RESEARCH ARTICLE Open Access Medicinal properties of true cinnamon Cinnamomum zeylanicum - PDF document

RESEARCHARTICLEOpenAccess Medicinalpropertiesof ‘ true ’ cinnamon ( Cinnamomumzeylanicum ):asystematicreview PriyangaRanasinghe 1* ,ShehaniPigera 1 ,GASirimalPremakumara 2 ,PriyadarshaniGalappaththy 1 , GodwinRConstantine 3 andPrasadKatulanda 3 Abstract Background: IntraditionalmedicineCinnamonisconsideredaremedyforrespiratory,digestiveand gynaecologicalailments. In-vitro and in-vivo studiesfromdifferentpartsoftheworldhavedemonstratednumerous beneficialmedicinaleffectsof Cinnamomumzeylanicum (CZ).Thispaperaimstosystematicallyreviewthescientific literatureandprovideacomprehensivesummaryonthepotentialmedicinalbenefitsofCZ. Methods: Acomprehensivesystematicreviewwasconductedinthefollowingdatabases;PubMed,WebofScience, SciVerseScopusforstudiespublishedbefore31stDecember2012.Thefollowingkeywordswereused: “ Cinnamomumzeylanicum ” , “ Ceyloncinnamon ” , “ Truecinnamon ” and “ SriLankancinnamon ” .Toobtainadditional dataamanualsearchwasperformedusingthereferencelistsofincludedarticles. Results: WebofScience=76andSciVerseScopus=591.Thirteenadditionalarticleswereidentifiedbysearchingreference lists.Afterremovingduplicatesthetotalnumberofarticlesincludedinthepresentreviewis70.Thebeneficial healtheffectsofCZidentifiedwere;a)anti-microbialandanti-parasiticactivity,b)loweringofbloodglucose,blood pressureandserumcholesterol,c)anti-oxidantandfree-radicalscavengingproperties,d)inhibitionoftau aggregationandfilamentformation(hallmarksofAlzheimer ’ sdisease),e)inhibitoryeffectsonosteoclastogenesis, f)anti-secretagogueandanti-gastriculcereffects,g)anti-nociceptiveandanti-inflammatoryactivity,h)wound healingpropertiesandi)hepato-protectiveeffects.Thestudiesreportedminimaltoxicandadverseeffects. Conclusions: Theavailable in-vitro and in-vivo evidencesuggeststhatCZhasmanybeneficialhealtheffects. However,sincedataonhumansaresparse,randomizedcontrolledtrialsinhumanswillbenecessarytodetermine whethertheseeffectshavepublichealthimplications. Keywords: Cinnamomumzeylanicum ,Truecinnamon,Ceyloncinnamon,Medicinalproperties,Healthbenefits Background Cinnamonisacommonspiceusedbydifferentcultures aroundtheworldforseveralcenturies.Itisobtainedfrom theinnerbarkoftreesfromthegenusCinnamomum,a tropicalevergreenplantthathastwomainvarieties; Cinnamomumzeylanicum (CZ)andCinnamoncassia (CC)(alsoknownas Cinnamomumaromaticum/ Chinese cinnamon).Inadditiontoitsculinaryuses,innativeAyur- spiratory,digestiveandgynaecologicalailments.Almost everypartofthecinnamontreeincludingthebark,leaves, flowers,fruitsandroots,hassomemedicinalorculinary use.Thevolatileoilsobtainedfromthebark,leaf,androot barksvarysignificantlyinchemicalcomposition,which suggeststhattheymightvaryintheirpharmacologicalef- fectsaswell[1].Thedifferentpartsoftheplantpossess thesamearrayofhydrocarbonsinvaryingproportions, withprimaryconstituentssuchas;cinnamaldehyde(bark), eugenol(leaf)andcamphor(root)[2].Thuscinnamonof- fersanarrayofdifferentoilswithdiversecharacteristics, eachofwhichdeterminesits ’ valuetothedifferentindus- tries.Forexampletherootwhichhascamphorasthe mainconstitute,hasminimalcommercialvalueunlikethe leafandbark[3].Itisthischemicaldiversitythatislikely *Correspondence: priyanga.ranasinghe@gmail.com 1 DepartmentofPharmacology,FacultyofMedicine,UniversityofColombo, Colombo,SriLanka ©2013Ranasingheetal.;licenseeBioMedCentralLtd.Thisisanopenaccessarticledistributedunderthetermsofthe CreativeCommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse, distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Ranasinghe etal.BMCComplementaryandAlternativeMedicine 2013, 13 :275 http://www.biomedcentral.com/1472-6882/13/275 tobethereasonforthewide-varietyofmedicinalbenefitsobservedwithcinnamon.CZ,alsoknownasCeyloncinnamon(thesourceofitsLatinname,zeylanicum)ortruecinnamonisindigen-oustoSriLankaandsouthernpartsofIndia[3].ThreeofthemaincomponentsoftheessentialoilsobtainedfromthebarkofCZaretrans-cinnamaldehyde,eugenol,andlinalool,whichrepresent82.5%ofthetotalcompos-ition[4].Trans-cinnamaldehyde,accountsforapproxi-mately49.962.8%ofthetotalamountofbarkoil[5,6].Cinnamaldehydeandeugenolarealsothemajorcompo-nentsofCZextracts[7].Abriefcomparisonofthetwomainvarietiesofcinnamon(CZandCC)isincludedasaAdditionalfile1.OneimportantdifferencebetweenCCandCZistheircoumarin(1,2-benzopyrone)content[8].ThelevelsofcoumarinsinCCappeartobeveryhighandposehealthrisksifconsumedregularlyinhigherquantities.AccordingtotheGermanFederalInstituteforRiskAssessment(BfR),1kgofCC(CC)powdercontainsapproximately2.1-4.4gofcoumarin,whichmeans1teaspoonofCCpowderwouldcontainaround5.8-12.1mgofcoumarin[9].ThisisabovetheTolerableDailyIntake(TDI)forcoumarinof0.1mg/kgbodyweight/dayrecommendedbytheEuropeanFoodSafetyAuthority(EFSA)[10].TheBfRinitsreportspecificallystatesthatCZcontainshardlyanycoumarin[9].Coumarinsaresecondaryphyto-chemicalswithstronganticoagulant,carcinogenicandhepato-toxicproperties[10].Theunderlyingmechanismsforthecoumarin-relatedtoxiceffectsareyettobecompletelyelucidated[10].DuetothehighconcentrationsinCC(comparedwithotherfoods),despitetherelativelylowamountsoftheconsump-tionofspices,studieshaveshownthancoumarinexposurefromfoodconsumptionismainlyduetoCC[10].TheEFSAadvocatesagainsttheregular,longtermuseofCCasasupplementduetoitscoumarincontent[11].Inaddition,accordingtocurrentlyavailableevidencecouma-rindoesnotseemtoplayadirectroleintheobservedbio-logicaleffectsofCC.Hence,althoughCChasalsoshownmanybeneficialmedicinalproperties,itscoumarincon-tentislikelytobeanobstacleagainstregularuseasapharmaceuticalagent,unlikeinthecaseofCZ.In-vitroin-vivostudiesinanimalsandhumansfromdifferentpartsoftheworldhavedemonstratednumerousbeneficialhealtheffectsofCZ,suchasanti-inflammatoryproperties,anti-microbialactivity,redu-cingcardiovasculardisease,boostingcognitivefunctionandreducingriskofcoloniccancer[12].ThispaperaimstosystematicallyreviewthescientificliteratureandprovideacomprehensivesummaryonthepotentialmedicinalbenefitsofTrueCinnamonCinnamomumzeylanicum).Wealsoaimtoprovideascientificguidetoresearchersonthepotentialareasforfutureresearchbasedonthepositivefindingsobtainedthusfarfromstudiesconductedbyvariousresearchteamsfromaroundtheworld.Asystematicreviewofpublishedstudiesreportingtheme-dicinaleffectsofCZwasundertakeninaccordancewiththePRISMA(PreferredReportingItemsforSystematicre-viewsandMeta-Analyses)statementguidelines(Additionalfile2)[13].Acomprehensivesearchoftheliteraturewasconductedinthefollowingdatabases;PubMed®(U.S.NationalLibraryofMedicine,USA),WebofScience®[v.5.3](ThomsonReuters,USA),SciVerseScopus®(ElsevierPropertiesS.A,USA)forstudiespublishedbe-fore31December2012.Weusedthefollowingmed-icalsubjectheadingsandkeywords:CinnamomumzeylanicumCeyloncinnamonTruecinnamonSriLankancinnamon.ResultswerelimitedtostudiesinEnglish,whileconferenceproceedingsandcommen-tarieswereexcluded.Inthesecondstagethetotalhitsobtainedfromsearchingthedatabasesusingtheabovesearchcriteriawaspooledtogetherandduplicatearticleswerere-moved.Theremainingarticleswereinitiallyscreenedbyreadingtheandthereaftertheabstracts.Studiesnotsatisfyingtheinclusioncriteriawereexcludedatthesestages.Theremainingarticleswerescreenedinthefinalstagebyreadingthefull-textandthosenotmeetinginclusioncriteriawereexcluded.Toobtainadditionaldataamanualsearchwasperformedusingthereferencelistsofincludedarticles.Whereverpossibleforwardcita-tionsofthestudiesretrievedduringtheliteraturesearchwastracedandscreenedforpossibleinclusion.Thissearchprocesswasconductedindependentlybytwore-viewers(PRandSP)andthefinalgroupofarticlestobeincludedinthereviewwasdeterminedafteraniterativeconsensusprocess.LiteraturesearchTheliteraturesearchusingtheabovesearchcriteriaidentifiedthefollowingnumberofarticlesinthere-spectivedatabases;PubMed®(n=54),WebofScience®(n=76)andSciVerseScopus®(n=591).Thirteenadd-itionalarticleswereidentifiedbymanuallysearchingthereferencelistsandforwardcitationsofincludedpapers.Afterremovingduplicatesthetotalnumberofarticlesincludedinthepresentreviewis70.ThesearchstrategyissummarizedinFigure1.In-vitroandin-vivoanti-microbialpropertiesTherewere30differentstudiesevaluatingthein-vitroanti-microbialpropertiesofCZ.Table1summarizesthefindingsofthesestudies.AccordinglyCZhasshownpo-tentialanti-microbialactionagainstawidevarietyofRanasingheetal.BMCComplementaryandAlternativeMedicine:275Page2of10http://www.biomedcentral.com/1472-6882/13/275 bacteria (Acinetobacterbaumannii,Acinetobacterlwoffii, Bacilluscereus,Bacilluscoaguiaris,Bacillussubtilis, Brucellamelitensis,Clostridiumdifficile,Clostridium perfringens,Enterobacteraerogenes,Enterobactercloacae, Enterococcusfaecalis,Enterococcusfaecium,Escherichia coli,HaemophilusInfluenza,Helicobacterpylori,Klebsiella pneumonia,Listeriaivanovii,Listeriamonocytogenes, Mycobacteriumsmegmatis,Mycobacteriumtuberculosis, Proteusmirabilis,Pseudomonasaeruginosa,Saccharomy- cescerevisiae,Salmonellatyphi,Salmonellatyphimurium, Staphylococcusalbus,Staphylococcusaureus,Streptococcus agalactiae,Streptococcuspneumoniae,Streptococcus pyogenesandYersiniaenterocolitica). Inadditionthere seemstobeactivityagainstnumerousfungi( Aspergillus fiavus,Aspergillusfumigatus. Aspergillusnididans,Aspergillusniger,Aspergillus ochraceus,Aspergillusparasiticus,Aspergillusterreus, Candidaalbicans,Candidagl abrata,Candidakrusei, Candidaparapsilosis,Candidatropicalis,Crytococcus neoformans,Epidermophytonfloccosum,Hisioplasma capsulatum,Malasseziafurfur,Microsporumaudouini, MicrosporumcanisMicrosporumgypseum,Trichophyton mentagraphytes,TrichophytonrubrumandTrichophyton tonsurans). CZhasalsodemonstratedactivityagainst thehumanrota-virus(Table1). Therewere5studiesevaluating in-vivo anti-microbial propertiesinanimals.Abu,etal.[44]investigatedtheef- fectofadministrationCZoilonthedevelopmentand progressionoftheexperimentalcryptosporidiosisin mice,andtheyshowedthatadministrationofCZoil wasbeneficialinprotectingsusceptiblehostsagainstop- portunisticzoonoticparasitessuchas Cryptosporidium parvum .Rosti,etal.[45,46]reportedtwocasesofin- fantswhowerechroniccarriersof Salmonellaenteritidis whoreceivedshortterm(10days)administrationof groundedCZbarkwhichledtoconsistentlynegative stoolculturesandnoclinicalormicrobiologicalrelapses. ActivityofCZagainstfluconazoleresistantandsuscep- tiblecandidawerestudiedinHIVinfectedpatientshav- ingpseudo-membranousCandida,where3patientsout of5showedimprovementsintheiroralcandidiasis[47]. Theeffectsofsugaredchewinggumcontainingcinnamic aldehydeandnaturalflavoursfromCZontheshort-term germ-killingeffectontotalandH 2 S-producingsalivary anaerobeswasinvestigatedbyZhu,etal.[48].Significant reductionsintotalsalivaryanaerobesandH 2 S-producing salivaryanaerobeswereobserved20minutesaftersubjects chewedthegum. In-vitroandin-vivoanti-parasiticeffects Samarasekera,etal.[49]investigatedthemosquitocontrol propertiesofessentialoilsofleafandbarkofCZagainst Culex quinquefasciatus ,Anopheles tessellatus and Aedes aegypti .CZbarkoilshowedgoodknock-downand mortalityagainst A.tessellatus (LD 50 0.33
g/mL)and C. quinquefasciatus (LD 50 0.66
g/mL)thanleafoil(LD 50 Figure1 Summarizedsearchstrategy. Ranasinghe etal.BMCComplementaryandAlternativeMedicine 2013, 13 :275Page3of10 http://www.biomedcentral.com/1472-6882/13/275 Table1Anti-microbialpropertiesofCinnamomumzeylanicumAuthor[ref]Organism(s)testedMainoutcomesAgasthyaAS,etal.[Escherichiacoli,Salmonellatyphi,SalmonellaparatyphiA/B,BrucellaabortusandBrucellamelitensisCZextractwereactiveonlyagainstBrucellamelitensisBaratthaMT,etal.[Clostridiumperfringens,E.coli,Klebsiellapneumonia,Pseudomonasaeruginosa,S.aureus,StreptococcusfaecalisandYersiniaenterocoliticaVolatileoilsfromCZhadsignificantactivityagainstthegrowthoffoodpoisoningorganisms,foodspoilageorganismsandorganismsoffaecaloriginUK,Italy,PortugalBayoubK,etal.[Listeriamonocytogenes,S.aurus,E.coli,Enterococcusfaecalis,Klebsiellapneumoniae,Enterobactercloacae,AcinetobacterbaumanniiCZextractsdemonstratedsignificantinhibitoryeffectsS.aureusEnterobactercloacae,AcinetobacterbaumanniiandListeriamonocytogenes(MIC0.4mg/ml)BhatiaM,etal.[CandidaalbicansAmongallspicestestedCZinhibitedC.albicanseffectively(MIC7.81CarmoES,etal.[]Aspergillusspecies(A.fumigatus,A.niger,A.flavus,A.parasiticus,A.terreusandA.ochraceusCZessentialoilpossessesstronganti-aspergillusactivityinhibitingthegrowth,sporegerminationandcausingdeleteriouscellularmorphologicalchangesDubeyRC,etal.[Salmonellatyphi,Staphylococcusaureus,Escherichiacoli,KlebsiellapneumoniaeandBacillussubtilisCZessentialoilsinhibitedgrowthofallorganisms.Gram-negativeorganismsweremoresusceptiblethangram-positiveones.ElumalaiS,etal.[Bacillussubtilis,Klebsiellapneumonia,Pseudomonasaeruginosa,StaphylococcusaureusandEscherichiacoliPercentageinhibitionwithCZwas;B.Subtilis(40.0%)Klebsiellapneumonia,Pseudomonasaeruginosa(45.0%),Staphylococcusaureus(37.8%)andEscherichiacoli(40.0%).InhibitionactivityofC.CassiagreaterthanCZ.FabioA,etal.[S.pyogenes,S.agalactiae,S.pneumonia,Klebsiellapneumoniae,H.InfluenzaandS.aureusOfthe13essentialoilsevaluatedCZandthymeshowedthehighestactivityinhibitingallthestrainsstudiedFerhoutH,etal.[MalasseziafurfurandCandidaalbicansOfthe3oilsstudiedCZoilexhibitedthestrongestactivitytowardsthetwoyeasts.M.furfurshowedagreatersensitivitytoCZGonçalvesJLS,etal.[]Humanrota-virusCZleavesandbarkwasabletoinhibitthepropagationofhumanrotavirus32.4%and33.9%respectively.GuerraFQS,etal.[]Acinetobacterspp.CZessentialoilssuppressesthegrowthofAcinetobacterspp.andasynergisticeffectwasobservedwhencombinedwithantibioticsHosseininejadZ,etal.[HelicobacterpyloriCZexhibitedthemostinhibitoryeffectonH.pyloriessentialoilsofCZwithIC=0.3l/mlcompletelyinhibitedthegrowthofH.pyloriJantanIB,etal.[Trichophytonmentagrophytes,T.tonsurans,T.rubrum,Microsporumcanis,M.gypseum,M.audouini,Aspergillusfumigates,Candidaalbicans,C.glabrata,C.parapsilosis,C.tropicalisandCrytococcusneoformansAmongalltheessentialoils,theleafandbarkoilsofCZshowedthehighestactivityagainstallthefungiwithMICvaluesof0.04to0.63JirovetzL,etal.[PseudomonasfluorescensEscherichiacolitaphylococcusaureusCZessentialoilswereactiveagainstE.coliandS.aureusP.fluorescenswasresistant.Austria,CameroonKhanR,etal.[]Multidrugresistant(MDR)strainsofEscherichiacoli,KlebsiellapneumoniaeandCandidaalbicans.TheMDRstrainsweresensitivetotheantimicrobialactivityofCZ.LimaEO,etal.[Trichophytonrubrum,T.mentagraphytes,MicrosporumcanisandEpidermophytonfloccosumCZinhibited80%ofthedermatophytestrainstestedandproducedinhibitionzonesmorethan10mmindiameterMaidmentC,etal.[EscherichiacoliB,staphylococcusalbusandSaccharomycescerevisiaeCZdemonstratedmicrobialinhibitoryeffect;alcoholicextractshadgreateractivitythanaqueousextracts.Essentialoilshadgreateractivitythanthespices.MICsweresmallerwiththeoilsthanwiththespices.MandalS,etal.[]MethicillinresistantStaphylococcusaureusCZandC.aromaticumshowedthestrongestinvitroantibacterialactivityagainstMethicillinResistantS.aureusMasturaM,etal.[Trichophytonmentagrophytes,T.rubrum,Microsporumcanis,CandidaalbicansandC.glabrataCZwasamoderateinhibitorofallthefungitested(MICvalues1.26Ranasingheetal.BMCComplementaryandAlternativeMedicine:275Page4of10http://www.biomedcentral.com/1472-6882/13/275 1.03and2.1g/mL).Yang,etal.[50]showedthatCZbarkessentialoilwasslightlylesseffectivethaneitherd-phenothrinorpyrethrumagainsteggsandadultfemalesofhumanheadlouse,Pediculushumanuscapitis,usingdirectcontactandvapourphasetoxicitybioassays.In-vitroandin-vivoeffectsonbloodpressure,glycaemiccontrolandlipidsArecentmeta-analysisbyRanasinghe,etal.andasystem-aticreviewbyBandaraetal.,ontheeffectsofCZextractsondiabetesdemonstratesnumerousbeneficialeffectsbothin-vitroandin-vivo[51,52].In-vitroCZhasdemonstratedapotentialfor;a)reducingpost-prandialintestinalglucoseabsorptionbyinhibitingtheactivityofenzymesinvolvedincarbohydratemetabolism(pancreaticamylaseandglucosidase),b)stimulatingcellularglucoseuptakebymembranetranslocationofGLUT-4,c)stimulatingglu-cosemetabolismandglycogensynthesis,d)inhibitinggluconeogenesisbyeffectsonkeyregulatoryenzymesandf)stimulatinginsulinreleaseandpotentiatinginsulinreceptoractivity[51].CinnamtanninB1wasidentifiedasthepotentialactivecompoundresponsiblefortheseeffects[51].ThebeneficialeffectsofCZIn-vivoincludes;a)attenuationofweightlossassociatedwithdiabetes,b)reductionofFastingBloodGlucose,c)reducingLDLandincreasingHDLcholesterol,d)reducingHbA1cande)increasingcirculatinginsulinlevels[51].InadditionCZalsoshowedbeneficialeffectsagainstdiabeticneuropathyandnephropathy[51].Hasanetal.[53],alsoconfirmedtheseeffectsanddem-onstratedthatCZreducedtotalcholesterol,LDLcholes-terolandtriglycerideswhileincreasingHDL-cholesterolindiabeticrats.Similarresultshavealsobeenobservedinhyper-lipidaemicalbinorabbits[54].However,feedingCZtoanimalsatlevelscorrespondingtotheaveragehu-mandietaryintakehasnotshowntoreducelipidlevelssignificantly[55].Nyadjeuetal.[56]examinedtheeffectsofCZextracts(CZA)onmeanarterialbloodpressure(BP)ofnormotensive(NR)rats,salt-loadedhypertensiverats(SLHR),L-NAMEhypertensiverats(LNHR)and Table1Anti-microbialpropertiesofCinnamomumzeylanicumMeadesJ,Jretal.[Escherichiacoli(acetyl-CoAcarboxylaseinhibition)CZinhibitedthecarboxyl-transferasecomponentofE.coliacetyl-CoAcarboxylaseenzyme.USA,UK,SouthAfricaMishraAK,etal.[E.coli,Klebsiellapneumonia,Proteusvulgaris,Pseudomonasspp.,S.aureusandS.pneumoniaOfthe3essentialoilsevaluatedCZoilshowedthestrongestinhibitoryactivityagainstallmicro-organismstested.NegiPS,etal.[Bacilluscereus,B.coaguiaris,B.subtilis,S.aureus,E.coliandPseudomonasaeruginosaAllcrudeextractsofCZfruitsshowedantibacterialactivity.Ethylacetateandbenzeneextractsshowedhigheractivitythanmethanolandwaterextract.India,USANoudehGD,etal.[S.aureus,Bacillussubtilis,E.coliandPseudomonasaeruginosaCZinhibitedthegrowthofalltestedGram-positiveandGram-negativestrains.Iran,UKRanaIS,etal.[Pseudomonasaeruginosa,S.aureus,SalmonellatyphimuriumandBacillussubtilisOfthe19essentialoilsevaluatedthehighestantibacterialactivitywasdepictedbyCZagainstallbacteriaSenhajiO,etal.[E.coliO157:H7Inthepresenceof0.05%oftheoil,mostofcellswerekilledafter30min,suggestingabactericidalactionagainstE.coli.TheMICwasaround625ppm.ShahverdiAR,etal.[ClostridiumdifficileTheessentialoilofCZbarkenhancedthebactericidalactivityofclindamycinanddecreasedtheMICofclindamycinforC.difficile.SinghHB,etal.[Aspergillusniger.A.fumigatus.A.nididans,A.fiavus,Candidaalbicans,C,tropicalis,C,pseudotropicalisandHisioplasmacapsulatumVapoursofCZbarkoilandcinnamicaldehydeareeffectivelytoxicatverylowdosesandathighinoculumdensityagainstthetestfungicausingrespiratorytractmycosesSivakumarA,etal.[MycobacteriumtuberculosisWater(MIC-100g/ml)andethanolic(MIC-200extractsofCZwasobservedtohaveactivityagainstM.tuberculosisTekwuE,etal.[MycobacteriumtuberculosisstrainsH37RvandH37RaTheMICforH37RaandH37Rvstrainswere1024and512g/mlrespectivelyandMBCwas�2048forbothstrains.Cameroon,TurkeyUnlu,Metal.[S.aureus,Streptococcuspyogenes,S.pneumonia,Enterococcusfaecalis,Enterococcusfaecium,Bacilluscereus,Acinetobacterlwoffii,Enterobacteraerogenes,E.coli,Klebsiellapneumoniae,Proteusmirabilis,Pseudomonasaeruginosa,Salmonellatyphimurium,Clostridiumperfringens,Listeriamonocytogenes,Listeriaivanovii,Mycobacteriumsmegmatis,Candidaalbicans,CandidaparapsilosisandCandidakruseiTheessentialoilofCZshowedstrongantimicrobialactivityagainstallmicroorganismstested,Ranasingheetal.BMCComplementaryandAlternativeMedicine:275Page5of10http://www.biomedcentral.com/1472-6882/13/275 spontaneouslyhypertensiverats(SHR).ImmediatelyafterintravenousadministrationasignificantdropofBPwasshowninNTR,SLHRandLNHRinadosedependentmanner,thedropinBPwasnotdosedependentinSHR[56].Wansi,etal.demonstratedsimilareffectsinNTRandSLHR,theyalsoshowedthatCZhasavaso-relaxanteffectontheratthoracicaorticringsegments,suggestingthat,CZmightbeinhibitingextracellularCaL-typevoltage-sensitivechannels[57].Markey,etal.[58]testedthehypothesisthatsupplementingasinglehighfructosebreakfastwith3gofcinnamonwoulddelaygas-tricemptyingofahigh-fatsolidmealutilizingtheoctanoicacidbreathtest,andconsequentlyreducepost-prandialbloodglucoseandlipidconcentrations.Thereconcludedthatcinnamondidnotchangegastricemptyingparameters,postprandialtriacylglycerolorglucosecon-centrationsafterasingleadministration[58].Itisimport-anttonotethatallin-vivostudiesexcepttheabovestudywereconductedinanimals.In-vitroandin-vivoanti-oxidantpropertiesTheessentialoilsobtainedfromthebarkofCZandeugenolhasshownverypowerfulactivities,decreasing3-nitrotyrosineformationandinhibitingtheperoxynitrite-inducedlipidperoxidationinin-vitroassays[59].ThevolatileoilsofCZhasshown55.9%and66.9%antioxidantactivityat100and200ppmconcentration,respectively[60].ThedriedfruitextractsofCZwithethylacetate,acetone,methanolandwaterexhibitedantioxidantactivityintheorderofwater�methanol�acetone�ethylacetate[61].Theetheric(0.69mg),methanolic(0.88mg)andaqueous(0.44mg)cinnamonextracts,inhibitedtheoxida-tiveprocessin68%,95.5%and87.5%respectively[62].A.Kitazuru,etal.[63]studiedtheeffectsofionizingradiationonnaturalCZantioxidantsandshowedthatirradiationinthedoserangeapplieddidnothaveanyeffectontheanti-oxidantpotentialofthecinnamoncompounds.CZbarkextractswerefoundtobepotentinfreerad-icalscavengingactivityespeciallyagainstDPPHradicalsandABTSradicalcations,whilethehydroxylandsuper-oxideradicalswerealsoscavengedbythetestedcom-pounds[64].SimilarfindingswerenotedbyPrakash,etal.whoshowedthatCZhas65.3%ofanti-oxidantac-tivityandstrongfreeradicalscavengingactivity[65].Ranjbar,etal.[66]treated18operatingroompersonnelwithCZ(100mg/300mLtea)dailyfor10daysandbloodsampleswereanalyzedforbiomarkersofoxidativestressbiomarkersincludingLipidPeroxidationLevel(LPO),TotalAntioxidantPower(TAP)andTotalThiolMolecules(TTM).TreatmentofsubjectswithcinnamoninducedasignificantreductioninplasmaLPO,howevernostatisticallysignificantalterationwasfoundforplasmaTAPandTTMafter10daystreatmentwithCZ[66].Treatmentof54healthyvolunteerswithCZ100mg/30mlofteadailyweresignificantlyeffectiveinthereductionoflipidperoxidationandincreasingTAPandTTMincom-parisonwithcontrols[67].TheextentofincreaseinplasmaTBARSandTAPfortheCZgroupwassignificantlyhigherthaninthosegiveregularteaonly[67].Otherin-vitroeffectsAnaqueousextractofCZisknowntoinhibittauaggre-gationandfilamentformation,whicharehallmarksofAlzheimersdisease[68].Theextractalsopromotescompletedisassemblyofrecombinanttaufilamentsandcausesubstantialalterationofthemorphologyofpaired-helicalfilamentsisolatedfrombrainsofthosewithAlzheimersdisease,howeveritwasnotdeleterioustothenormalcellularfunctionoftau.AnA-linkedproantho-cyanidintrimermoleculeisolatedfromtheCZextracthasshowntocontainasignificantproportionofthisinhibitoryactivity[68].Takasao,etal.[69]demonstratedthatCZextractsfacilitatescollagenbiosynthesisinhumandermalfibroblasts.CZextractup-regulatedbothmRNAandproteinexpressionlevelsoftypeIcollagenwithoutcyto-toxicity,cinnamaldehydewasthemajoractivecompo-nentpromotingtheexpressionofcollagenbyHPLCandNMRanalysis.ThissuggeststhatCZextractsmightbeusefulinanti-agingtreatmentofskin[69].CZextractshavealsoexhibitedthestronginhibitoryeffectsonosteoclastogenesis[70].CZdose-dependentlyinhibitedosteoclast-likecellformationatconcentrationsof12.5-g/mlwithoutaffectingcellviability.Thisfindingraisesprospectsforthedevelopmentofanovelapproachinthetreatmentofosteopenicdiseases[70].Otherin-vivoeffectsinanimalsCZisknowntohaveanti-secretagogueandanti-gastriculcereffectsasshownbyastudyconductedbyAlqasoumi[71].CZsuspensionpre-treatmentdecreasedthebasalgastricacidsecretionvolumeinpylorusligatedratsanditeffectivelyinhibitedgastrichemorrhagiclesionsinducedby80%ethanol,0.2MNaOH,and25%NaCl.Italsoshowedantiulceractivityagainstindomethacin.CZtreat-mentreplenishedtheethanol-induceddecreasedlevelsofgastricwallmucus[71].RaoandLakshmiinduceddiar-rhoeainmiceusingthemagnesiumsulphate-induceddiarrhoeatestandshowedthatCZextractsat100and200mg/kgdosessignificantlyreducedtheextentofthediar-rhoea(71.7%and80.4%)intestanimals[72].Inastudyusingtwoanimalmodelsfortheinvestigationoftheanti-nociceptiveandanti-inflammatoryeffectsofCZandselectedplants,CZinducedadose-dependentan-algesicprotectiveeffectagainstboththermalstimuliandthewrithingsyndrome,furthermore,CZshowedananti-inflammatoryeffectagainstchronicinflammationinducedbycottonpelletgranulomaindicatinganti-proliferativeef-fect[73].TheseeffectshavebeenverifiedbyotherauthorsRanasingheetal.BMCComplementaryandAlternativeMedicine:275Page6of10http://www.biomedcentral.com/1472-6882/13/275 [74].CZisalsoknowntohavewoundhealingpropertiesinrats,inastudyusingthirty-tworatswhereexperimentalexcisionwoundswereinducedandtreatedwithtopicalCZcontainingointments.TheCZextractsservedtoac-celeratethewoundhealingprocessandspecificallyin-creasedepithelialisation[75].InWisterratsCZgivenorallyincreasedthewoundbreakingstrengthsignificantlyinincisionwoundsmodelandindeadspacewoundsthegranulationtissuebreakingstrengthandhydroxyprolinecontentweresignificantlyincreased[76].CZhasalsobeenshowntohavehepato-protectiveef-fectsinastudywhereliverinjurywasinducedinratsby[77].AdministrationofCZextracts(0.01,0.05and0.1g/kg)for28dayssignificantlyreducedtheimpactoftoxicityontheserummarkersofliverdamage(AST,ALTandALP).Inaddition,treatmentwithCZmarkedlyincreasedthelevelsofsuperoxidedismutaseandcatalaseenzymesinrats[77].Water-basedextractfromCZwasapotentinhibitorofVEGFR2kinase(VascularEndothelialGrowthFactorReceptor)activitywhichisinvolvedinangiogenesis[78].Asaresult,CZinhibitedVEGF-inducedendothelialcellproliferation,mi-grationandtubeformationin-vitro,sproutformationfromaorticringex-vivoandtumor-inducedbloodvesselformationin-vivo[78].ToxiceffectsIn-vivostudiesinanimalshavealsohighlightedlackofsig-nificanttoxiceffectsonliverandkidney,withasignifi-cantlyhightherapeuticwindow[51].Domarackýetal.,[79]administeredCZfortwoweekstofemalemiceandevalu-atedtheeffectsontheviabilityofembryosofmice,numberofnucleiandthedistributionofembryosaccordingtonu-cleusnumber.Cinnamonsignificantlydecreasedthenum-berofnucleiandthedistributionofembryosaccordingtonucleusnumberwassignificantlyalteredandthesechangeswereattributedtotheanti-proliferativeeffectsofcinna-maldehyde[79].Howeverthesefindingshavebeencon-tradictedbyotherswhohavedemonstratedthatCZdoesnothavesignificantabortiveorembryotoxiceffectsinani-mals[80].Furthermore,Shahetal,showedthatCZin-ducedasignificantincreaseinreproductiveorganweights,spermmotility,spermcountanddemonstratednosper-matotoxiceffectsinmice[81].Chulasirietal.,demonstratedthatpetroleumetherandchloroformextractsfromCZshowedcytotoxicef-fectsonKB(humanmouthcarcinomacellline)andL1210cells(mouselymphoidleukaemiacellline)[82].TheaverageEDfromthefirstandsecondtestsofthepetroleumetherextractonthesetumourcellswere60and24pg/mlrespectivelyandofthechloroformextractwere58and20pg/mlrespectively.Singh,etal.[83]investi-gatedthecytotoxiceffectsofaqueouscinnamonextractfromthebarkofCZonhumanandmousecelllines.Theaqueouscinnamonextractprovedtobemorecytotoxictocancerouscellsatconcentrationsjustabove0.16mg/mL.Atacriticalconcentrationof1.28mg/mL,CZtreatmentresultedin35-85%growthinhibitionofthemajorityofthecancerouscells.DiscussionTheavailablein-vitroandin-vivoevidencesuggeststhatCZhasanti-microbial,anti-parasitic,anti-oxidantandfreeradicalscavengingproperties.InadditionCZseemstolowerbloodglucose,serumcholesterolandbloodpressure,suggestingbeneficialcardiovasculareffects.ThedifferentpartsoftheCZplantpossessthesamearrayofhydrocarbonsinvaryingproportions.Thischem-icaldiversityislikelytobethereasonforthewide-varietyofmedicinalbenefitsobserved.Itwouldalsobeinterestingtoidentifyprobablemechanismsthatareresponsibleforsuchawidearrayofmedicinalbenefits.ThemechanismofactionbywhichCZreducesbloodglucosehasbeenwellstudiedin-vitroandin-vivo,itseemsthatCZ;a)re-ducesintestinalglucoseabsorptionbyinhibitingenzymes,b)stimulatescellularglucoseuptake,glycogensynthesis,insulinreleaseandpotentiatesinsulinreceptoractivityandc)inhibitsgluconeogenesisbyeffectsonkeyregula-toryenzymes.Themechanismforthelipidloweringeffectsisnotclearlydescribedinliterature.Thehighdietaryfibrecon-tentofCZcouldresultinreducedintestinallipidabsorp-tion,andthehighvitamin/anti-oxidantislikelytoresultinincreasedlipidmetabolism.InsulinplaysakeyroleinlipidmetabolismanditispossiblethatincreasedserumInsulinlevelsfollowingCZadministrationalsocontributesto-wardsreducinglipidlevels.Theexactbloodpressure-loweringmechanismofcinnamonisstillunknownandnewstudiesareneededtoclarifythisissue.Theresultsofstudiesinanimalshaveindicatedthatcinnamonregulatesbloodpressurelevelsthroughperipheralvasodilatation[84].ThisvasodilatationmightbepartiallythroughCachannelsblockingproperties[57].ThephenolicconstituentsofCZarelikelytoberespon-siblefortheanti-oxidantandfreeradicalscavengingactiv-ityobserved.CinnamonextractsareknowntoincreaseTristetraprolinmRNAandproteinlevels,Tristetraprolinshaveanti-inflammatoryeffectsduetodestabilizingofpro-inflammatorymRNA[85].Thiscouldbethereasonfortheanti-inflammatoryactionsobserved.Theanti-microbialactionisconsideredtoarisemainlyfromthepotentialofhydrophobicessentialoilstodisruptthebacterialcellmembraneanditsstructureswhichleadstoionleakage[37].Antibacterialassaysofthecolumnchromatographyfractionsclearlyindicatedthatcinnamaldehydeisthepri-marycompoundresponsibleformajorantibacterialactivity[37].Trans-cinnamaldehydeisalsoknowntoinhibitsbac-terialacetyl-CoAcarboxylase[33].Ranasingheetal.BMCComplementaryandAlternativeMedicine:275Page7of10http://www.biomedcentral.com/1472-6882/13/275 Weacknowledgeseverallimitationtotheextenttowhichconclusionscanbedrawnfromthepresentsys-tematicreview.TheCZspecimenwaseithernotauthen-ticatedorauthenticationdetailswerenotmentionedinmajorityofthestudies,howeverconsideringthatama-jorityofthestudieswereconductedincountrieswhereCZiscultivated,itislikelythatthespeciesusedwerecinnamon.TherewereminimalstudiesevaluatingtheeffectsofCZinhumansandmajorityofthestudiesin-vitroin-vivoinanimals,hencecareneedstobedrawnwhengeneralizingtheconclusionstothehumanpopulation.Inordertohavepublichealthimpli-cationstheseeffectsneedtobereproducibleinhumans.Lackofwell-designedhumantrialshascompromisedourknowledgeoncommonside-effects,druginter-actionsandefficacyinhumans.Furtherrandomizeddouble-blindedplacebo-controlledclinicaltrialsarere-quiredtoestablishtherapeuticsafetyandefficacyofCZasapharmaceuticalagent.ConclusionsTheavailablein-vitroandin-vivoevidencesuggeststhatCZhasanti-microbial,anti-parasitic,anti-oxidantandfreeradicalscavengingproperties.InadditionCZseemstolowerbloodglucose,serumcholesterolandbloodpres-sure,suggestingbeneficialcardiovasculareffects.However,randomizedcontrolledhumantrialswillbenecessarytodeterminewhethertheseeffectshavepublichealthimplications.AdditionalfilesAdditionalfile1:Abriefcomparisonofthetwomainvarietiesofcinnamon(CinnamomumzeylanicumandCinnamomumcassia).Additionalfile2:PRISMA(PreferredReportingItemsforSystematicreviewsandMeta-Analyses)Checklist.CompetinginterestTheauthorsdeclarethattheyhavenocompetinginterests.PR,GASP,PG,GRCandPKmadesubstantialcontributiontoconceptionandstudydesign.PRandSPwereinvolvedindatacollection.PR,SP,GASPandGRCwereinvolvedinrefiningthestudydesign,statisticalanalysisanddraftingthemanuscript.PR,PGandPKcriticallyrevisedthemanuscript.Allauthorsreadandapprovedthefinalmanuscript.AcknowledgementTheauthorswouldliketothankthestaffmembersofDepartmentofPharmacology,FacultyofMedicine,UniversityofColombofortheirsupport.AuthordetailsDepartmentofPharmacology,FacultyofMedicine,UniversityofColombo,Colombo,SriLanka.IndustrialTechnologyInstitute,Colombo,SriLanka.DepartmentofClinicalMedicine,FacultyofMedicine,UniversityofColombo,Colombo,SriLanka.Received:26May2013Accepted:17October2013Published:22October20131.ShenQ,ChenF,LuoJ:ComparisonstudiesonchemicalconstituentsofessentialoilfromramuluscinnamomiandcortexcinnamomibyGC-MS.ZhongYaoCai2.GruenwaldJ,FrederJ,ArmbruesterN:Cinnamonandhealth.CritRevFoodSciNutr3.ParanagamaPA,WimalasenaS,JayatilakeGS,JayawardenaAL,SenanayakeUM,MubarakAM:Acomparisonofessentialoilconstituentsofbark,leafrootandfruitofcinnamon(cinnamomumzeylanicumBlum),growninSriLanka.JNatlSciFoundSri4.ChericoniS,PrietoJM,IacopiniP,CioniP,MorelliI:Invitroactivityoftheessentialoilofcinnamomumzeylanicumandeugenolinperoxynitrite-inducedoxidativeprocesses.JournalAgricFoodChem5.SinghG,MauryaS,DeLampasonaMP,CatalanCA:Acomparisonofchemical,antioxidantandantimicrobialstudiesofcinnamonleafandbarkvolatileoils,oleoresinsandtheirconstituents.FoodChemToxicol6.SimicA,SokovicMD,RisticM,Grujic-JovanovicS,VukojevicJ,MarinPD:Thechemicalcompositionofsomelauraceaeessentialoilsandtheirantifungalactivities.PhytotherRes7.UstaJ,KreydiyyehS,BarnabeP,Bou-MoughlabayY,Nakkash-ChmaisseH:ComparativestudyontheeffectofcinnamonandcloveextractsandtheirmaincomponentsondifferenttypesofATPases.HumExpToxicol8.ArcherA:Determinationofcinnamaldehyde,coumarinandcinnamylalcoholincinnamonandcassiabyhigh-performanceliquidJChromatogr9.BundesinstitutfürRisikobewertung:Highdailyintakesofcinnamon:healthriskcannotberuledout,Bookhighdailyintakesofcinnamon:healthriskcannotberuledout.Germany:BundesinstitutfürRisikobewertung;2006.10.AbrahamK,WöhrlinF,LindtnerO,HeinemeyerG,LampenA:andriskassessmentofcoumarin:focusonhumandata.MolNutrFood11.EuropeanFoodSafetyAssociation:Coumarininflavouringsandotherfoodingredientswithflavouringproperties.EFSAJ12.JayaprakashaGK,RaoLJ:Chemistry,biogenesis,andbiologicalactivitiesofcinnamomumzeylanicum.CritRevFoodSciNutr13.MoherD,LiberatiA,TetzlaffJ,AltmanDG:Preferredreportingitemsforsystematicreviewsandmeta-analyses:thePRISMAstatement.14.AgasthyaAS,JayapalN,NaveenkumarE,GoudNR,VijayanandJ,HemapriyaInvitrostudyofantimicrobialactivityoftheSouthIndianspicesagainstentericpathogens.AsianJMicrobiol,BiotechnolEnvironSci15.BarattaMT,DormanHJD,DeansSG,FigueiredoAC,BarrosoJG,RubertoG:AntimicrobialandantioxidantpropertiesofsomecommercialessentialFlavourFragrJ16.BayoubK,BaibaiT,MountassifD,RetmaneA,SoukriA:activitiesofthecrudeethanolextractsofmedicinalplantsagainstlisteriamonocytogenesandsomeotherpathogenicstrains.AfrJBiotechnol17.BhatiaM,SharmaA:InactivationofcandidiaalbicansinculturemediabyeightspicesnativetoIndiansubcontinent.IntlJPharmSciRevRes18.CarmoES,LimaEDO,DeSouzaEL,DeSousaFB:Effectofcinnamomumzeylanicumblumeessentialoilonthegrowthandmorphogenesisofsomepotentiallypathogenicaspergillusspecies.BrazJofMicrobiol19.DubeyRC,RanaA,ShuklaRK:Antibacterialactivityofessentialoilsofsomemedicinalplantsagainstcertainhumanpathogens.IndianDrugs20.ElumalaiS,KesavanR,RamganeshS,PrakasamV,MurugasenR:Comparativestudyonanti-microbialactivitiesofbarkoilextractfromcinnamomumcassiaandcinnamomumzeylanicum.BiosciBiotechnolRes21.FabioA,CermelliC,FabioG,NicolettiP,QuaglioP:Screeningoftheantibacterialeffectsofavarietyofessentialoilsonmicroorganismsresponsibleforrespiratoryinfections.PhytotherRes22.FerhoutH,BohatierJ,GuillotJ,ChalchatJC:Antifungalactivityofselectedessentialoils,cinnamaldehydeandcarvacrolagainstmalasseziafurfurandcandidaalbicans.JEssentOilResRanasingheetal.BMCComplementaryandAlternativeMedicine:275Page8of10http://www.biomedcentral.com/1472-6882/13/275 23.GonçalvesJLS,LopesRC,OliveiraDB,CostaSS,MirandaMMFS,RomanosMTV,SantosNSO,WiggMD:Invitroanti-rotavirusactivityofsomemedicinalplantsusedinBrazilagainstdiarrhea.JEthnopharmacol24.GuerraFQS,MendesJM,deSousaJP,Morais-BragaMFB,SantosBHC,CoutinhoHDM,LimaEDO:Increasingantibioticactivityagainstamultidrug-resistantacinetobactersppbyessentialoilsofcitruslimonandcinnamomumzeylanicum.NatProdRes25.HosseininejadZ,MoghadamSD,EbrahimiF,AbdollahiM,ZahediMJ,NazariM,HayatbakhshM,AdeliS,SharififarF:InvitroscreeningofselectedIranianmedicinalplantsagainsthelicobacterpylori.IntJGreenPharm285.26.JantanIB,KarimMoharamBA,SanthanamJ,JamalJA:Correlationbetweenchemicalcompositionandantifungalactivityoftheessentialoilsofeightcinnamomumspecies.PharmBiol27.JirovetzL,BuchbauerG,NgassoumMB,Essia-NgangJJ,TatsadjieuLN,AdjoudjiO:Chemicalcompositionandantibacterialactivitiesoftheessentialoilsofplectranthusglandulosusandcinnamomumzeylanicumfromcameroon.SciPharm28.KhanR,IslamB,AkramM,ShakilS,AhmadA,AliSM,SiddiquiM,KhanAU:Antimicrobialactivityoffiveherbalextractsagainstmultidrugresistant(MDR)strainsofbacteriaandfungusofclinicalorigin.29.LimaEO,GompertzOF,GiesbrechtAM,PauloMQ:In-vitroantifungalactivityofessentialoilsobtainedfromofficinalplantsagainst30.MaidmentC,DysonA,HaysomI:Astudyintotheantimicrobialeffectsofcloves(syzgiumaromaticum)andcinnamon(cinnamomumzeylanicum)usingdisc-diffusionassay.NutrFoodSci31.MandalS,DebMandalM,SahaK,PalNK:InvitroantibacterialactivityofthreeIndianspicesagainstmethicillin-resistantstaphylococcusaureus.OmanMedJ32.MasturaM,NorAzahMA,KhozirahS,MawardiR,ManafAA:andantidermatophyticactivityofcinnamomumspeciesessentialoils.33.MeadesGJr,HenkenRL,WaldropGL,RahmanMM,GilmanSD,KamatouGP,ViljoenAM,GibbonsS:ConstituentsofcinnamoninhibitbacterialacetylCoAcarboxylase.PlantaMed2010,76:15701575.34.MishraAK,MishraA,BhargavaA,PandeyAK:Antimicrobialactivityofessentialoilsfromtheleavesofcinnamomumspp.NatlAcadSciLett35.NegiPS,JayaprakashaGK,RaoLJ:Antibacterialactivityofcinnamomumzeylanicumfruitextracts.SciAliments36.NoudehGD,SharififarF,NoodehAD,MoshafiMH,AfzadiMA,BehravanE,ArefM,SakhtianchiR:Antitumorandantibacterialactivityoffourfractionsfromheracleumpersicumdesf.AndcinnamomumzeylanicumJMedPlantsRes37.RanaIS,SinghA,GwalR:Invitrostudyofantibacterialactivityofaromaticandmedicinalplantsessentialoilswithspecialreferencetocinnamonoil.IntJPharmPharmSci38.SenhajiO,FaidM,KalalouI:InactivationofescherichiacoliO157:H7byessentialoilfromcinnamomumzeylanicum.BrazJInfectDis2007,11:234236.39.ShahverdiAR,Monsef-EsfahaniHR,TavasoliF,ZaheriA,MirjaniR:cinnamaldehydefromcinnamomumzeylanicumbarkessentialoilreducestheclindamycinresistanceofclostridiumdifficileinvitro.JFoodSci40.SinghHB,SrivastavaM,SinghAB,SrivastavaAK:Cinnamonbarkoil,apotentfungitoxicantagainstfungicausingrespiratorytractmycoses.Allergyy41.SivakumarA,JayaramanG:Anti-tuberculosisactivityofcommonlyusedmedicinalplantsofsouthIndia.JMedPlantsRes42.TekwuEM,AskunT,KueteV,NkengfackAE,NyasseB,EtoaFX,BengVP:Antibacterialactivityofselectedcamerooniandietaryspicesethno-medicallyusedagainststrainsofmycobacteriumtuberculosis.JEthnopharmacol43.UnluM,ErgeneE,UnluGV,ZeytinogluHS,VuralN:Composition,antimicrobialactivityandinvitrocytotoxicityofessentialoilfromcinnamomumzeylanicumblume(lauraceae).FoodChemToxicol2010,48:32743280.44.AbuElEzzNMT,KhalilFAM,ShaapanRM:Therapeuticeffectofonion(alliumcepa)andcinnamon(cinnamomumzeylanicum)oilsoncryptosporidiosisinexperimentallyinfectedmice.GlobalVet2011,179183.45.RostiL,GastaldiG:Chronicsalmonellosisandcinnamon.46.RostiL,GastaldiG,FrigiolaA:Cinnamonandbacterialentericinfections.IndJPed47.QualeJM,LandmanD,ZamanMM,BurneyS,SatheSS:Invitroactivityofcinnamomumzeylanicumagainstazoleresistantandsensitivecandidaspeciesandapilotstudyofcinnamonfororalcandidiasis.AmJChin48.ZhuM,CarvalhoR,ScherA,WuCD:Short-termgerm-killingeffectofsugar-sweetenedcinnamonchewinggumonsalivaryanaerobesassociatedwithhalitosis.JClinDent49.SamarasekeraR,KalhariKS,WeerasingheIS:Mosquitocidalactivityofleafandbarkessentialoilsofceyloncinnamomumzeylanicum.JEssentOil50.YangYC,LeeHS,LeeSH,ClarkJM,AhnYJ:Ovicidalandadulticidalactivitiesofcinnamomumzeylanicumbarkessentialoilcompoundsandrelatedcompoundsagainstpediculushumanuscapitis(anoplura:IntJParasitol51.RanasingheP,JayawardanaR,GalappaththyP,ConstantineGR,deVasGunawardanaN,KatulandaP:Efficacyandsafetyof(cinnamomumzeylanicum)asapharmaceuticalagentindiabetes:asystematicreviewandmeta-analysis.DiabMed52.BandaraT,UluwadugeI,JanszER:Bioactivityofcinnamonwithspecialemphasisondiabetesmellitus:areview.IntJFoodSciNutr2012,63:380386.53.HassanSA,BarthwalR,NairMS,HaqueSS:Aqueousbarkextractofcinnamomumzeylanicum:apotentialtherapeuticagentforstreptozotocin-inducedtype1diabetesmellitus(T1DM)rats.TropJPharmRes54.JavedI,FaisalI,ZiaUrR,KhanMZ,MuhammadF,AslamB,AhmadM,ShahzadiA:Lipidloweringeffectofcinnamomumzeylanicuminhyperlipidaemicalbinorabbits.PakJPharmSci55.SambaiahK,SrinivasanK:Effectofcumin,cinnamon,ginger,mustardandtamarindininducedhypercholesterolemicrats.56.NyadjeuP,DongmoA,NguelefackTB,KamanyiA:Antihypertensiveandvasorelaxanteffectsofcinnamomumzeylanicumstembarkaqueousextractinrats.IntegrMed:JComplement;2011:8.57.WansiSL,NyadjeuP,NgamgaD,MbuyoEPN,NguelefackTB,KamanyiA:Bloodpressureloweringeffectoftheethanolextractfromthestembarkofcinnamomumzeylanicum(lauraceae)inrats.Pharmacolonline58.MarkeyO,McCleanCM,MedlowP,DavisonGW,TrinickTR,DulyE,ShafatA:Effectofcinnamonongastricemptying,arterialstiffness,postprandiallipemia,glycemia,andappetiteresponsestohigh-fatbreakfast.CardiovascDiabetol59.ChericoniS,PrietoJA,IacopiniP,CioniP,MorelliI:Invitroactivityoftheessentialoilofcinnamomumzeylanicumandeugenolinperoxynitrite-inducedoxidativeprocesses.JAgricFoodChem60.JayaprakashaGK,JaganMohanRaoL,SakariahKK:VolatileconstituentsfromcinnamomumzeylanicumfruitstalksandtheirantioxidantJAgricFoodChem61.JayaprakashaGK,NegiPS,JenaBS,RaoLJM:Antioxidantandantimutagenicactivitiesofcinnamomumzeylanicumfruitextracts.JFoodCompostAnal62.Mancini-FilhoJ,Van-KoiijA,ManciniDA,CozzolinoFF,TorresRP:Antioxidantactivityofcinnamon(cinnamomumzeylanicum,breyne)BollChimicoFarm63.KitazuruER,MoreiraAVB,Mancini-FilhoJ,DelinceeH,VillavicencioALCH:Effectsofirradiationonnaturalantioxidantsofcinnamon(cinnamomumzeylanicumN.).RadiatPhysChem64.MathewS,AbrahamTE:Studiesontheantioxidantactivitiesofcinnamon(cinnamomumverum)barkextracts,throughvariousinvitromodels.FoodChem65.PrakashD,SuriS,UpadhyayG,SinghBN:Totalphenol,antioxidantandfreeradicalscavengingactivitiesofsomemedicinalplants.IntJFoodSci66.RanjbarA,GhasmeinezhadS,ZamaniH,MalekiradAA,BaiatyA,MohammadiradA,AbdollahiM:Antioxidativestresspotentialofcinnamomumzeylanicuminhumans:acomparativecross-sectionalclinicalstudy.67.RanjbarA,GhaseminejhadS,TakaluH,BaiatyA,RahimiF,AbdollahiM:oxidativestresspotentialofcinnamon(cinnamomumzeylanicum)inRanasingheetal.BMCComplementaryandAlternativeMedicine:275Page9of10http://www.biomedcentral.com/1472-6882/13/275 operatingroompersonnel;abefore/aftercrosssectionalclinicaltrial. IntJPharmacol 2007, 3: 482 – 486. 68.PetersonDW,GeorgeRC,ScaramozzinoF,LapointeNE,AndersonRA, GravesDJ,LewJ: Cinnamonextractinhibitstauaggregationassociated withalzheimer ’ sdiseaseinvitro. JAlzheimer ’ sDis 2009, 17: 585 – 597. 69.TakasaoN,Tsuji-NaitoK,IshikuraS,TamuraA,AkagawaM: Cinnamon extractpromotestypeicollagenbiosynthesisviaactivationofIGF-I signalinginhumandermalfibroblasts. JAgricFoodChem 2012, 60: 1193 – 1200. 70.Tsuji-NaitoK: Aldehydiccomponentsofcinnamonbarkextract suppressesRANKL-inducedosteoclastogenesisthroughNFATc1 downregulation. BioorgMedChem 2008, 16: 9176 – 9183. 71.AlqasoumiS: Anti-secretagogueandantiulcereffectsof ‘ cinnamon ’ cinnamomumzeylanicuminrats. JPharmacogPhytother 2012, 4: 53 – 61. 72.RaoHJ,Lakshmi: Anti-diarrhoealactivityoftheaqueousextractofthe barkofcinnamomumzeylanicumlinninmice. JClinDiagnRes 2012, 6: 215 – 219. 73.AttaAH,AlkofahiA: Anti-nociceptiveandanti-inflammatoryeffectsof someJordanianmedicinalplantextracts. JEthnopharmacol 1998, 60: 117 – 124. 74.GanapatyS,BeknalAK: Anti-inflammatoryandanalgesicactivityof cinnamomumzeylanicumleafoil. IndianDrugs 2005, 42: 824 – 825. 75.FarahpourMR,HabibiM: Evaluationofthewoundhealingactivityofan ethanolicextractofceyloncinnamoninmice. VetMed 2012, 57: 53 – 57. 76.KamathJV,RanaAC,ChowdhuryAR: Pro-healingeffectofcinnamomum zeylanicumbark. PhytotherRes 2003, 17: 970 – 972. 77.EidiA,MortazaviP,BazarganM,ZaringhalamJ: Hepatoprotectiveactivity ofcinnamonethanolicextractagainstCCL4-inducedliverinjuryinrats. EXCLIJ 2012, 11: 495 – 507. 78.LuJ,ZhangK,NamS,AndersonRA,JoveR,WenW: Novelangiogenesis inhibitoryactivityincinnamonextractblocksVEGFR2kinaseand downstreamsignaling. Carcinogenesis 2010, 31: 481 – 488. 79.DomarackýM,RehákP,Juhás Š ,KoppelJ: Effectsofselectedplant essentialoilsonthegrowthanddevelopmentofmouse preimplantationembryosinvivo. PhysiolRes 2007, 56: 97 – 104. 80.PellegattiLemonicaI,BorroMacedoAMR: Abortiveand/or embryofetotoxiceffectofcinnamomumzeylanicumleafextractsin pregnantrats. Fitoterapia 1994, 65: 431 – 434. 81.ShahAH,Al-ShareefAH,AgeelAM,QureshiS: Toxicitystudiesinmiceof commonspices,cinnamomumzeylanicumbarkandpiperlongumfruits. PlantFoodsHumNutr 1998, 52: 231 – 239. 82.ChulasiriMU,PichaP,RienkijkanM,PreechanukoolK: Thecytotoxiceffect ofpetroleumetherandchloroformextractsfromceyloncinnamon (cinnamomumzeylanicumnees)barksontumorcellsinvitro. IntJCrude DrugRes 1984, 22: 177 – 180. 83.SinghR,KoppikarSJ,PaulP,GildaS,ParadkarAR,Kaul-GhanekarR: Comparativeanalysisofcytotoxiceffectofaqueouscinnamonextract fromcinnamomumzeylanicumbarkwithcommercialcinnamaldehyde onvariouscelllines. PharmBiol 2009, 47: 1174 – 1179. 84.PreussHG,EchardB,PolanskyMM,AndersonR: Wholecinnamonand aqueousextractsamelioratesucrose-inducedbloodpressureelevations inspontaneouslyhypertensiverats. JAmCollNutr 2006, 25: 144 – 150. 85.CaoH,UrbanJFJr,AndersonRA: Cinnamonpolyphenolextractaffects immuneresponsesbyregulatinganti-andproinflammatoryandglucose transportergeneexpressioninmousemacrophages. JNutr 2008, 138: 833 – 840. doi:10.1186/1472-6882-13-275 Citethisarticleas: Ranasinghe etal. : Medicinalpropertiesof ‘ true ’ cinnamon( Cinnamomumzeylanicum ):asystematicreview. BMC ComplementaryandAlternativeMedicine 2013 13 :275. Submit your next manuscript to BioMed Central and take full advantage of: € Convenient online submission € Thorough peer review € No space constraints or color “gure charges € Immediate publication on acceptance € Inclusion in PubMed, CAS, Scopus and Google Scholar € Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Ranasinghe etal.BMCComplementaryandAlternativeMedicine 2013, 13 :275Page10of10 http://www.biomedcentral.com/1472-6882/13/275