BIOCHEMICAL TARGETS OF PLANT BIOACTIVE COMPOUNDS A pharmacological reference guide to sites of action and biological effects GIDEON POLYA CRC P R E S S Boca Raton London New York Washington, D.C Library of Congress Cataloging-in-Publication Data Polya, Gideon Maxwell Biochemical targets of plant bioactive compounds : a pharmacological reference guide to sites of action and biological effects Gideon Polya p cm Includes bibliographical references and index ISBN 0-415-30829-1 Materia medica, Vegetable-Handbooks, manuals, etc Botanical chemistry-Handbooks, manuals, etc Plant products-Handbooks, manuals, etc Pharmacology-Handbooks, manuals, etc Plants-Metabolism-Handbooks, manuals, etc I Title RS164 P766 2003 2002155281 61 5l.32-dc21 This book contains information obtained from authentic and highly regarded sources Reprinted material is quoted with permission, and sources are indicated A wide variety of references are listed Reasonable efforts have been made to publish reliable data and information, but the authors and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher The consent of CRC Press does not extend to copying for general distribution, for promotion, for creating new works, or for resale Specific permission must be obtained in writing from CRC Press for such copying Direct all inquiries to CRC Press, 2000 N.W Corporate Blvd., Boca Raton, Florida 3343 Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe Visit the CRC Press Web site at www.crcpress.com O 2003 by CRC Press No claim to original U.S Government works International Standard Book Number 0-41 5-30829- Library of Congress Card Number 2002 155281 Printed in the United States of America Printed on acid-free paper Contents List of tables Preface Plant defensive compounds and their molecular targets I I 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Introduction I Organization and scope ofthe book Descr$tion of the tables Using the tables The structural diversiiy of plant defensive compounds Plant alkaloids Plantphenolics 21 Plant te9enes 33 Other plant compounds 4 Biochemistry - the chemistry of life 2.1 2.2 2.3 2.4 2.5 Introduction water-based l$ Protein structure Engmes and ligand-binding proteins Metabolic strategies 66 Inhibition of biochemicalprocesses by plant defensiue compounds 85 - Neurotransmitter- and hormone-gated ion channels 3.1 Introduction electrical signalling in excitable cells 86 3.2 Ionotropic neurotransmitter receptors neurotransmitter-gatedzon channels 88 3.3 Structure andfunction of ionotropic receptors 88 - - Ion pumps, ligand- and voltage-gated ion channels 4.1 Introduction 123 4.2 Ion pumps 123 4.3 Voltage-gatedNui channels 4.4 Ligand-regulated and voltage-gated K'+ channels 4.5 Voltage-gated Ca" channels vi Contents 4.6 4.7 Ligand-gated Ca" channels Chloride transport and voltage-regulated chloride channels 127 Plasma membrane G protein-coupled receptors 5.1 5.2 5.3 5.4 5.5 5.6 Introduction signalling via heterotrimeric Gproteins 157 G protein-coupled hormone and neurotransnzitter receptors Hormones and neurotransmitters acting via G protein-coupled receptors Activation of spec$c G protein-coupled receptors Leucocyte and inzamnzation-related G protein-linked receptors Other G protein-coupled receptors 164 - Neurotransmitter transporters and converters 6.1 6.2 6.3 6.4 6.5 Introduction Synthesis of neurotransmitters Release of neurotransmittersjonz synaptic vesicles 3 Re-uptake of neurotransnzitters into neurons and synaptic vesicles 233 Neurotransmitter degradation 3 Cyclic nucleotide-, c a + and nitric oxide-based signalling 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Introduction ~ a " and calmodulin-dependent engymes A d ~ y i y cyclase 5 l Manbrane-bound and soluble guanyiyl cyclases 5 Nitric oxide synthesis Cyclic A M P - and cyclic GMP-dependentprotein kinases Protein kinase honzologies and phosphoprotein phosphatases Cyclic nucleotide phosphodiesterases 8 Signal-regulated protein kinases Introduction Cyclic AMP-dependent protein kinase Cyclic GMP-dependent protein kinase Protein kinase C Ca2+-calnzodulin-dependentprotein kinases AMP-dependent protein kinase 9 Receptor !yrosine kinases 0 Protein kinase B Cytokine activation oftheJAK'/STATpathw(/~ Cell cycle control 3 Receptor serine/threonine kinases 3 Other protein kinases 3 Phosphoprotein phosphatases Contents Gene expression, cell division and apoptosis 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9 9.10 vii 339 Introduction 339 Regulation of gene expression in prokaryotes 339 Regulation of transcr$tion in eukaryotes 340 M A processing and translation Control of translation 342 Protein processing and post-translational mody5cation 343 Protein targeting Cell division and apoptosis 344 HIVI infection and HIVI replication 345 Plant compounds intefering with gene expression 10 Taste and smell perception, pheromones and semiochemicals 10.1 0.2 10.3 10.4 10.5 10.6 10.7 10.8 10.9 10.10 Introduction Sweet taste receptors Bitter taste receptors 397 Saliy taste perception Sour taste perception 398 Umami jplutamate taste perception) Odorant perception Animal pheronzones and other animal bioactivesproduced by plants 399 Otherplant senziochemicals affecting aninzal behaviour 399 Odoriferous animal metabolites of ingestedplant compounds 399 11 Agonists and antagonists of cytosolic hormone receptors 11.1 11.2 11.3 11.4 Introduction 452 Steroid hormones 452 Non-steroid cytosolic hormone receptor ligands 453 Plant bioactives affecting cytosolic receptor-mediated signalling 454 12 Polynucleotides, polysaccharides, phospholipids and membranes 12.1 12.2 12.3 12.4 Introduction 487 Po~ynucleotides488 Poiysaccharides and 01ip.osaccharides 489 Phosphol$ids and membranes 490 13 Inhibitors of digestion and metabolism 13.1 13.2 13.3 13.4 13.5 13.6 13.7 Introduction 51 Giycohydrolases 51 Proteases 518 Giyco&sisand tricarboxylic acid cycle 522 Mitochondria1 electron transport and oxidativephospho~ylation 522 Gluconeogenesis 523 Solute translocation 524 487 viii Contents 14 Anti-inflammatory, antioxidant and antidiabetic plant compounds 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 Introduction Adhesion and movement of inzammatocy leucocytes Chemokines Phagocytosis Kinins, ~ytokines,platelet activatingfactor and eicosanoids Plant-derived anti-inJamnzatory conqounds 9 Diabetes nzellitus and plant antidiabetic compounds 9 Summary 601 Appendix: structures of key parent and representative compounds Bibliography Compound index Plant genus index Plant common names index Subject index Abbreviations Tables Nicotinic acetylcholine receptor agorlists and antagonists Iorlotropic y-aminobutyric acid and benzodiazepirle receptors Iorlotropic glutamate, glycirle and serotonin receptors Sigma and vanilloid receptors Ca'+-A~Pase, f , K+-ATPase and Naf, K f -ATPase H Voltage-gated Na+ channel Ligand- and voltage-gated K+ channels + Voltage- and ligand-gated Ca2+channels and ~ a /Ca2+ antiporter CFTR, voltage-gated C channels and Naf -K+-'LC1 co-transporter Adenosine receptors Muscarinic acetylcholirle receptor Adrenergic receptors Dopamine receptors Metabotropic GABA(B)-,glutamate- and serotonin-receptors Opiate receptors Leucocyte- and inflammation-related G protein-coupled receptors Other G protein-linked receptors G protein-interacting plant compounds Synthesis of rleurotransmitters Release of neurotransmitters from syrlaptic vesicles Re-uptake of neurotransmitters into neurons and synaptic vesicles Acetylcholinesterase Morloamirle oxidase Degradation of other neurotransmitters Calmodulirl Adenylyl cyclase and guanylyl cyclase Nitric oxide synthesis Cyclic nucleotide phosphodiesterases Eukaryote protein kirlases Activation of protein kirlase C by ~lant-derived phorbol esters Receptor tyrosine kinase-mediated signalling Phosphatidylirlositol 3-kinase Phosphoproteirl phosphatases Ribosome-inactivating polynucleotide aminoglycosidases Protein synthesis x Tables DNA-dependent RNA and DNA synthesis and topoisomerases Dihydrofolate reductase and thymidylate synthetase HIV- integrase and HIV- reverse transcriptase Actin, histone acetylase, histone deacetylase, cell division and tubulin Apoptosis-inducing plant compounds Sweet plant compounds Bitter plant compounds Sour (acid) tasting plant compounds Odorant plant compounds Animal pheromones and defensive agents occurring in plants Some further plant-derived semiochemicals Odoriferous human products of ingested plant compounds Agonists and antagonists of cytosolic steroid hormone receptors Cytosolic non-steroid hormone receptor agonists and antagonists Polynucleotide-binding compounds Lectins and polysaccharide hydrolases Non-protein plant compounds permeabilizing membranes Plant proteins directly or indirectly perturbing membranes Inhibition of glycosidases by plant non-protein compounds Plant a-amylase inhibitor (aAI) proteins Plant polygalacturonase-inhibiting proteins Inhibition of proteases by plant non-protein compounds Inhibition of proteases by plant proteins Oxidative phosphorylation and photophosphorylation Multidrug resistance, glucose and other transporters Various enzymes Plant lipoxygenase and cyclooxygenase inhibitors Antioxidant free radical scavengers Pro-oxidant compounds Antioxidant enzyme induction and pro-inflammatory blockage Aldose reductase and aldehyde reductase inhibitors Plant compounds with hypoglycaemic, antidiabetic and/or insulinotropic effects Subject index Usambarensine 10 Usaramine 13 Umea 27 Usnic acid 27 Uterine endometrium 452 Uterus 167, 173, 185, 224, 245,452 U T P 19, 73, 74, 77,78, 164 UV 29 Vacuole 46, 52, 79,81, 82 Valepotriate 36 Valerenic acid 37 Valerian 9, 36 Valeriana 9, 36 Valerianaceae 9, 36 Valine 53 Valproic acid 234 Valtratum 36 Van der Waals 57, 60 Vane 16,620 Van Gogh 107, 132,219,407,428,447 Vanicoside 23 Vanilla 22 Vnnilla 22 Vanilloid R 37, 39, 90, 119, 121, 122 Vascular cell adhesion molecule 596 Vascular dilation 256, 258, 298, 300, 595 Vascular endothelial growth factor 336,600 Vascular permeability 595, 598, 599 Vasicinol 15 Vasicinone 15 Vasoactive 94, 100, 113, 118, 120, 134, 136, 144, 146-53, 159, 167, 168, 174, 178, 181, 182, 184-90, 196, 197, 199,201,212,213, 217,2224,226,228,229,232,245,25394, 321, 335,407,547,572,575,601-20 Vasoactive intestinal peptide 167, 232 Vasoconstriction 164, 167 Vasodilation 90, 163, 253-94, 595, 599 Vasopressin 159, 167, 224, 232 Vasopressin R 228, 229 Vasorelaxant 27, 275 Vegetarian 94 Vehicle exhaust 57 Venus fly trap 16,465 Npris 15 Veprisinium 15 Veraguensin 24 Verapamil 126 Veratridine 125 Eratrum 9,125 Verbascone 18 Verlaine 107 Vermeerin 38 Vernodalin 37 Vernodalol 37 Ernonia 37 835 Vesicant 354,633 Vesicle sorting 82 Vesicular monoamine transporter 240-1 Vesicular re-uptake 232 Vesicular transporter 233 Vessel permeability 595 Vestitol 32 Vetch 49 Vetiver grass 37 Ntiueria 37 a-Vetivone 37 p-Vetivone 37 Viagra 258,294 Vibrio 157 Vicenin 29 Vicenin-2 29 Vicia 1, 49 Vicianin 49 Vicine Vietnam War 584, 633 Vigilance 165 Vinblastine 11, 344 Vincristine 11, 344 Vinegar 397, 398,415 Vinegar aroma 429 Viola 36 Violaceae 36 Violet 36 Violet aroma 425 Viral dsRNA 342 Viral infection 304 Viral replication 302 Virol 47 Virola snuff 197, 198 Virus 110, 131, 168, 170, 190, 211,230, 259, 26 1, 266, 284, 286, 287, 13, 14, 16, 322, 329,333,339,342,344-9,352-5,364,365, 374, 376, 380, 383, 388, 389,408,461,462, 464, 465, 477,483,492, 533, 537, 538, 547, 561,562,574,580,581,583,586,587,610, 612,625,636,639,640,643,645,646 Viscosity 72 Vision 43, 125, 158, 174, 258, 397 Visnadin 28 Visnagin 27 Vitaceae 25 Vitamin 20,60 Vitamin A 43, 44,454 Vitamin A deficiency 48 Vitamin A poisoning 48 Vitamin BI 20, 1, 60 Vitamin BI deficiency 591 Vitamin B,, 20, 60 Vitamin B, 20, 60 Vitamin B12 20 Vitamin C 46, 343, 63 Vitamin C deficiency 63 836 Subject index Vitamin D 452 Vitamin D,, 454 Vitamin D? 454 Vitamin D deficiency 454, 486 Vitamin D R 485, 486 Vitamin E 600 Vitamin H 20 Vitamin K 343,470,539 Vitamin K I 25, 28 Vitamin P 623, 624 Vitexin 29 Vitilego 419 Etis 25 Volatile isoprenoid 396 Voltage-gated Ca" channel 87, 88, 125, 126, 146-52, 160, 161,231,253 Voltage-gated C channel 155 Voltage-gated ion channel 87, 88, 123 Voltage-gated K + channel 125, 126, 142, 145, 146 Voltage-gated Na' channel 17, 39, 125, 126, 135, 136, 137, 138, 139, 140, 141 Voltage-regulated C channel 128, 155 Voltage-sensitive Na' channel 398 Vomiting 90 Von Bulow 657 Von Euler 90 Von Euler-Chelpin 584 Von Muralt 586 V-snare 344 Vulgaxanthin 10 Wild 480 Walker 560 M'alsh-Krebs inhibitor 296 War 1,5, 121,233,236,247 Warburg 563 Warburganal 37 Wasp 441,442,449,450 Water 52, 53, 55, 57,66, 67, 81, 82 Water-based 52 Water contamination 585 Water hemlock 47 Water reabsorption 167 Water retention 453 Watson 358 M'augh 63 Wax 48 W i s s 368 Welsh 239, 243 West Africa 119, 168, 172, 179, 190 West African stimulant 110, 203, 240 West Bengal 32 1, 585 Western Australia 13 Western Europe 11, 189 West Indies 323, 405 Wheat 17,51 Wheat germ agglutinin 489 M'hooping cough 157 M7ieland 93, 117, 204, 368, 388 M'ighteone 32 M'ilde 107 M7ilkins 358 M'illardiine 48 M'illiams 41 3, 583 M7ills 1, 59 M'illstatter 174, 240, 568, 62 M'indaus 12,486 M7ine 623 Wine aroma 435 Miitch 11, 189, 335 Wzthanza 18 M'ithasomnine 18 Withering 131 M70ad 10, 15,264,478,602 M'obble position 77 M'ogonin 29 M701fsbane 9, 136 M'ollstonecraft 63 M'oodward 116, 117, 198,357,395,407,459, 491,509,510 M'ool 346 M'orld M'ar 204, 248, 262, 280, 281, 11, 530,565,569,571,620 M'ormwood 35 M'orst smell 43 M70undhealing 36, 318, 521, 556, 557, 654, 656 M'ounding 47, 302, 397, 520, 532, 546, 551, 595 Wucherena 442 M'yerone acid 47 M'yerone acid methyl ester 47 Xanthine 20 Xanthine oxidase 23, 28, 32, 592, 593 Xanthinin 38 Xanthochymol 22 Xantholide 38 Xanthone 21,27,32,33 Xanthone-C'glycoside 32, 33 Xanthone-0-glycoside 32, 33 Xanthopsia 132,407,447 Xanthotoxin 28 Xanthotoxol 28 Xanthoxylin 22 Xanthumin 38 X chromosome 75 Xenobiotic 20,48,453, 524 Xenopu.5 303 Xerophthalmia 48 X-ray crystallography 56 Xylopia 11 Xylopine 11 Xylopinine 11 Xylose 44 P-Xylosidase 526 Subject index Xylulose 44 Xylulose-5-phosphate 69 Yakuchinone 23 Yam 392 Yangona 105, 106, 139, 250 Yaqona 105, 106, 139,250 Y chromosome 75 Yeast 353, 584 Yeast fermentation 67 Yellow perception 447 Yellow period 407 Yellow vision 132, 407 Yemen 187 Yew 18,270,389,395 Yohimbe 183, 184,200,220,222 Yohimbine 10 Zaluzanin 38 Zamecnic 352 zea 18 Zearalenone 22 Zeatin 20 Zinc (zn2+) 89,520 zingiber 23, 36 Zingiberaceae 23, 304 Zingiberene 36 Zizyphine A zizyphhuc Zoapatanol 40 Zola 107 Z scheme 67 Zulu uterotonic 173 Zygophyllaceae 15 Zymogen 84,518,520 837 Abbreviations Quantitative terms (-), inhibits @, activates J, decreases or inhibits 1',increases or stimulates [A], concentration of A "C, degrees Centigrade Da, Dalton (carbon 12 mass = 12.0Da) E, energy E, redox potential Eo, standard redox potential EC,,), concentration giving 50% effect G, free energy Ga,,, activation energy H, enthalpy IC,,, concentration giving 50% inhibition I.U., international unit (pmol/min) k, rate constant for a reaction K, Kelvin A;,, dissociation constant K,,I,,,equilibrium constant Ki, enzyme-inhibitor dissociation constant K,, Michaelis-Menten constant M, molar (mol/L) MW, molecular weight P, pressure p.d., potential difference pK; -10g,~)K;~ = dissociation constant (Ail of protonated entity HA) , permeability of membrane for C1PK permeability of membrane for K f ha1 , permeability of membrane for Naf R, gas constant S, entropy 7, temperature I, V, volume F, Faraday constant ( , rc,o (FM) [XI,&;I (FM) or Ki (FM) (>x), substantial but less than 50% inhibition was obtained at a concentration of x pM; (-x), about 50% inhibition observed at x p M (at x), effect observed at x p M e, charge on ion $ transmembrane potential , A, change (e.g AG= free energy change) Other abbreviations A, adenine A, alarline 2,5-.4, 2' ,5'-oligoadenylate aA, a-amylase aa, amino acids AA, arachidorlic acid AA-TR, amino acid transporter AB, allylberlzene ABC-TR, ATP binding cassette transporter AC, adenylyl cyclase, adenylate cyclase ACAT, acylCoA: cholesterol 0-acyltransferase ACC, acetylCoA carboxylase ACE, angiotensirl converting enzyme ACE, angiotensirl I converting erlzyme ACh, acetylcholine AChE, acetylcholinesterase ACTH, adrenocorticotropic hormone ACTH-R, corticotropin (ACTH) receptor AD, Alzheimer's disease Abbreviations AD, alloxan-induced diabetic ADH, alcohol dehydrogenase ADH, antidiuretic hormone, vasopressin ADHD, attention deficit and hyperactivity disorder ADP, adenosine 5'-diphosphate '-ADP, adenosine '-diphosphate ADP-R, ADP receptor AD-R, adenosine receptor AGE, advanced glycation endproduct AHR, aldehyde reductase AI, anti-inflammatory aAI, a-amylase inhibitor Akt, insulin-activated protein kinase, PKB Ala, alanine P-Alanine-TR, p-alanine transporter ALDH, aldehyde dehydrogenase ALDO-R, aldosterone receptor Alk Pase, alkaline phosphatase ALL-DB, alloxan-induced diabetic AMCV, artichoke mottled crinkle virus AMP, adenosine 5'-monophosphate '-AMP, adenosine '-monophosphate AMPA-R, AMPA-receptor AMPK, AMP-dependent protein kinase AMPKK, AMP-dependent protein kinase kinase AMV, avian myeloblastosis virus AND-R, androgen receptor ANF, atrial natriuretic factor ANP, atrial natriuretic peptide AO, antioxidant AO/FRS, antioxidant/free radical scavenger AP, aminopeptidases AP- 1, activator protein APC, antigen presenting cell APL, allosteric potentiating ligand AR, aldose reductase a 1A-R, a 1-adrenergic receptor a2A-R, a2-adrenergic receptor Ara, arabinose, arabinoside, arabinosyl Arg, arginlne ARH-R, aryl hydrocarbon receptor AROM, cytochrome P450-linked aromatase Asn, asparagine ASNS, asparagine synthetase Asp, aspartate, aspartic acid 839 ASPPR, aspartate protease ATP, adenosine 5'-triphosphate 5'-ATP, adenosine 5'-triphosphate ATP-K+ CH, ATP-sensitive K + channel ATP-R, ATP receptor autophos'n, autophosphorylation BBB, blood brain barrier BBI, Bowman-Birk serine protease inhibitor BB-R, bombesin receptor BChE, butyryl cholinesterase BDNF, brain-derived neurotrophic factor BDNF-RTK, brain-derived neurotrophic factor receptor tyrosine kinase aBgTX, a-bungarotoxin BKAS, P-ketoacyl-ACP synthase BK-R, bradykinin receptor BZ-R, benzodiazepine receptor C, cysteine C, cytosine CA, carbonic anhydrase ~ 2CH, ~ 2channel ' ' C a + , , - C a ~ ~a2+~-calmodulin , complex C ~ + - KCH, ~2'-dependent K + channel + CAB Pase, cyclic AMP-binding phosphatase CABNase, cyclic nucleotide-binding nucleotidase cADPR, cyclic adenosine-5'-diphosphate ribose CaM, calmodulin CAM, Crassulacean acid metabolism C ~ M - C ~ ~ + - M ~ + - A C a y~ SC ~ M T P +- ~ , activated C ~ ~ + - M ? + - A T P ~ S ~ C a ~ - C a + - A T ~ a s ~2'-calmoduline, dependent C ~ + - A T P ~ S ~ CaM-FC, ~2'-dependent calmodulin fluorescence change cAMP P D E , cyclic AMP phosphodiesterase CAMP,3' ,5'-cyclic adenosine monophosphate CaM-PDE, ~2'-calmodulin-activated cyclic nucleotide phosphodiesterase CaM-CAMP PDE, Ca2+-calmodulindependent cAMP phosphodiesterase CaM-PK I-IV, ~2'-calmodulin-activated protein kinases I-IV CaM-PK, ~2'-calmodulin-activated protein kinase 840 Abbreviations CaMPKs I-IV, calmodulin-dependent protein kinases I-IV CART, cocaine- and amphetamineregulated transcript CART-R, cocaine- and amphetamineregulated transcript receptor CAT, catecholamine CAT-REL, vesicular catecholamine release CB-R, carnlabirloid receptor CB 1-R, CB2-R, cannabinoid receptors CBD, chitin-binding dornairl CBG, cortisol-binding globulin CBZ-R, central benzodiazepirle receptor CCK-R, cholecystokinin receptor CDC, chrysanthemum dicarboxylic acid CDK, cell division kinase, cyclin-dependent protein kinase CDK1-CDK7, cyclin-dependent protein kirlases 1-7 CDK2, cell division kirlase cDNA, complementary DNA CDP, cytidirle 5'-diphosphate CDPK, Ca'+-dependent protein kinase, calmodulin domain protein kirlase CFTR, cystic fibrosis transmembrane conductance regulator cGMP, 3',5'-cyclic guarlosirle monophosphate cGMP PDE, cyclic GMP phosphodiesterase CGRP, calcitonin-gene-related peptide ChAT, choline acetyltratlsferase CHK, chemokine CHK-R, chemokine receptor CHS, chitin synthetase CHY, c'hymotrypsirl CK, creatirle kirlase CK 1, casein kirlase CK2, casein kirlase CK-R, chemokine receptor ClC, voltage-regulated chloride channel CMC, chrysanthemum morlocarboxylic acid CMP, cytidirle 5'-monophosphate cNOS, constitutive nitric acid synthase CNS, central nervous system COLL-R, collagen receptor COMT, catechol-0-methyltransferase Corticotropin, adrerlocorticotropic hormone CORT-R, c'ortisol receptor COUP-TF, chicken ovalbumin upstream promoter transcription factor COX, cyclooxygenase COX- 1, cyclooxygenase COX-2, cyclooxygenase 2, inducible cyclooxygenase CPA, carb~x~peptidase CRE, CAMPresponse element CREB protein, CAMPresponse element (CRE) binding protein CRF, corticotropin releasing factor CRF-R, corticotropin releasing factor receptor hormorle CRH, cortic~tro~in-releasing CRH-R, corticotropin releasing hormone receptor CT- 1, cardiotrophin- CTNF, ciliary neurotrophic factor CTP, cytidirle 5'-triphosphate Cyclic AMP, adenosine 3',5'-cyclic monophosphate 3' ,5'-cyclic AMP, adenosine 3' ,5'-cyclic monophosphate Cyclic GMP, guatlosine 3',5'-cyclic monophosphate 3',5'-cyclic GMP, guarlosirle 3',5'-cyclic monophosphate CYP, cytochrome P450 oxygenase Cys, cysteirle CYSPR, cysteirle protease D, aspartate, aspartic acid D, dopamine dADP, 2'-deoxyadenosine 5'-diphosphate DAG, diac,ylglyc,erol DALS, deacetylipecoside synthase dAMP, 2'-deoxyadenosine 5'monophosphate Dansyl-CaM, dansyl-calmodulin Dansyl-CaM-FC, Ca2+ -dependent dansylcalmodulin fluorescence change dATP, 2'-deoxyadenosine 5'-triphosphate DB, diabetic DBH, dopamine-P-hydroxylase dCDP, 2'-deoxycytidine 5'-diphosphate dCMP, 2'-deoxycytidine 5'-monophosphate dCTP, 2'-deoxycytidine 5'-triphosphate dGDP, 2'-deoxyguanosine 5'-diphosphate Abbreviations dGMP, 2'-deoxyguanosine 5'monophosphate dGTP, 2'-deoxyguanosine 5'-triphosphate DHF, 7,s-dihydrofolate DHFR, dihydrofolate reductase DHPhe, dihydrophenyl DIFP, diisopropylfluorophosphate DM, diabetes mellitus DNA GAAL, DNA glycosylase/apurinic/ apyrimidirlic lyase DNA, deoxyribonucleic acid DNAH, DNA helicase DNAL, DNA ligase DNAP, DNA-dependent DNA polymerase DNAS, DNA synthesis DPPH, 1,l -diphenyl-2-picrylhydrazyl radical D-R, dopamirle receptor D 1-R, D2-R, dopamirle receptors D-REL, vesicular dopamirle release dsDNA, double stranded DNA dTDP, 2'-deoxythymidine 5'-diphosphate dTMP, 2'-deoxythyrnidine 5'-monophosphate D-TR, dopamine transporter dTTP, 2'-deoxythymidine 5'-triphosphate E, glutamate, glutamic acid EAE, experimental autoimmune encephalomyelitis EC, Enzyme Commission ECDY-R, ecdysone receptor ECE, endothelin-converting enzyme ECMOX, cytochrome P450-dependent ecdysone 20-monooxygenase eEF-2, eukaryote elongation factor EF, elongation factor EGF, epidermal growth factor EGF-RTK, epidermal growth factor receptor tyrosine kinase eIF2, eukaryote initiation factor eIF2aK, eukaryote initiation factor a kinase ELA, elastase END, endothelirl END-R, erldothelirl receptor eNOS, endothelial nitric oxide syrlthase EPO, erythropoietin ER, endoplasmic reticulum ERE, estrogen response element 841 ERK, external signal-regulated protein kinase (MAPK) EST-R, estrogen receptor ETC, electron transport chain F, phenylalanine F26BP, fructose-2,6-bisphosphate FA, fatty acid FAD, fatty acid desaturase FADHJFAD, reduced/oxidized flavin adenine dinucleotide FI-ATPase,ATP syrlthetase F I complex FGF, fibroblast growth factor FGF-RTK, fibroblast growth factor receptor tyrosine kirlase Fmet, formylmethionirle FMNH2/FMN, reduced/oxidized flavin monorlucleotide FPTase, farnesyl-protein transferase FR, free radical FRS, free radical scavenger Fru, fructose, fructoside, fructosyl FSH, follicle stimulating hormone Fuc, fucose, fucoside, fucosyl G protein, heterotrimeric guarlyl nucleotide-binding protein G, glycirle G, guanine G-6-P-TR, glucose-6-phosphate transporter GABA, y-aminobutyric acid GABAA-R, GABA(A) receptor GABAA-R, ionotropic GABA(A) receptor GABAB-R, metabotropic GABA(B)receptor iGABA-R, ionotropic GABA receptor GABAT, GABA transaminase GABA-TR, GABA transporter Gal, galactose, galactoside, galactosyl GALLDH, I.-galactono-y-lactone dehydrogerlase GalN, galactosamine, galactosaminoside, galactosamirlosyl GalNac, Kacetyl galactosamine, Kacetylgalactosaminoside, Kacetylgalactosaminosyl GAP, GTPase activating protein Gastrin-R, gastrin receptor GC, guanylyl cyclase, guanylate cyclase 842 Abbreviations G-CSF, granulocyte colony stimulating factor GDP, guanosine 5'-diphosphate GEF, guarlyl rlucleotide exchange factor GH, growth hormone GHB, y-hydroxybutyrate GHB-R, y-hydroxybutyrate receptor GH-RIF, growth hormone-release inhibiting factor, somatostatin GI, gastro-intestinal GIP, gastric inhibitory peptide, glucosedependent irlsulirlotropic polypeptide Glc, P-11-glucose Glc, glucose, glucoside, glucosyl, P-11glucopyranosyl, P-11-glucopyranoside GlcA, glucuronic acid, glucuronide, glucuronyl GlcN, glucosamine, glucosarninoside, glucosamirlosyl GlcNAc, N-acetylglucosamine, Kacetylglucosarninoside, Kacetylglucosamir~osyl Glc-R(GIP), glucose receptor for GIP secretion Glc-TR, glucose transporter Gln, glutamirle GLP- 1, glucagon like peptide- Glu, glutamate, glutamic acid GluDC, glutamate decarboxylase Glu-R, glutamate ionotropic receptor Gly, glycine Gly-R, glycine receptor GMP, guanosine 5'-monophosphate GNDF, glial cell line-derived rleurotrophic factor GNDF-RTK, glial cell line-derived neurotrophic factor receptor tyrosine kirlase GN-R, glucagon receptor GPCR, G protein-coupled receptor GPI, guinea pig ileum relaxation by opioid GRH, gonadotropin-releasing hormone GS, glycogen synthase GSK3, glycogen synthase kinase GST, glutathione-S-transferase GTP, guanosine 5'-triphosphate H , histidine H , hormone HAD, histone deacetylase HAT, histone acetyl transferase Hb, haemoglobirl His, histidine HISK, histidine-specific protein kirlase HIS-R, histamine receptor HIV- 1, human immunodeficiency virus HIV- IN, HIV- irltegrase HIV-1 PR, HIV-1 protease HIV- RT, HIV- reverse transcriptase HMG protein, high mobility group protein HMGCoAR, hydroxymethylglutarylCoA reductase HPGDH, 15-hydroxyprostaglandin dehydrogerlase HPLC, high performance liquid chromatography 11PHSDH, 11-P-hydroxysteroid dehydrogerlase 17PHSOR, 17-P-hydroxysteroid oxidoreductase 5HT, serotonin 5HTlA-R, metabotropic 5-hydroxytryptamine (serotonin) receptor 5-HTl-R, metabotropic 5-hydroxytryptamine (serotonin) receptor 5HT2-R, metabotropic 5-hydroxytryptamine (serotonin) receptor 5HT3-R, ionotropic 5-hydroxytryptamine receptor 5HT-R, 5-hydroxytryptamine (serotonin) receptor 5HT-REL, serotonin (5HT) release 5HT-REL, vesicular serotonin release HYAL, hyaluronidase HypoGlc, hypoglycaemic I, isoleucine IKB,inhibitor of NF-KB IKB,inhibitor of nuclear factor KB I1-R, 12-R, imidazoline Rs IDD, iodide deficiency disorder IDDM, insulin-dependent diabetes mellitus IFN-y, interferon-? IFNy-R, interferon-? receptor IFNs, interferons IGF-RTK, insulin-like growth factor receptor tyrosine kinase IGF- 1, insulin-like growth factor- Abbreviations IGF- 1-RTK, insulin-like growth factor- receptor tyrosine kinase IGF-2, insulin-like growth factor-2 IGF-2-RTK, insulin-like growth factor-2 receptor tyrosine kinase iGlu-R, inhibitory glutamate receptor IKK, inhibitor KBkinase IL, interleukin IL- 1P, interleukin- 1P IL- 1P-R, interleukin- 1P receptor IL- 1, interleukin- IL-8, interleukin-8 IL-8-R, interleukin-8-receptor Ile, isoleucine Im, imidazole iNOS, inducible nitric oxide synthase Inr, initiation region INS-RTK, insulin receptor tyrosine kinase IP, intraperitoneal IP3, inositol- l,4,5-triphosphate IP3-R, inositol-l,4,5-triphosphate receptor I Q , isoquinoline I-R, imidazoline R IRS and IRS2, insulin receptor substrates ITD, iodothyronine deiodinase JAK, Janus kinase JH, juvenile hormone K, lysine KAL, kallikrein KATI and IWTII, kynurenine aminotransferases I and I1 KPI, Kunitz protease inhibitor K-R, kainate receptor KTI, ICunitz trypsin inhibitor L, leucirle LARI, lens aldose reductase inhibitor L-Ca2+C~, L-type voltage-gated C G + channel LDL, low density lipoprotein Leu, leucirle LH, luteinizing hormone LH-R, luteirlizirlg hormone receptor LHRH, luteinizing hormone release hormone LIF, leukaemia inhibitory factor 843 LOX, lipoxygenase 5-LOX, 5-lipoxygenase 12-LOX, 12-lipoxygenase 15-LOX, 15-lipoxygenase LPS, lipopolysaccharide LT, leukotriene LTB,,, leukotriene B4 LTP, lipid transfer protein, non-specific lipid transfer protein L-type Ca2+ C H , L-type Calf channel Lys, lysine M, methionine mACh-R, muscarinic acetylcholine receptor Man, mannose, mannoside, mannosyl MAO, monoamine oxidase MAO-A and MAO-B, monoamine oxidases MAPK, mitogen activated protein kinase (ERK) MAPKK, MAPK kinase, mitogen activated protein kinase kinase MAPKKK, MAPK kinase kinase, mitogen activated protein kinase kinase kinase MARCKS, myristoylated alanine-rich C kinase substrate MA-TR, monoamine transporter MCP- 1, monocyte chemoattractant protein MC-R, a-melanocyte-stimulating hormone (a-MSH) receptor MD, n~ethylenedioxy MDR-TR, multidrug-resistance transporter Met, methionine mGlu(1-8)-Rs, metabotropic glutamate receptors mGlu-R, metabotropic glutamate receptor MHC, major histocompatibility complex MHCP, methylhydroxychalcone polymer MLC, myosi~l light chain MLCK, ~a'+-calmodulin-dependent myosin light chain kinase MLV, murine leukaemia virus MMP, matrix metalloprotease MPR, metalloprotease mRNA, messenger RNA MSG, monosodium glutamate (glutamate) a-MSH, melanocyte-stimulating hormone 844 Abbreviations MT, microtubule MT-R, melatonin receptor MVD, mouse vas deferens relaxation by opioid N, asparagine Na+/Glc T R , Na+/glucose symport transporter ~ a + / ~ T R+ N a + / c i + antiporter g , transporter N ~ + / H + R , N ~ + / H + R antiporter T T transporter ~ a + / K + / c l - R , Na+-K+-2ClT co-transporter NAADP, nicotinic acid adenine dinucleotide 2'-phosphate NAADP-R, nicotinic acid adenine dinucleotide 2'-phosphate receptor nACh-R, nicotinic acetylcholine receptor NADH DH, NADH dehydrogenase NADH/NAD+, reduced/oxidized nicotinamide adenine dinucleotide NADH-UQOR NADH-ubiquinone oxidoreductase NADPH/NADP+, reduced/oxidized nicotinamide adenine dinucleotide phosphate Nase, nucleotidase NBD, nucleotide-binding domain of ABC-TR NDP, nucleoside 5'-diphosphate NE, norepinephrine NEP, neutral endopeptidase NE-REL, vesicular norepinephrine release NeuNac, N-acetylneuraminic acid (sialic), N-acetylneuraminoside (sialoside), N-acetylneuraminosyl acid (sialosyl) NEUT, neurotensin NEUT-R, neurotensin receptor NFKB,nuclear factor KB NFAT, nuclear factor of activated T cells NGF, nerve growth factor NGF-RTK, nerve growth factor receptor tyrosine kinase NIDDM, non-insulin-dependent diabetes mellitus n-m, nicotinic-muscarinic NM, neuromuscular NMDA, N-methyl-11-aspartate NMDA-Glu-R, Kmethyl-11-aspartatebinding glutamate receptor NMP, nucleoside 5'-monophosphate nNOS, neurorlal nitric oxide synthase NO, nitric oxide, non-NMDA-Glu-R, non-NMDA-binding glutamate receptor NOS, nitric oxide synthase NPY, neuropeptide Y NQOR, NADPH:quinone oxidoreductase (DT-diaphorase) NT, neurotratlsmitter NTP, nucleoside 5'-triphosphate N-type Ca'+ CH, N-type Ca'+ channel ODC, ornithine decarboxylase OD-R, odorant receptor - R , opiate receptor OSM, oncostatin M OTCase, ornithine transcarbamoylase Ox phos., oxidative phosphorylation OX-R, oxytocin receptor P, proline P561c6 K , lck tyrosine kinase T PA, platelet aggregation PADPRH, poly(ADP-ribose)glycohydrolase PAF, platelet activating factor, 1-0-alkyl-2acetyl-sn-glycero-3-phosphorylcholine PAF-R, platelet-activating factor receptor PAG, polynucleotide aminoglycosidases PAG, polynuc1eotide:adenosine glycosidase PAI, platelet aggregation inhibitor PAI- 1, plasminogen activator inhibitor- PAR, protease-activated receptor PB, phenylprop- 1-ene PBZ-R, peripheral benzodiazepine receptor P-Ci2+ C H , P-type voltage-gated ~ ' channel PDB-R, phorbol dibutyrate receptor (PKC) PDGF, latel let-derived growth factor PDGF-RTK, platelet-derived growth factor receptor tyrosine kinase PDPK, phosphatidylinositol lipiddependent PK Abbreviations PE, phorbol ester PEP, phosphoenolpyruvate PEP, prolyl endopeptidase PEPCK, PEP carboxykinase PEPCK, phosphoenolpyruvate carboxylase PfCDPK, Plasmodiumfalciparum Ca'+dependent protein kinase PG, polygalacturonase PG, prostagla~ldin PGH2S, prostaglandin Hz synthase PGIP, polygalacturonase inhibiting protein PGK, 3-phosphoglycerate kinase PGP-TR, P-glycoprotein transporter PG-R, prostaglandin receptor PGS?prostaglandin synthetase PH domain, pleckstrin homology domain Phe, phenyl Phe, phenylalanine phos'n, phosphorylation PhosbK, phosphorylase b kinase PI, protease inhibitor PISK, phosphatidylinositol-3-kinase P13,4P2, phosphatidylinositol-3,4bisphosphate P14,5P2, phosphatidylinositol-4,5bisphosphate P13,4,5P3, phosphatidylinositol-3,4,5trisphosphate PK, protein kinase PKA, CAMP-dependentprotein kinase PKA, cyclic AMP-dependent protein kinase PKB, insulin-activated protein kinase, Akt PKC, Ca'+- and phospholipid-dependent protein kinase, protein kinase C PKG, cGMP-dependent protein kinase PLAs, phospholipase A2 PLC, phospholipase C PLCy, phospholipase C y PLD phospholipase D PM NADH OX, plasma membrane NADH oxidase PM, plasma membrane POMC, preopiomelanocortin PP, phosphoprotein phosphatase PPZB, calcineurin, ~a'+-dependent phosphoprotein phosphatase 845 PPZC, M i +-dependent phosphoprotein phosphatase PPA-R, peroxisome proliferator-activated receptor PPC, proprotein convertase PRL, prolactin Pro, proline PROG-R, progesterone receptor ProH, prolyl hydroxylase PROP, 6-propylthiouracil PRP, pathogenesis related protein PS, protein synthesis PSI, photosystem I PSI, protein synthesis inhibitor (inhibition) PSII, photosystem I1 PSTase, phenolsulphotransferase PT, peptidyltransferase PTH, parathyroid hormone PTH-R, parathyroid hormone/ parathyroid hormone-related protein receptor PTPases, P-Tyr phosphatases PUVA therapy, psoralen with ultraviolet A light therapy PYK, pyruvate kinase Q, glutamine Q, quinone R, arginlne R, receptor R, R group of amino acid 5aR, testosterone 5a-reductase o-R, sigma receptor (metabotropic or ionotropic) R / S domain, highly conserved ricin/asarcin-interacting domain of 28s rRNA RA-R, retinoic acid receptor RER, rough endo~lasmic reticulum Rha, rhamnose, rhamnoside, thamnosoyl, a-I,-rhamnopyranosyl, a-1'rhamnopyranoside RI, ribosome inactivation Rib, ribose, riboside, ribosyl RIP, ribosome-inactivating protein RLV, Raucher leukaemia virus RNA, ribonucleic acid 846 Abbreviations RNAP, DNA-dependent RNA polymerase RNAS, RNA synthesis ROS, reactive oxygen species rRIP, recombinant RIP RRL, rabbit reticulocyte lysate (for in uitro PSI measurement) rRNA, ribosomal RNA RT, reverse transcriptase RTK, receptor tyrosine kinase RY-R, ryanodine receptor, STAT, signal transducers and activators of transcription Steroid X R, steroid X receptor STX, saxitoxin STZ-DB, streptozotocin-induced diabetic SUB, subtilisin Succinate DH, succinate dehydrogenase SU-R, sulphonylurea receptor (ATP-K+ CH) S, serine S Am., South American 70s PS, 70s ribosome (prokaryote) protein synthesis s PS, s ribosome (eukaryote) rotei in synthesis SAR, systemic acquired resistance S 1P, sphingosine- 1-phosphate S 1P-R, sphingosine- 1-phosphate receptor SBG, steroid binding globulin SEC-R, secretin receptor SEP, squalene epoxidase Ser, serine SERPR, serine protease SialylT, sialyltransferase SLOX, soya bean 15-lipoxygenase, soya bean lipoxygenase SNFlK, SNFl protein kinase kinase s PT, s ribosome (eukaryote) peptidyl transferase snRNA, small nuclear RNA snRNPs, small nuclear ribonucleoproteins SP, substance P SPH-R, sphingosine receptor SP-R, substance P receptor Src, a soluble tyrosine kinase SRIF, somatotropin release inhibiting factor, somatostatin SRIF-R, somatostatin (somatotropin release inhibiting factor) receptor SRP, signal recognition particle S-S, disulphide SSADH, succinic semialdehyde dehydrogenase SSAR, succinic sernialdehyde reductase ssDNA, single stranded DNA SSV, simian sarcoma virus T, thymine T, threonine T3, triiodothyronine T4, tetraiodothyronine TBPS, tertiary-butylbicyclophosphorothioate TCA, tricarboxylic acid TF, transcription factor TGF-P, transforming growth factor P TGF-P-Rs, transforming growth factor receptors TGL, triglyceride lipase THPhe, tetrahydrophenyl Thr, threonine THY-R, thyroid hormone receptor TIME tissue inhibitor of metalloprotease T K , tyrosine kinase TLC, thin layer chromatography TLRs, Toll-like receptors oxidase TMAOX, trimeth~lamine TM\! tobacco mosaic virus TNF, tumour necrosis factor TNF-a, tumour necrosis factor-a TNF-a-RTK, tumour necrosis factor-a receptor tyrosine kinase TOPI, DNA topoisomerase I TOPII, DNA topoisomerase I1 t-PA, tissue plasminogen activator 13-acetate TPA, 12-Tetrade~ano~lphorbol TPO, thyroid peroxidase TPP, thiamine pyrophosphate T R , transporter TIWDD, T N F receptor-associated death domain TRE, tetradecanoyl ~ h o r b oacetate (TPA) l response element T R H , thyrotropin release hormone, thyrotropin releasing hormone Abbreviations tRNA, transfer RNA Trp, tryptophan TRY, transth~uretin TRY, trypsin TS, thymidylate synthetase TSH, thyroid stimulating hormone T T X , tetrodotoxin TUB, tubulin T X , thromboxane TXA2, thromboxane A;, TXA2-R, thromboxane A2 receptor TXB2, thromboxane B2 Tyr, tyrosine TYRase, tyrosinase TyrH, tyrosine hydroxylase U, uracil UDP, uridine 5'-diphosphate UDPG, uridine 5'-diphosphate a-1,glucopyranosyl ester UDP-Glc, uridine 5'-diphosphate or-1,glucopyranosyl ester UDP-glucose, uridine 5'-diphosphate or-1,glucopyranosyl ester UMP, uridine 5'-monophosphate U T E uridine 5'-triphosphate V, valine VAChTR, vesicle transporter of acetylcholirle Val, valine VAN-R, varlilloid receptor VAS-R, vasopressin (ADH, antidiuretic hormone) receptor V-Ca'+ C H , voltage-gated Ca'+ channel VEGF, vascular endothelial growth factor VEGF-RTK, vascular erldothelial growth factor-receptor tyrosirle kinase 847 VGATR, vesicle transporter of GABA and glycine VITD-R, vitamin D receptor V-K+ CH, voltage-gated K+ channel VMAT & VMAT2, vesicular monoamine transporters VMA-TR, vesicular monoamine transporter V-Naf CH, voltage-gated Naf channel W, tryptophan w.r.t., with respect to Xa, XIa, XIIa, blood clotting factors (proteases) XO, xanthine oxidase X-R, X receptor Xyl, xylose, xyloside, xylosyl Y, tyrosine Note on glycosylation abbreviations Many natural products are glycosylated and the followirlg example illustrates the abbreviations variously used here Dioscin = (25R)-Spirost-5-ene-3P-o1 3-O-a-1.-rhamnop~ranosyl-(l2)-0-[a+ I - r h a m n ~ p ~ r a n o s y l -+ 4)]-P-11-gluco(1 pyranoside) = (25R)-Spirost-5-en-3Pol 3-0-rhamnosyl- [rhamnosyll-glucoside) =(25R)- Spirost-5-en-3P-01 3-0-Rha- [Rha] Glc, noting that the [rhamnosyl] in square brackets is a sugar side chain linked to the rhatnnosyl-glucosyl residue via the rhamnosyl residue Gideon Polya is an associate Professor of Biochemistry at La Trobe University, Melbourne, Australia His research is largely concerned with plant signal transaction and plant defence I I Lb5b I S B N 0-415-30829-1 CRC PRESS ... paraguayensk (matC) (Aquifoliaceae), Coffea species (coffee) (Rubiaceae), Paullinia cupana (guarana) (Sapindaceae), Cola acuminata (cola) and Theabroma cacao (cocoa) (Sterculiaceae) and Camellia sinensis... Library of Congress Cataloging-in-Publication Data Polya, Gideon Maxwell Biochemical targets of plant bioactive compounds : a pharmacological reference guide to sites of action and biological effects. .. BIOCHEMICAL TARGETS OF PLANT BIOACTIVE COMPOUNDS A pharmacological reference guide to sites of action and biological effects GIDEON POLYA CRC P R E S S Boca Raton London New York Washington,