Toxicological Survey of African Medicinal Plants Thispageintentionallyleftblank Toxicological Survey of African Medicinal Plants Edited by Victor Kuete Faculty of Science University of Dschang, Cameroon AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON(cid:129)NEWYORK(cid:129)OXFORD PARIS(cid:129)SANDIEGO(cid:129)SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO Elsevier 32JamestownRoad,LondonNW17BY 225WymanStreet,Waltham,MA02451,USA Firstedition2014 Copyright©2014ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronic ormechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem, withoutpermissioninwritingfromthepublisher.Detailsonhowtoseekpermission,further informationaboutthePublisher’spermissionspoliciesandourarrangementwithorganizations suchastheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatour website:www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher (otherthanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperience broadenourunderstanding,changesinresearchmethods,professionalpractices,ormedicaltreatment maybecomenecessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingand usinganyinformation,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformation ormethodstheyshouldbemindfuloftheirownsafetyandthesafetyofothers,includingpartiesfor whomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assume anyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability, negligenceorotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideas containedinthematerialherein. BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-12-800018-2 ForinformationonallElsevierpublications visitourwebsiteathttp://store.elsevier.com ThisbookhasbeenmanufacturedusingPrintOnDemandtechnology.Eachcopyisproducedtoorder andislimitedtoblackink.Theonlineversionofthisbookwillshowcolorfigureswhereappropriate. Contents Preface xxi ListofContributors xxiii 1 ToxicologicalSocietiesinAfrica:RolesandImpact inPolicyMakingandLivingConditions 1 JulesC.N.Assob,DicksonS.Nsagha,NevilleMvoNgum andVictorKuete 1.1 Introduction 1 1.2 ToxicologicalSocietiesinAfrica 2 1.2.1 AfricanSocietyforToxicologicalSciences 2 1.2.2 SocietyofEnvironmentalToxicologyandChemistry 4 1.2.3 WestAfricanSocietyofToxicology 5 1.2.4 CameroonSocietyforToxicologicalSciences 5 1.2.5 The“AssociationTunisiennedeToxicologie” 6 1.2.6 TheEgyptianSocietyofToxicology 7 1.2.7 TheAfricaEducationInitiative(NEF) 8 1.2.8 EnvironmentalProtectionAgency—PrograminAfrica 8 1.3 InteractionsBetweenAfricanSocietiesofToxicological ScienceswithEuropeanandAmericanSocieties 11 1.3.1 InternationalUnionofToxicology 11 1.3.2 GeneralObjectivesofIUTOX 11 1.3.3 TheSocietyofToxicology 11 1.4 TheRoleofAfricanSocietiesofToxicologicalSciences inGovernmentPolicyMaking 12 1.5 InformationResourcesinToxicology 13 1.5.1 ToxicRemnantsofWar 13 1.6 ConclusionsandRecommendations 14 References 14 2 EthicalIssuesforAnimalUseinToxicological ResearchinAfrica 17 WafaaElSayedAbdEl-Aal 2.1 Introduction 17 2.2 Definitions 18 2.3 EthicalAspectsofMedicinalPlantsinAfrica 20 2.4 TheImportanceofAnimalsinToxicologicalStudies 21 vi Contents 2.5 GuidelinesofAnimalResearchEthics 22 2.5.1 History:DevelopmentofGuidelines andLegalFrameworks 22 2.5.2 3Rs(Reduction,Replacement,andRefinement) 23 2.5.3 InternationalGuidelinesforUseandCareofAnimals inScientificProcedures 25 2.5.4 GuidelinesforManagingandSupervisingBreeding andHoldingFacilities 25 2.5.5 HazardsforAnimalCarePersonnel 26 2.5.6 TrainingGuidelines 26 2.6 AnimalWelfareIssues 27 2.6.1 WhatIsAnimalWell-BeingorWelfare? 27 2.6.2 StrategiestoSafeguardAnimalWell-being, AustralianCode,2013[15] 27 2.6.3 SomePossibleWaysofProtectingtheWelfareofAnimals UsedinResearchorTeaching 28 2.6.4 ProtectionofAnimalsDuringTransport andRelatedOperations 28 2.6.5 AcclimatizationandConditioning 29 2.6.6 FoodandWater 29 2.6.7 AvoidingorMinimizingDiscomfort,Anxiety,andPain 29 2.6.8 AnesthesiaandAnalgesia 29 2.6.9 Euthanasia 30 2.7 InstitutionalAnimalCareandUseCommittees 30 2.7.1 ResponsibilitiesofAECs,AustralianCode,2013[15] 31 2.7.2 InstitutionalAnimalCareandUseCommittees MonitoringSystem,Accordingtothe AustralianCode,2013[15] 31 2.7.3 InstitutionalAnimalCareandUseCommitteesRecords, AccordingtotheNACLAR,2004[36] 31 2.7.4 ResponsibilitiesoftheInstitutionsRegarding AnimalResearch,According totheNACLAR,2004[36] 32 2.7.5 IACUCsinDevelopedCountries 32 2.7.6 EthicalReview 33 2.7.7 PrinciplesofEthicalReview,According toFry,2012[27] 33 2.8 HealthResearchEthicsinAfrica 34 2.9 ChallengesofResearchEthicsinAfrica 36 2.10 LawsofAnimalResearchEthicsinAfrica 36 2.10.1 SituationinSomeAfricanCountries 36 2.11 Conclusions 37 Acknowledgments 38 References 38 Contents vii 3 Critical ReviewoftheGuidelinesandMethods inToxicologicalResearchinAfrica 43 LouisL.GadagaandDexterTagwireyi 3.1 Introduction 43 3.2 NeedforToxicityTesting 44 3.3 AcuteToxicityTesting 46 3.4 AlternativesMethodsfortheOralLD Test 46 50 3.4.1 RepeatedDoseToxicityTesting 46 3.4.2 SubacuteStudies 47 3.4.3 SubchronicStudies 47 3.4.4 ChronicStudies 47 3.4.5 GenotoxicityandMutagenicityTesting 47 3.4.6 ClinicalTestingStudies 48 3.5 Conclusion 49 References 49 4 DiscordantResultsinPlantToxicityStudiesinAfrica: AttemptofStandardization 53 RolandE.Akhigbe 4.1 Introduction 53 4.2 ToxicologicalEvaluation:ParametersandInterpretation 53 4.2.1 BodyandOrganWeight 54 4.2.2 HematologicalProfile 54 4.2.3 PlasmaEnzymeActivities 55 4.2.4 HepaticandRenalFunctionTests 56 4.2.5 OxidativeStress 56 4.2.6 GastrointestinalandNeurologicalManifestations 57 4.3 StandardValuesforParametersinToxicologicalSurvey 57 4.4 Conclusion 57 References 59 5 AcuteandSubacuteToxicitiesofAfrican MedicinalPlants 63 GeraldNgoTekeandVictorKuete 5.1 Introduction 63 5.2 TheAcuteandSubacuteEffectsofMedicinalPlants 64 5.2.1 LeafPoisoning 64 5.2.2 Flowersand/orFruits 65 5.2.3 StemBark 66 5.2.4 Roots 66 5.3 ExperimentalModelsforToxicologicalStudies 66 5.3.1 AnimalsUsedinAcuteandSubacuteToxicitySurveys 67 5.3.2 AnimalsUsedinAcuteToxicity 67 5.3.3 AnimalsUsedinSubacuteToxicity 68 5.3.4 MethodsinAcuteandSubacuteToxicitySurvey 68 viii Contents 5.4 TheSignificanceofLD inAcuteToxicityScreenings 71 50 5.4.1 HistoryofLD Determination 71 50 5.4.2 SignificanceofLD inToxicityStudies 71 50 5.4.3 ToxicSymptomsinAcuteandSubacute ToxicityStudies 72 5.5 LimitationsoftheStudyoftheAcuteand SubacuteToxicitiesofMedicinalPlants 73 5.6 AfricanPlantsScreenedforTheirAcute andSubacuteToxicities 74 5.7 Conclusion 74 References 87 6 SubchronicandChronicToxicitiesofAfricanMedicinalPlants 99 AdejuwonAdewaleAdeneye 6.1 Introduction 99 6.2 SubchronicandChronicToxicityEffect ofMedicinalPlants 101 6.2.1 Hypericumperforatum(Hypericaceae) 101 6.2.2 RosmarinusofficinalisLinn.(Lamiaceae) 102 6.2.3 Erythrinamulungu(Fabaceae) 102 6.2.4 Hydrastiscanadensis(Ranunculaceae) 103 6.2.5 Symphytumofficinale(Bignoniaceae) 103 6.2.6 Ginkgobiloba(Ginkgoaceae) 103 6.2.7 PipermethysticumForsterf.(Piperaceae) 104 6.2.8 Glycyrrhizaglabra(Fabaceae) 105 6.3 Methods,Parameters,andDataInterpretationinSubchronic andChronicToxicityScreeningsWorldwideandinAfrica 106 6.3.1 ConventionalSubchronicandChronicOralTests 106 6.3.2 OECDRecommendationsforSubchronic andChronicToxicityStudy 108 6.3.3 WHORecommendationsforSubchronic andChronicToxicityStudy 113 6.3.4 OtherRecommendations 115 6.4 AnimalsUsedinSubchronicandChronic ToxicityScreenings 116 6.5 ObservableSymptomsandSignsinSubchronicandChronic ToxicityScreenings 117 6.6 LimitationsoftheStudyoftheSubchronicandChronicToxicity ofMedicinalPlants 117 6.7 AfricanPlantsScreenedforTheirSubchronicandChronicToxicity 118 6.7.1 SphenocentrumjollyanumPierre(Menispermaceae) 118 6.7.2 SpathodeacampanulataP.Beauv(Bignoniaseae) 119 6.7.3 Syzigiumaromaticum(L.)Merr.andPerry(Myrtaceae) 119 6.7.4 Hunteriaumbellata(K.Schum.)Hallierf.(Apocynaceae) 120 6.7.5 Cnestisferruginea(CF)VahlexDC(Connaraceae) 121 Contents ix 6.7.6 CorrigiolatelephiifoliaPourr.(Caryophyllaceae) 121 6.7.7 CaricapapayaLinn.(Caricaceae) 122 6.7.8 AlliumcepaLinn.(Liliaceae) 122 6.7.9 AlliumsativumLinn.(Liliaceae) 123 6.7.10 CarumcarviLinn.(Apiaceae/Umbellifereae) 124 6.7.11 NigellasativaLinn.(Ranunculaceae) 124 6.7.12 ViscumalbumL.(Santalaceae) 125 6.8 Conclusion 125 References 126 7 ToxicPlantsUsedinAfricanTraditionalMedicine 135 Jean-de-DieuTamokouandVictorKuete 7.1 Introduction 135 7.2 ToxicSymptomsofMedicinalPlants 136 7.2.1 GastrointestinalTract Symptoms 137 7.2.2 LiverSymptoms 138 7.2.3 SkinandEyeSymptoms 138 7.2.4 BloodandCardiovascularSystem 139 7.2.5 NervousSystemSymptoms 140 7.2.6 ReproductiveandDevelopmentalEffects 141 7.2.7 KidneyandBladderSymptoms 143 7.3 ToxicityofAfricanMedicinalPlants 144 7.4 ToxicAfricanMedicinal PlantsasIdentified byTheirMediumLethalDoses(LD )Values 50 andInducedPhysicalSymptoms 146 7.5 ToxicAfricanMedicinal PlantsasIdentified byBiochemicalIndices 165 7.6 Conclusion 170 References 171 8 CytotoxicityofAfricanMedicinalPlantsAgainst NormalAnimalandHumanCells 181 LyndyJ.McGaw,EsameldinE.Elgorashi andJacobusN.Eloff 8.1 Introduction 181 8.1.1 ImportantFactorstoConsiderinCytotoxicity Experiments 182 8.2 NecessityforCytotoxicityTesting 183 8.3 LimitationsofCytotoxicityTesting 184 8.4 DifferentTypesofCytotoxicityAssay 185 8.4.1 MetabolismReductaseViabilityAssays 186 8.4.2 BioluminescentATPAssays 187 8.4.3 EnzymeRelease-BasedCytotoxicityAssays 187 8.4.4 OtherCommonlyUsedAssays 188 8.4.5 BrineShrimpAssay 188