The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease

501 Pages·2007·5.09 MB·English

by  Bharat B. Aggarwal

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The Molecular Targets
and Therapeutic Uses
of Curcumin in Health
and Disease
i
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ADVANCESINEXPERIMENTALMEDICINEANDBIOLOGY
EditorialBoard:
NATHANBACK,StateUniversityofNewYorkatBuffalo
IRUNR.COHEN,TheWeizmannInstituteofScience
DAVIDKRITCHEVSKY,WistarInstitute
ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch
RODOLFOPAOLETTI,UniversityofMilan
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THEMOLECULARTARGETSANDTHERAPEUTICUSESOFCURCUMIN
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EditedbyBharatB.Aggarwal,Young-JoonSurhandShishirShishodia
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ii
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Bharat B. Aggarwal
Young-Joon Surh
Shishir Shishodia
Editors
The Molecular Targets
and Therapeutic Uses
of Curcumin in Health
and Disease
With 77 Illustrations
iii
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Editors
BharatB.Aggarwal,Ph.D.
RansomHorne,Jr.,ProfessorofCancerResearch
ProfessorofCancerMedicine(Biochemistry)
andChief,CytokineResearchSection
DepartmentofExperimentalTherapeutics
TheUniversityofTexasM.D.AndersonCancerCenter
1515HolcombeBoulevard,BOX143,Houston,TX77030,USA
[email protected]
Young-JoonSurh,Ph.D.
ChiefandProfessor
NationalResearchLaboratoryofMolecularCarcinogenesis
andChemoprevention
CollegeofPharmacy
SeoulNationalUniversity
Shillim-dong,Kwanak-gu,Seoul151-742,SouthKorea
[email protected]
ShishirShishodia,Ph.D.
AssistantProfessor
DepartmentofBiology
TexasSouthernUniversity
3100CleburneStreet,Houston,TX77004,USA
[email protected]
LibraryofCongressControlNumber:2006938892
ISBN-13:978-0-387-46400-8 e-ISBN-13:978-0-387-46401-5
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Dedicatedtoourgurusandparentswhoseguidancecontinuestoinspireus!
Sarvebhavantusukhinahsarvesantuniramayah
Sarvebhadranipasyantumakascidduhkhabhagbhavet
“Mayallbehappy;mayallbehealthy;
mayallenjoyprosperity;maynonesuffer.”
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PREFACE
Thesubjectofthismonograph,curcumin,whichgivestheyellowcolortoturmeric,
bestknownasHaridrainSanskrit(meansdeartoHariorLordKrishna).Turmeric
is known by several synonyms related to its appearance or use, including Pita
(yellow,leadingtothenamePeethamberdhariforLordKrishnabasedonwearing
onlyyellowclothes),Gauri(brilliant),Kanchani(lookslikegold),Nisha(beautiful
as a full moon night), Krimighni (antibacterial and antihelmenthic), Mahaghni
(antidiabetic), and Yoshit priya (gynecological disorders). In Hindi, turmeric is
known as Haldi, in Japanese as Ukon or Gajyutsu, and in Korean as Ulgeum or
Gangwhang.
TurmericismentionedinthewritingsoftheItalianexplorerMarcoPolo,who
was introduced to it during his voyage to China and India around 1290 ad. Al-
thoughhegetscreditforbringingFarEastspicestoEurope,turmericwasactually
introducedinEuropeinthe13thcenturyadbyArabtraders.ThePortugueseex-
plorerVascodeGamavisitedtheIndiansubcontinentduringthe15thcenturyand
broughtturmericandotherspicesoftheOrienttotheWest.Itwasonlyduringthe
ruleoftheBritishinIndiathatturmericwascombinedwithvariousotherspices
andrenamed“currypowder,”asitiscalledintheWest.
Turmeric became of special importance to man with the discovery that when
added to various food preparations, its dried and powdered rhizome preserved
theirfreshnessandnutritivevalueandimprovedthepalatabilityandpresentation
of food. The brilliant yellow color of turmeric, which persists even at very high
dilutions,founditswaytocommercialuseasacoloringagentforvariousitems,
includingcotton,silk,paper,wood,foodstuffs,andcosmetics.InAyurveda(science
of long life), turmeric has been used internally as a stomachic, tonic, and blood
purifier and topically in the prevention and treatment of skin diseases. Turmeric
concoctionshavebeentraditionallyusedforthetreatmentofflatulence,dyspepsia,
liverdisorder,jaundice,urinarytractdiseases,cold,chronicotorrhea,parasiticskin
infection,bruises,sprain,wound,infectedwound,andinflammation.
Wearecurrentlylivinginanerawhen80%oftheworld’spopulationcannotaf-
fordmodernmedicine.Evenforthose20%whocan,muchofmodernmedicineis
ineffectiveandhasnumeroussideeffects.Itisagoodtimetorevivethemedicinal
useoftheancientmedicinecurcumin.Inthisvolumewebringtogetherthecon-
tributionofmodernsciencetooneofthemostancientspicesknowntomankind.
Curcumin’sbeneficialroleinhealthanddiseaseanditsmoleculartargetsarethe
focusofthismonograph.Thisvolumeisdirectedatcliniciansandscientistswork-
ingintheareasofexperimentalandmoleculartherapeutics,molecularmedicine,
translational cancer research, Ayurveda, herbal medicine, naturopathy, and bio-
medicalsciencesingeneraland,mostimportantly,totheendusersofcurcumin.
Wehopethatthisbookwill“addspicetoeverybody’slife.”
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viii PREFACE
Wewouldliketothankallofthecontributorsfortheirvaluablecontributionsto
thiswork.Wewouldalsoliketothankthosewhohavecontributedsignificantly
tocurcuminresearchbutcouldnot,becauseoflimitationsonspace,beinvitedto
contribute.
BharatB.Aggarwal,Ph.D.
Young-JoonSurh,Ph.D.
ShishirShishodia,Ph.D.
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FOREWORD
ItisindeedamatterofprideandprivilegetowritetheForeword;tothisscholarly
contribution on curcumin—the major constituent of turmeric. The volume has
beensuccessfulinseamlesslyconnectingthetraditionalknowledgeavailableon
turmeric to the findings of systematic modern research on turmeric and, based
onthiseffort,buildingthepossibilitiesofdevelopingnoveldrugstotreatdiverse
diseases.Turmeric(Curcumalonga)—awidelycultivatedtropicalplant—hasbeen
used since ancient times as a spice, as a beauty care agent, and as a traditional
medicine.
Therhizomeofturmericishighlyaromaticandantiseptic.Themedicinalprop-
erties of turmeric have been expounded in Ayurvedic and traditional Chinese
medicine (TCM) texts. Turmeric is traditionally known as a stomachic, blood
purifierandisusefulforthecommoncold,leprosy,intermittentfevers,afflictions
oftheliver,indolentulcer,pyogenic(formingpus)afflictions,wound-healing,and
inflammation.
In recent years, the medicinal properties of turmeric have increasingly been
recognized. It is being researched systematically even in the Western world. I
rememberfightingthe“turmericbattle”onthewrongpatentonthewound-healing
propertiesofturmericthatwasgivenbytheUSPatentOfficealmostadecadeago.
AspertheUSNationalLibraryofMedicine,256researchpaperswerepublished
lastyearoncurcumin.Theresearchershavefoundincurcuminanear-perfectstart-
ingmaterialfordrugdiscovery.Thus,avarietyofcurcuminanalogueshavebeen
preparedandevaluatedbiologically.Curcuminexhibitsawiderangeofactivities
[e.g.,antibacterial,anti-inflammatory,hypolipidemic,hepatoprotective,lipoxyge-
nase (LOX), cyclooxygenase (COX), protease inhibitory effects, in addition to
being effective as an active oxygen scavenger and lipid peroxidase (a class of
oxidoreductase enzymes) inhibitor]. Curcumin and the curcuminoids also lower
cholesterol, reduce platelet aggregation, inhibit the proliferation of cancer cells,
and improve digestion by increasing the flow of bile from the gallbladder. The
desirablepreventiveorputativetherapeuticpropertiesofcurcuminhavebeencon-
sideredtobeassociatedwithitsantioxidantandanti-inflammatoryproperties.
Curcuminhasbeenfoundtomodulatetheactivityofseveralkeytranscription
factorsand,inturn,thecellularexpressionprofiles.Theeffectofcurcuminhasbeen
examinedonmostofthetargetsdiscoveredwithinthelastthreedecades.Curcumin
modulatesseveraldifferenttranscriptionfactors,cytokines,growthfactors,kinases
andotherenzymes.Theresearchresultshavebeenelaboratelycoveredinthisbook
andexplanationsprovidedwouldaddtoknowledgepool.
The National Institutes of Health has four clinical trials in progress on cur-
cumin treatment, namely for pancreatic cancer, multiple myeloma, Alzheimer’s
disease, and colorectal cancer. Curcumin has been found to possess potential
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x FOREWORD
chemopreventiveactivities.Itshowscytotoxicpotentialagainsttumorcellsboth
in vitro and in vivo. Thus, curcumin fits well in the effort of chemoprevention
byediblephytochemicals,whichisnowconsideredtobeaninexpensive,readily
applicable,andaccessibleapproachtocancermanagement.Theoptimizationof
interventiontrialsofdiet-derivedputativechemopreventiveagentsiscurrentlyun-
derdevelopmentinnormalpopulationsaswellasinhigh-riskgroups.Curcuminis
alsoagoodimmunomodulator.Thesebiologicalactivitieswarrantfurtherstudies
ofcurcumininthetreatmentandpreventionofhumanneoplasm.
Curcuminhasenormouspotentialasanantiangiogenicdrug.Ithasbeenelabo-
ratelyexplainedinthechapterdiscussingthis.Thepropertyhasbeenattributedto
curcumin’sabilitytodownregulatecertaintranscriptionfactorsandproangiogenic
factors.Curcuminalsohasthenecessarycharacteristicsofaneuroprotectivedrug.
The activity has been proven in a variety of disease models. Thus, it has great
potentialforthepreventionofmultipleneurologicalconditionsforwhichcurrent
therapeuticsarelessthanoptimal.Thechapterentitled“NeuroprotectiveEffects
of Curcumin” embodies the research carried out on the subject and the existing
necessityforfurtherefforts.Thecurcumin-mediatedregulationofCOXandLOX
enzymesforobtainingtheirbeneficialeffectsinpreventingdiverseinflammatory
diseases has been dwelt upon in another chapter. Interestingly, curcumin has an
edgeoverconventionalnonsteroidalanti-inflammatorydrugsandselectiveCOX-2
inhibitors.Thismightpavethewayforpath-breakingresearchinthedomain.
This volume in fact covers the length and breadth of research undertaken on
curcuminandresearchresultsthusfarobtained.Thediversityrangesfrommolec-
ulartargets,cellgrowthregulation,antioxidantandanti-inflammatoryproperties,
chemosensitivity, radio protection, and radio sensitivity to immunomodulation,
anticancer effects, cardioprotective effects, nephroprotective to hepatoprotective
effects,protectionfromacuteandchroniclungdiseasestopharmacokineticsand
pharmacodynamics and clinical studies undertaken with curcumin. The canvas
thuscoveredisindeedbrilliant.
As research advances, it poses newer challenges as well. Several questions in
thelightofthenewdrugdevelopmenteffortthusremaintobeansweredinorder
toputcurcumininahigherorbit.Thesepertaintothesolubilityandstabilityof
curcumin,itsoptimumdose,pharmacokinetics,mechanismofactionofcurcumin
foragivendisease,bioavailabilityprofile,andintricaciesofpreventionandcure
ofanidentifieddisease.Furtherresearchisthusnecessaryontheseaspects.There
is also a need to find out whether other components of turmeric than curcumin
havebeneficialeffects,eitheraloneorincombinationwithcurcumin.
Iamhappytoseethatthecontributionsinthisbookhaveprovenbeyonddoubt
thatcurcumin—aningredientofthetraditionalIndianspiceturmeric—hasenor-
mous potential against a variety of malignant and nonmalignant diseases. I am
confident that the state-of-the-art on curcumin research so nicely compiled and
analyzedthroughoutthisvolumewouldprovideaninsightandlearningnotonlyto
professionalsinthefieldbutalsotobuddingresearchers.Ihopethattheywouldbe
inspiredtoanswertheunansweredquestionsoncurcuminbasedonnewresearch