioactive Compounds
    Review Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds Joana L. C. Sousa 1,2,*, Carmen S. R. Freire 2, Armando J. D. Silvestre 2 and Artur M. S. Silva 1,* 1 QOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal 2 CICECO, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] (C.S.R.F.); [email protected] (A.J.D.S.) * Correspondence: [email protected] (J.L.C.S.); [email protected] (A.M.S.S.); Tel.: +351-234-370-714 (A.M.S.S.) Received: 29 December 2018; Accepted: 17 January 2019; Published: 19 January 2019 Abstract: Betulinic acid (BA) and its natural analogues betulin (BN), betulonic (BoA), and 23- hydroxybetulinic (HBA) acids are lupane-type pentacyclic triterpenoids. They are present in many plants and display important biological activities. This review focuses on the chemical transformations used to functionalize BA/BN/BoA/HBA in order to obtain new derivatives with improved biological activity, covering the period since 2013 to 2018. It is divided by the main chemical transformations reported in the literature, including amination, esterification, alkylation, sulfonation, copper(I)-catalyzed alkyne-azide cycloaddition, palladium-catalyzed cross-coupling, hydroxylation, and aldol condensation reactions. In addition, the synthesis of heterocycle-fused BA/HBA derivatives and polymer‒BA conjugates are also addressed. The new derivatives are mainly used as antitumor agents, but there are other biological applications such as antimalarial activity, drug delivery, bioimaging, among others. Keywords: triterpenes; betulinic acid; betulin; betulonic acid; 23-hydroxybetulinic acid; synthesis; functionalization; derivatization 1.
    [Show full text]
  • Pdf (781.76 K)
    Sohag University Sohag Medical Journal Faculty of Medicine Saussurea costus may help in the treatment of COVID-19 Mahmoud Saif-Al-Islam Tropical Medicine and Gastroenterology Department, Sohag University Hospital, Faculty of Medicine, Egypt. Abstract Coronavirus disease 2019 (COVID-19) is an emerging disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causing an ongoing pandemic and is considered as a national public health emergency. The signs and symptoms of COVID-19 vary from mild symptoms to a fulminating disease with acute respiratory distress syndrome (ARDS) and multi-organ failure, which may culminate into death with no available vaccines or specific antiviral treatments. God provides us with important medicinal plants. Here I shall shed the light on one of these plants that may help in the treatment of COVID-19 or may even cure it. Saussurea costus (S. costus) is a popular plant with medical importance, the roots of which are widely used for healing purposes throughout human history with great safety and effectiveness. Previous studies revealed the presence of many bioactive phytochemical molecules that has antiseptic, antibacterial, antifungal, antiviral, anti- inflammatory, antioxidant, anti-lipid peroxidation, immunostimulant, immunom- odulating, analgesic, bronchodilor, hepatoprotective and antihepatotoxic properties. S. Costus has immunomodulatory effects on cytokine release and has complement- inhibitor substances helpful in the treatment of some diseases related to marked activation of the complement system, like respiratory distress. Keywords: Saussurea costus, COVID-19, respiratory distress. Background: S. costus (synonymous with widely investigated6. Various compo- Saussurea lappa), belongs to family unds isolated from the plant have Asteraceae, widely distributed in diff- medicinal properties including terp- erent regions in the world; however, enes, alkaloids, anthraquinones, and numerous species are found in India1, favonoids.
    [Show full text]
  • Plant Secondary Metabolites .Pdf
    PLANT SECONDARY METABOLITES W W W . T R C - C A N A D A . C O M +1 (416) 665-9696 www.trc-canada.com 2 Brisbane Road, Toronto [email protected] Plant Secondary Metabolites Product CAS No CAT No Acanthopanax senticosides B 114902-16-8 Please Inquire Acetyl resveratrol 42206-94-0 R150055 Acetylshikonin 24502-78-1 Please Inquire Acronycine 7008-42-6 Please Inquire Acteoside 61276-17-3 V128000 Agrimol B 55576-66-4 Please Inquire Alisol-B-23-acetate 26575-95-1 A535970 Alisol-C-monoacetate 26575-93-9 Please Inquire Alizarin 72-48-0 A536600 Alkannin 517-88-4 Please Inquire Allantoin 97-59-6 A540500 Allantoin-13C2,15N4 1219402-51-3 A540502 Alliin 556-27-4 A543530 Aloe emodin 481-72-1 A575400 Aloe-emodin-d5 1286579-72-3 A575402 Aloenin A 38412-46-3 Please Inquire Aloin A 1415-73-2 A575415 Amentoflavone 1617-53-4 A576420 Amygdalin 29883-15-6 A576840 Andrographolide 5508-58-7 A637475 Angelicin 523-50-2 A637575 Anhydroicaritin 118525-40-9 I163700 Anisodamine 55869-99-3 Please Inquire Anthraquinone 84-65-1 A679245 Anthraquinone-D8 10439-39-1 A679247 Apigenin 520-36-5 A726500 Apigenin-d5 263711-74-6 A726502 Araloside X 344911-90-6 Please Inquire www.trc-canada.com I +1 (416) 665-9696 I [email protected] Plant Secondary Metabolites Arbutin 497-76-7 A766510 Arbutin-13C6 A766512 Arctigenin 7770-78-7 A766580 Arctiin 20362-31-6 A766575 Aristolochic acid I 313-67-7 A771300 Aristolochic acid II 475-80-9 A771305 Aristolochic acid sodium salt 10190-99-5 Please Inquire Aristololactam 13395-02-3 A771200 Artemisinin 63968-64-9 A777500 Artemisinin-d3 176652-07-6
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Terpene Screening Library Item No. 9003370 • Batch No. 0611615 Panels are routinely re-evaluated to include new catalog introductions as the research evolves. Page 1 of 4 Plate Well Contents Item Number 1 A1 Unused 1 A2 Ursolic Acid 10072 1 A3 Forskolin 11018 1 A4 Betulin 11041 1 A5 Lupeol 11215 1 A6 Paxilline 11345 1 A7 β-acetyl-Boswellic Acid 11674 1 A8 Andrographolide 11679 1 A9 Bakuchiol 11684 1 A10 Betulinic Acid 11686 1 A11 β-Elemonic Acid 11712 1 A12 Unused 1 B1 Unused 1 B2 Oleanolic Acid 11726 1 B3 Neoandrographolide 11742 1 B4 Asiatic Acid 11818 1 B5 Madecassic Acid 11854 1 B6 Cafestol 13999 1 B7 Ingenol 14031 1 B8 Bilobalide 14272 1 B9 (−)-Huperzine A 14620 1 B10 Ginkgolide B 14636 1 B11 Cucurbitacin B 14820 1 B12 Unused 1 C1 Unused 1 C2 Cucurbitacin E 14821 1 C3 Polygodial 14979 1 C4 Zerumbone 15400 1 C5 Ingenol-3-angelate 16207 1 C6 Ferutinin 16554 1 C7 Limonin 16932 1 C8 Phytol 17401 1 C9 Dehydrocostus lactone 18485 1 C10 β-Elemene 19641 1 C11 Juvenile Hormone III 19646 1 C12 Unused WARNING CAYMAN CHEMICAL THIS PRODUCT IS FOR RESEARCH ONLY - NOT FOR HUMAN OR VETERINARY DIAGNOSTIC OR THERAPEUTIC USE. 1180 EAST ELLSWORTH RD SAFETY DATA ANN ARBOR, MI 48108 · USA This material should be considered hazardous until further information becomes available. Do not ingest, inhale, get in eyes, on skin, or on clothing. Wash thoroughly after handling. Before use, the user must review the complete Safety Data Sheet, which has been sent via email to your institution.
    [Show full text]
  • Biocatalysis in the Chemistry of Lupane Triterpenoids
    molecules Review Biocatalysis in the Chemistry of Lupane Triterpenoids Jan Bachoˇrík 1 and Milan Urban 2,* 1 Department of Organic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic; [email protected] 2 Medicinal Chemistry, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacký University in Olomouc, Hnˇevotínská 5, 779 00 Olomouc, Czech Republic * Correspondence: [email protected] Abstract: Pentacyclic triterpenes are important representatives of natural products that exhibit a wide variety of biological activities. These activities suggest that these compounds may represent potential medicines for the treatment of cancer and viral, bacterial, or protozoal infections. Naturally occurring triterpenes usually have several drawbacks, such as limited activity and insufficient solubility and bioavailability; therefore, they need to be modified to obtain compounds suitable for drug development. Modifications can be achieved either by methods of standard organic synthesis or with the use of biocatalysts, such as enzymes or enzyme systems within living organisms. In most cases, these modifications result in the preparation of esters, amides, saponins, or sugar conjugates. Notably, while standard organic synthesis has been heavily used and developed, the use of the latter methodology has been rather limited, but it appears that biocatalysis has recently sparked considerably wider interest within the scientific community. Among triterpenes, derivatives of lupane play important roles. This review therefore summarizes the natural occurrence and sources of lupane triterpenoids, their biosynthesis, and semisynthetic methods that may be used for the production of betulinic acid from abundant and inexpensive betulin. Most importantly, this article compares chemical transformations of lupane triterpenoids with analogous reactions performed by Citation: Bachoˇrík,J.; Urban, M.
    [Show full text]
  • Beta-Sitosterol [BSS] and Betasitosterol Glucoside [BSSG] As an Adjuvant in the Treatment of Pulmonary Tuberculosis Patients.” TB Weekly (4 Mar 1996)
    Saw Palmetto (Serenoa repens) and One of Its Constituent Sterols -Sitosterol [83-46-5] Review of Toxicological Literature Prepared for Errol Zeiger, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract No. N01-ES-65402 Submitted by Raymond Tice, Ph.D. Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709 November 1997 EXECUTIVE SUMMARY The nomination of saw palmetto and -sitosterol for testing is based on the potential for human exposure and the limited amount of toxicity and carcinogenicity data. Saw palmetto (Serenoa repens), a member of the palm family Arecaceae, is native to the West Indies and the Atlantic Coast of North America, from South Carolina to Florida. The plant may grow to a height of 20 feet (6.10 m), with leaves up to 3 feet (0.914 m) across. The berries are fleshy, about 0.75 inch (1.9 cm) in diameter, and blue-black in color. Saw palmetto berries contain sterols and lipids, including relatively high concentrations of free and bound sitosterols. The following chemicals have been identified in the berries: anthranilic acid, capric acid, caproic acid, caprylic acid, - carotene, ferulic acid, mannitol, -sitosterol, -sitosterol-D-glucoside, linoleic acid, myristic acid, oleic acid, palmitic acid, 1-monolaurin and 1-monomyristin. A number of other common plants (e.g., basil, corn, soybean) also contain -sitosterol. Saw palmetto extract has become the sixth best-selling herbal dietary supplement in the United States. In Europe, several pharmaceutical companies sell saw palmetto-based over-the-counter (OTC) drugs for treating benign prostatic hyperplasia (BPH).
    [Show full text]