Boswellia carterii Extract Inhibits TH1 Cytokines and Promotes TH2 Cytokines In Vitro

  • 格式:pdf
  • 大小:265.93 KB
  • 文档页数:6

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.