Boswellia carterii Extract Inhibits TH1 Cytokines and Promotes TH2 Cytokines In Vitro
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CLINICALANDDIAGNOSTICLABORATORYIMMUNOLOGY,May2005,p.575–580Vol.12,No.51071-412X/05/$08.00ϩ0doi:10.1128/CDLI.12.5.575–580.2005Copyright©2005,AmericanSocietyforMicrobiology.AllRightsReserved.
BoswelliacarteriiExtractInhibitsTH1CytokinesandPromotesTH2
CytokinesInVitro
MarcR.Chevrier,1†AbigailE.Ryan,1DavidY.-W.Lee,2MaZhongze,2ZhangWu-Yan,2
andCharlesS.Via1*
ResearchService,BaltimoreVAMHCSandDivisionofRheumatologyandClinicalImmunology,UniversityofMarylandSchoolofMedicine,Baltimore,Maryland21201,1andMcLeanHospital,HarvardMedicalSchool,Belmont,Massachusetts2
Received18November2004/Returnedformodification14January2005/Accepted23February2005
TraditionalherbalformulasusedtotreatinflammatoryarthritisinChinaandIndiaincludeBoswelliacarteriiorBoswelliaserrata.Theybothcontainboswellicacids(BAs)whichhavebeenshowntoexhibitanti-inflammatoryandantiarthriticproperties.ThisstudyteststhehypothesisthatmixturesofBAsderivedfromB.carteriihaveimmunomodulatoryproperties.B.carteriiplantresinobtainedfromChinawaspreparedasanethanolextract,andthepresenceofsevenBAswasconfirmedbycolumnchromatography,high-performanceliquidchromatography,andUVlaserdesorption/ionizationtandemmassspectroscopy.TheextractwasthentestedforitsabilitytoalterinvitroproductionofTH1cytokines(interleukin-2[IL-2]andgammainterferon)andTH2cytokines(IL-4andIL-10)bymurinesplenocytes.Deliveryoftheresinextractusingethanolasasolventresultedinsignificantcellulartoxicitynotseenwiththeadditionofethanolalone.Bycontrast,deliveryoftheresinextractusingasesameoilsolventresultedinadose-dependentinhibitionofTH1cytokinescoupledwithadose-dependentpotentiationofTH2cytokines.TheseresultsindicatethatapurifiedmixtureofBAsfromB.carteriiplantresinexhibitscarrier-dependentimmunomodulatorypropertiesinvitro.
Complementaryandalternativetreatmentsofarthritishave
gainedpopularitybecausetheyarepurportedtoshowclinical
efficacywithminimalsideeffectscomparedtomainstream
treatments.Frankincense,orolibanum,isobtainedfromthe
genusBoswellia,familyBurseraceae,tree.Itsextractedresin,
salaiguggal,isproducedpredominantlybyfourspecies,includ-
ingBoswelliaserratainIndia,BoswelliacarteriiinEastAfrica
andChina,BoswelliafrereanainSomalia,andBoswelliasacra
inArabia(4,7,21).Thetermguggalscollectivelyreferstogum
resins.TheBoswelliagumoleoresiniscomprisedofessential
oils,gum,andterpenoids.TheBoswelliaresin’schemicalstruc-
tureissimilartothatofotherpentacyclictriterpenes,which
closelyresemblesthatofanti-inflammatorysteroids.Salaigug-
galhasbeenshowntoexhibitstrongimmunostimulantactivity
(17),andintheAyurvedicIndiantradition,inflammatorypoly-
arthritisandotherformsofrheumatismhavebeensuccessfully
treatedwithherbalmixturescontainingBoswelliaresinsor
extracts(16).
TheactiveconstituentsarecontainedintheextractedBo-
swelliaterpenoidportionandarecomposedofboswellicacids
(BAs)(20).Theherbalformulasusedfortreatmentvary,with
BAsconstitutingfrom37.5%to65%ofthetotalformulation
(1).TheplantresinfromB.carteriiisafrequentconstituentof
traditionalChineseherbaltherapy,whereasBAsfromB.ser-
rataarekeyingredientsinAyurvedictreatmentsforsimilardiseasestates(1).BothspeciescontainBAsreportedtohave
anti-inflammatoryproperties(2).
Humanrheumatoidarthritishasastrongimmune-mediated
componentandismarkedbyincreasedactivatedlevelsofTH1
cellsandtheircytokines,interleukin-2(IL-2)andgammain-
terferon(IFN-␥),withfewerimmunomodulatoryTH2cells
andtheircytokines,IL-4andIL-10(11,18).Itispossible,then,
thatthebeneficialeffectofboswellinsininflammatoryarthritis
mayderiveinpartfromimmunomodulatoryactivityinaddi-
tiontoanti-inflammatoryproperties.
Inthisstudy,weaddresstheinvitroimmunomodulatory
capacityofBAsderivedfromB.carterii.Moreover,weapplied
bothquantitativechromatographictechniquesandlaserde-
sorption/ionizationtandemmassspectroscopytoensure
propercharacterizationandquantificationofBAspresentin
thepreparationand,thereby,properstandardization.Ourre-
sultssupportthehypothesisthataportionofthetherapeutic
*Correspondingauthor.Presentaddress:DepartmentofPathology,UniformedServicesUniversityoftheHealthSciences,4301JonesBridgeRoad,Rm.B3100,Bethesda,MD20814-4799.Phone:(301)295-3801.Fax:(301)295-1640.E-mail:cvia@usuhs.mil.†Presentaddress:HumanGenomeSciencesInc.,14200ShadyGroveRd.,Rockville,MD20850.TABLE1.Observedversusexpectedmassesofboswellicacidspresentintheinitialacidextract(BCE)asdeterminedbyMS/MSanalysis
BAspeciesaFormulaMHϩpredictedavgmass(AMU)MNϩpredictedmass(AMU)MNaϩobservedmass(AMU)
␣/-BAC30H48O3456.7478.4478.6acetyl-␣/-BAC32H50O4498.7520.4520.811-keto--BAC30H46O4470.7492.3492.9acetyl-1-keto--BAC32H48O5512.7534.4534.6acetyl-11-dien--BAC32H49O4497.7519.4519.5
aExperimentaldetailsareasdescribedinthelegendofFigure3andinMaterialsandMethods.