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KAMALA KRISHNASWAMY
Former Director (NIN)
Emeritus Medical Scientist (ICMR)
National Institute o Nutrition! "amai #smania
H$dera%ad & '(( (()! And*ra +rades*
TURMERIC
THE SALT OF THE ORIENT
IS
THE SPICE OF LIFE
KK - 2007
,urmeric - Fenu.ree/ & ,*e Ma.ic In.redients o t*e
Indian Kitc*en
Kamala Krishnaswamy
Former Director (NIN)
National Institute o Nutrition! "amai #smania
H$dera%ad & '(( (()! And*ra +rades*
KK - 2007
Noncommunica%le
conditions o 0*ic*
'(1 are due to C2D
Communica%le
diseases!
maternal and
3erinatal
conditions and
nutritional
deiciencies
in4uries
'5671
89681
:6;1
Source< WH#6 WHR6 9((8
Deat*s! %$ %road cause .rou3
estimates or 9((9
,otal deat*s< ')!(9)!(((
Cardiovascular and
cerebrovascular diseases
Chronic inflammatory
diseases
Obesity
Cataract
Osteoporosis
Neurodegenerative diseases
Aging
C*ronic Diseases o
Clinical -+u%lic Healt*
Si.niicance
KK - 2007
Ancient =uotes on ood and *ealt*
r
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,A :5 J S: ,A ;(( J S:
,urmeric ( ( ; ; ' ' ;( ;(
G(a)+ ( ' ( ' ( ' ( '
( ( ; ; ' ' ;( ;(
( ' ( ' ( ' ( '
D
D
D 3 K (6((;
Similar results 0ere seen 0it* (6;1! (6'1 turmeric 0it* %ot* G(a)+ and 8MC
KK - 2007
H# CH CH C CH
9
C CH CH #H
# #
H
8
C#
#CH
8
H# CH CH C CH
9
C CH CH #H
# #
H
8
C#
H# CH CH C CH
9
C CH CH #H
# #
Curcumin I > Dierulo$l met*ane
Curcumin II > Demet*oA$ curcumin
Curcumin III > Gisdemet*oA$ curcumin
C-+C-,INOIDS
KK - 2007
#ffects of Curcuminoids/ on -rinary ,utagens TA 01
& S : J S :
J
(6('1
&
J
(6(81
&
J
(6(;'1
&
No6 o Re?ertants
J
Control
&
c
c
%
a
c
c
%
a
0 100 200 300
-150 -100 -50 0
150 100 50 0
J Wit* G (a)+ (;m. - Rat) & Wit*out G(a)+L S: < acti?ated MF#sM
2alues %earin. dierent su3erscri3ts are si.niicantl$ dierent < 3K(6(' (Ano?a)
D I > Dierulo$l met*ane! II > Demet*oA$ curcumin! III > Gisdemet*oA$ curcumin
KK - 2007
& S :
J Wit* G (a)+ (;m. - Rat) & Wit*out G(a)+L S: < acti?ated MF#sM
2alues %earin. dierent su3erscri3ts are si.niicantl$ dierent < 3K(6(' (Ano?a)
J S :
No6 o Re?ertants
c
%
%
a
d
c
%
a
#ffects of Curcumin on -rinary ,utagens TA ())
0 200 400 600
J
(6('1
&
J
(6(81
&
J
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&
J
Control
&
-400 -300 -200 -100 0
400 300 200 100 0
KK - 2007
S-,,A+2 O. ANTI,-TA*#NIC ACTI3IT2
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KK - 2007
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2alues are Mean N SE o 7 o%ser?ationsL
Eac* o%ser?ation is a 3ool o 8 animals
a!% < 3K(6(' %et0een .rou3s (Ano?a)
Dierent su3erscri3ts are si.niicant
a
a
a
%
Intestine
$iver
#ffect of Curcumin on *ST Activity
0
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400
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Control (6(;1 C (6(91 C (6(81 C
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Control (6(;1 C (6(91 C (6(81 C
(97671)
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OR! BD+@,! EH
CY+&;A;!
KK - 2007
#ffect of Curcumin on ACA Induced
$ipid ero5idation
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Dierent su3erscri3ts are si.niicant
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Serum AL, le?els
Li?er MDA le?els
Control
Control J ACA+
(6(;'1 Curcumin
(6(81 Curcumin
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AN,I#QIDAN,S EFFEC,S #F
,BRMERIC-CBRCBMIN#IDS DERI2A,I2ES (,HC)
ERY,HR#CY,E
MEMGRANE
@H#S,S
A#R,IC
END#,HELIAL
CELLS
CANCER CELLS
(C#L#N)
LI+ID+ER#QIDE! MDA
MECHANISMS<#QY@EN RADICAL SCA2EN@ERS! LI+ID +ER#QIDE SCA2EN@ERS!
OBENCHIN@ #F SIN@LE, #QY@EN
LI+##QY@ENASE AND CYCL#QY@ENASE! H#&;MRNA! +ER#QIS#ME! ( @+Q! @7+D!
S#D! @LB,A,HI#NE)! NF KG
GRAIN LBN@
KIDNEY
HAEM#@L#GIN LDL
LI2ER
(MICR#S#MES)
MACR#+HA@ES
KK - 2007
Sensiti?e s3ecies
Acti?ates onco.enes
@enetic correlations
DNA ADD-CTS 6 CANC#+
KK - 2007
Eect o ,urmeric and Curcumin on G(a)+&
DNA Adducts in He3atic ,issue
*
D 3K(6(;
86E)
;96;;
:6)9
;'6:;
E;6(5
;68)
(6'8
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@rou3s
rotective #ffect of Curcumin 6 78a9
Induced DNA Damage
(6:88
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G(a)+!
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@rou3s
CB < Curcumin in micromoles
Dierent su3erscri3ts are si.niicantl$ dierent! Ano?a 0it*
Duncan Multi3le ran.e test
a
%
c
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d
a
%
c
d
d
,en
&omen
Strand %rea/s (SS%s) in S6cere?isiae di3loid strain re3aired
KK - 2007
#ffects of T/C on D,7A Induced Tumorigenesis
8"amster Chee%pouch ,odel9
a!% < 3K(6(' + < +aintin. & 8 Wee/sL D < DietL
Duration < ;E Wee/sL DMGA < 7(( H. - 9 0/s
No6 o tumors - animal
a
%
C(+) 71
C(D)(6(81
C(+) 6( 71
,(D) ;1
,(+) ;(1
C(+) (671
,(+) ;(1
J Control
( 9 E
-40 -20 0
,umor %urden in mm
8
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KK - 2007
( 7(
2II
2I
2
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III
II
I
G(a)+ G(a)+ J (6(91 Curcumin
;1 ,urmeric (6(91 Curcumin
G(a)+ J;1 ,urmeric Stoc/ Diet
@rou3s
Strain : swiss mice (ale)
!uration : 60 w"s
!ose : 1.5mg # 4 $ 10 w"s
%oute : &a'age
(arget organ : )orestomac*
+nitiation : 0-10 w"s
,ost initiation : 11-60 w"s
#5perimental Design : 78a9 Induced .ore Stomach
Carcinogenesis
Wee/s ;(
;6 Normal mucosa
96 H$3er/eratosis
86 Acant*osis ocal
E6 Acant*osis diuse
'6 +a3illar$ ocal
76 H$3er3lasia diuse
)6 +a3illomas R adenomas
56 D$s3lasia ocal
:6 Carcinoma in situ
;(6In?asi?e s=uamous cell
carcinoma (ISCC)
NE#+LAS,IC INDEQ
(CELLBLAR E2EN,S IN
CARCIN#@ENESIS)
KK - 2007
Eect o , - C on G(a)+ Induced Forestomac* Carcino.enesis
+rolieration IndeA ;&;(
G(a)+
,
C
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-alues are ean . S/
( ) : 0o. o1 2nimals
(3 (urmeric 14
C3 Curcumin 0.024
+ 3 +nitiation (10w"s)
,+3 ,ost +nitiation (50w"s)
0on ,arametric (est
5 6 0.001 or 0.01
!ose 7(a), 1.5mg # 4 $ 10 w"s
78 ga'age
-alues are ean . S/
( ) : 0o. o1 2nimals
,roli1eration in9e#
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KK - 2007
878a9 /TA' D,7A/TA' Nitrosamine' AO,' D,"' +adiation/viral ;
induced tumors9 Delay in onset' number/volume
C"#,O+#3#NTI3# /T-,O+ICIDA$ #..#CTS
O. T-+,#+IC /C-+C-,IN
,urmeric and its eAtracts curcumin
Curcumin ree 0ater eAtract
(Diet -local a33lication)
S%in
rostate
.ore stomach
$iver
$ung 7reast
Colon
Oral cavity
Several
cells lines
KK - 2007
Turmeric Doses in Diet and
+elevance to "umans
1 o ,urmeric in Diet
Diet inta/e ;' .-da$
Human Doses D
m.-/.
.-'(/.
.-)(/.
(6;
;' m.
56:
(6E'
(679
(6'
E' m.
EE67
968
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5:69
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D +*armacolo.ical %asis
Freireic* et al6! ;:776
KK - 2007
(
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-rinary ,utagens 6 In Smo%ers
a
%
%
%
%
a
Non Smo/ers
2alues %earin. dierent su3erscri3ts are si.niicantl$ dierent
(3K(6((;) 0it*in eac* cate.or$
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TA ())
a
%
%
%
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KK - 2007
E+IDEMI#L#@Y
+re?alence o +reneo3lastic lesions & 9(( - ;(((
Incidence o +reneo3lastic lesions & ;(7 - ;(((
Mali.nant transormation & (67 - ;((( - $r
Incidence o mali.nanc$ & ;E - ;((!(((
Me*ta et al! ;:5(
KK - 2007
'(1 s*o0ed remission
0it*in : mont*s ?s
;(1 natural remissions
KK - 2007
Eect # ,urmeric (;.-d) #n Micronuclei
*
D +K(6((;!
( ) No o Su%4ects
Eect o ,urmeric (;.-d) on DNA adducts
3K(6((;!
( ) No o su%4ects
5.=
<.6
0
5
10
15
7( (25) 2( (25)
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*
KK - 2007
In Vivo Nitrosation
8$6roline Test9
;6 Gaseline
96 '((m. +roline
86 '((m. +roline J '. ,urmeric
E6 '((m. +roline J 9. ,urmeric
'6 '((m. +roline J ;. ,urmeric
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In&?itro ED6'( & ;6;' to 86'E .
1 2 3 4 5
KK - 2007
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,urmeric Bn%oiled ,urmeric Goiled
ENO#
,urmeric
J J J
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IN"I7ITION O. SOS +#SONS# IN #< CO$I 72 T-+,#+IC
Inihibition of SOS +esponse in #<Coli by Curcumin
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Curcumin (n.)
ENO# (;(n.)
J J J
SC
J
SC
Curcumin ;(n. Curcumin 8(n. Curcumin '(n.
KK - 2007
Cell 3rolieration
mito.enesis c$clin D;
Si.nal
transduction
+rotein/inases
(C&"un n&terminal
+KC MA+KS ,ranscri3tion actors
NF&/G! A+&;! E.r! IG
/inase
#nco.ene eA3ression
C&"un! Cm$c! Gcl&9!
Gcl&Al
+'8 -+ro.rammed
cell deat*
2ascularit$
s3read
DetoAiication
Inlammation
DNA
dama.e
#Aidant
enI$mes
E3idermal
.ro0t*actor
,elomerase
AN,I CANCER AC,I2I,Y #F
CBRCBMIN M#LECBLAR
MECHANISMS
KK - 2007
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C*oloretic
KK - 2007
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curcumin ((6((91) & E 0ee/s
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KK - 2007
CBRCBMIN #N #,HER
DISEASES
Anti
Ne3*rotoAic
Anti&
*e3atotoAic
AlI*eimers
3la=ues
Anti&AIDS (re3lication
enI$mes)
Anti&
cataracto.enesis
S/in 3ro%lems
(3soriasis)
M$ocardial
in4ur$
Lun.
diseases
Anti&
dia%etes
Radiation
in4ur$
Gone
resor3tion
AN,I#QIDAN, R AN,I&INFLAMMA,#RY EFFEC,S
KK - 2007
To5icology #valuation Studies on
Turmeric / Curcumin
Animal ,oAicit$ Dosa.e Sc*edule Eect
model test
Rat Acute 5(&;5(( m. - /. A)D Not let*al
Mouse Curcumin
Rat C*ronic ;5(( m.! 5(( m.-/. No E?idence o
%od$ 0t6 A :(( a%normalities
Curcumin
Mice ,erato& 5((&;7(( Not terato.enic
Ra%%it .enic 8((&7(( m.-/.
%od$ 0t6 Curcumin
Mice @enetic Same as a%o?e No si.niicant
Ra%%it c*an.e in c*romo&
Mon/e$ somal a%errations
KK - 2007
C$INICA$ T+IA$S IN "-,ANS
ANTI6IN.$A,,ATO+2 ACTI3IT2
(< +heumatoid arthritis
=< ost operative inflammation
>< Idiopathic orbital tumors
?< Chronic anterior -veitis
OT"#+ #..#CTS
(< eptic ulcer 8"ealing9
=< soriasis 8ph@/histology9
>< "yperlipidemia
?< Normal 3olunteers
8chole%inetic9
ANTI CANC#+
(< recancer and Cancer
=< Oral pre cancerous lesions
>< Colo rectal cancers
?< ,utagens in smo%ers
A< DNA damage in lymphocytes
Double blind cross over' Open trials' $aboratory studies'
Oral curcumin and turmeric' Ointment of turmeric' T#' TO+
Dose: Turmeric (6(<A g/d B Duration : Ad60 months
Curcumin A)) mg ; (=g/day ,ost studies :?6C months
Curcumin +ro3osed as c*emo3re?entor
Multi3le m$eloma @I ,ract cancer
+ancreatic cancer Melanoma
Colon Cancer AlI*eimerMs Disease
+rostate Cancer M$elod$s3lastic s$ndrome
Cer?ical Cancer
KK - 2007
$#IOT+OIC #..#CTS O. C-+C-,IN
AN,ICANCER
AN,I&
A,HER#SCLER#,IC
AN,I&
INFLAMMA,#RY
CANCER
CARDI# 2ASCBLAR
DISEASES
INFLAMMA,#RY
DIS#RDERS
DE@ENERA,I2E
DIS#RDERS
AN,I&INFEC,I2E AN,I&DE@ENERA,I2E
-The salt of the Orient Is the Spice of life
Turmeric
KK - 2007
Nutrient Composition of .enugree%
8Trigonella foenum graecum9
,acronutrients 8g/())g9
Com3onent Lea?es Seeds
Moisture 576; 96E
+rotein E6E 9'6E
Fat (6: )6:
N8 att$ acids (69 96(
,otal dietar$ i%er E6) E5
Insolu%le dietar$ i%er 869 95
Solu%le dietar$ i%er ;6' 9(
As* ;6' 86:
Car%o*$drate 7 867
Source < @o3alan et al 9((( (Nutriti?e ?alue o Indian oods)
Srid*ar R La/s*minara$ana! ;::8
+BS Rao R S*arma ! ;:5)6
@*aoorunnisa R +an.re/ar "! ;::8
Wealt* o India (;:)7)! 2ol Q! 3u%lis*ed %$ CSIR
KK - 2007
,ime in *ours
G
l
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o
d
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l
u
c
o
s
e
(
m
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-
d
l
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Eect o enu.ree/ seeds on oral @,, in NIDDM
Duration < ;( da$s
;(( . deatted enu.ree/ seed 3o0der
*
Source < Sarma! RD and Ra.*uram ,C & Nutr6 Res6 ;::(L ;(< )8;&:
KK - 2007
#ffect of .enugree% Seeds on Serum Insulin
$evels
0
1 0
20
30
4 0
50
60
0 6 0 5 1 6 1 5 2
Geore Ater
ABC < Area under Cur?e
Le?el o si.niicance D3K(6('
Source< S*arma RD and Ra.*uram ,C! ;::(
D
D
D
D
0
1 0 0 0
20 0 0
30 0 0
4 0 0 0
D
ABC
m
B
-
l
m
B
-
m
l
-
l
<
m
i
n
Hours
KK - 2007
#ffect of .enugree% seeds on =?h -rinary
sugar and serum lipids 8,ean D S#9
0
4
8
1 2
1 6
20
24
1 1 0
1 30
1 50
1 70
1 90
21 0
230
2 20
2 30
2 4 0
2 50
2 60
2 70
2 80
2 90
30 0
31 0
320
330
34 0
350
360
Brinar$ su.ar
(.-9E*)
Serum C*olesterol
(m.-dl)
Serum ,ri.l$cerides
(m.-dl)
Geore Ater ;( da$s Ater 9( da$s
*
*
*
*
*
Source< S*arma RD and Ra.*uram ,C! ;::(
D 3K(6('
KK - 2007
Eect o Fenu.ree/ on I2 @,, in ;( ,$3e 9 Dia%etes
+arameter Control diet Fenu.ree/ diet
(9'. - da$)
Glood .lucose
ABC (m.-ml6 min) ;'96E N ;(65 ;8565 N 769 D
Hal lie (*ours) ;6)' N (6;8 ;68E N (6() DD
Clearance (ml-min) 9;767 N ;:69 99:6; N ;56;DDD
2olume o distri%ution 8;6: N 967 976' N 96; DD
(L)
RGC insulin rece3tors ;E6' N '6: ;76; N )69 DD
(n.-ml)
Statistical anal$ses %$ 3aired TtM test6
D + K(6('L DD + K(6(;L DDD + K(6(;L
Source < Ra.*uram et al! ;::E
KK - 2007
.enugree% and Cataract
8#5perimental Studies9
0
1 0
20
30
4 0
50
60
70
80
90
1 0 0
S,F (Dia%etic) & J J J J
Fenu.ree/ (1) & & ' ;( 9(
Water content @lucose content (li?er - 3lasma)
Aldose reductase Sor%ital de*$dro.enase
@SH #Aidati?e stress #smotic stress
G*anu3ra/as* Redd$ et al6! 9((8
KK - 2007
#..#CTS O. ONIONS AND *A+$IC