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Curcumin:Getting Back
to Our Roots!
OH
O O
OCH3CH3O
HO
Diferuloylmethane
Structure of CurcuminFrom turmeric (curry powder)
Milobedzka J., von Kostnecki St, and Lampe V: Zur Kenntnis des curcumins. Ber Deutsch Chem Ges, 1910, 43, 2163-2170
Curcumin data base
1186 curcumin analogs,
195 molecular targets,
10737 peer reviewed publications,
489 patents and
176 varieties of C. longa
Database (Oxford). 2015 Jul 27;2015:bav070.
Curcumin Resource Database.
Kumar A, Chetia H, Sharma S, Kabiraj D, Talukdar NC, Bora U
Pharmacological basis for the role of
curcumin in chronic diseases: an age-old
spice with modern targets.
Aggarwal BB, Sung B.
Trends Pharmacological Sciences.
2009 Feb;30(2):85-94.
Pharmacological basis for the role
of curcumin in chronic diseases:
an age-old spice with modern
targets.
Aggarwal BB, Sung B.
Trends Pharmacological Sciences.
2009 Feb;30(2):85-94.
Discovery of curcumin, a component of golden spice, and its miraculous biological activities.
Gupta SC, Patchva S, Koh W, Aggarwal BB.
Clinical and Experimental Pharmacology and Physiology. 2012 Mar;39(3):283-99.
Curcumin From turmeric
Antibacterial action of
curcumin and related
compounds.
SCHRAUFSTATTER E, BERNT H.
Nature. 1949 Sep 10;164(4167):456.
Curcumin is as potent as hydrocortisone
and phenylbutazone
Anti-inflammatory and irritant activities of curcumin analogues in rats. Mukhopadhyay A et al Agents Actions. 1982
Activation of transcription factor
Nuclear Factor-kappa B is
suppressed by curcumin
Singh S, and Aggarwal BB.
J Biol Chem. 1995 Oct 20;270 (42):24995-5000.
Curcumin Downregulates Expression of Cell
Proliferation, Antiapoptotic and Metastatic Gene
Products Through Suppression of IkBa Kinase and AKT Activation
Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB.
Molecular Pharmacology
[2006 Jan;69(1):195-206]
Preclinical data with curcumin
against various cancers
Gynecologic cancers(Cervix, Ovary, Uterus)Thoracic/ H&N Cancers
(Lung, Oral, Thymus)
Breast cancer
Curcumin
Melanoma
Bone cancer
Brain tumors
Gastrointestinal cancers(Esophagus, Intestine, Liver
Stomach,Pancreas,Colorectal)
Genitourinary cancers(Bladder, Kidney, Prostate)
Hematological cancers(Leukemia, Lymphoma
Multiple myeloma)
Curcumin and cancer: an "old-age" disease with an "age-old" solution.Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Cancer Lett. 2008;267:133-64.
Regulation of production and action of TNF by curcumin
1Ahmed T, 2009
2Zsila F, 2004
3Reddy S, 1994
4Matsunaga T, 2009
5Lin R, 2008
6 Muthenna P, 2009
7Sneharani AH, 2009
8Bilmen JG, 2001
9Yanagisawa D, 2010
10Luthra PM, 2009
11Bourassa P, 2010
12ShimJS, 2004
13Innocenti A, 2010
14Sahu A, 2008
15Shim JS, 2003
16Gafner S, 2004
17Baum L, 2004
18Takeuchi T, 2006
19Leung MM, 2009
20Rai D, 2008
21Hayeshi R, 2007
22Bustanji Y, 2009
23Awasthi S, 2000
24Leu TH, 2003
25Liu M, 2010
26Jung Y, 2007
27Sahoo BK, 2009
28Sui Z, 1993
29Mazumder A, 1995
30Hu, 2010
31Jung KH, unpublished
32Dairaku I, 2010
33Liu Y, 2008
34Jankun J, 2006
35Wang SS, 2009
36Kulkarni SK, 2008
37Gradisar H, 2007
38Wortelboer HM, 2003
39Gupta KK, 2006
40Nafisi S, 2009
41Sahoo BK, 2009
42Ji HF, 2009
43Hafner-Bratkovic I, 2008
44Chearwae W, 2004
45Marcu MG, 2006
46Jutooru I, 2010
47Martin-Cordero C, 2003
48Fang J, 2005
49Pullakhandam R, 2009
50Mullally JE, 2002
51Shen L, 2009
Curcumin
Interactors
Curcumin
Interactors
AChE1
ALR26
ATPase8
αS1-Casein7
β-amyloid9
BSA11
Bcl-210
Casein14
COX-216
CD13-AN15
DNA polIλ18
Fibrinogen19
GSH23FAK24GST-P121
GLO125 GSK-3β22
HIV-1IN29
Her226
Lysozyme35
HIV-1&2 PR28
DNA& RNA40
Pgp44
PhK3
PrP43
PKA3
Pp60-srcTK3
RNase A41
HSA27
IMPDH32
IVIG33
MDP-237
LOX34
MRP 1,238
TrxR48
Microtubulin39
Topo-II47TTR49
XO51UIP50
MAO36
Fe2+17
Cu2+17
Zn2+17
Mn2+5
cPK3
PfATP642
AGP2
Docking studies
p30045
ICDH31
Ca2+/CalM12
FtsZ20
Sp46
CAIs13
17β-HSD330
AKR1B104
Kim 11-03-2010
Curcumin binders
Targeting inflammation-induced obesity and metabolic
diseases by curcumin and other nutraceuticals.
Aggarwal BB. Annual Review Nutrition 2010 Aug 21;30:173-99.
Evidence that curcumin is an orally
bioavailable TNF-a blocker in human
Usharani,
2008
Placebo
Curcumin(150 mgx2 daily)
TN
F-a
(pg
/ml)
6.0
4.0
2.0
0.0
Pre Post
6.0
4.0
2.0
0.0
8 wks
N=21
N=23
Se
rum
TN
F-a
(pg
/ml)
To date, more than 65 human
clinical trials of curcumin,
which included more than 1000
patients, have been completed,
and as many as 35 clinical
trials are underway!
Therapeutic Role of Curcumin:
Lessons Learned from Clinical trials
60
0
10
20
30
40
50
5
10
52
Pu
bli
cati
on
s (
#)
1937-
1990
1991-
2000
2001-
July 2012
Gupta, Patchva and Aggarwal:
AAPS J. (in press)
Curcumin Clinical Trials?
Inflammatory diseases• Crohn disease
• Ulcerative proctitis
• Ulcerative colitis
• Inflammatory bowel disease
• Irritable bowel syndrome
•Rheumatoid arthritis
• Osteoarthritis
• Chronic anterior uveitis
• Recurrent anterior uveitis
•Post operative Inflammation
• Gastric ulcer
• Peptic ulcer
• H. pylori infection
• Idiopathic orbital inflammatory
Pseudotumor
Skin diseases• Vitiligo
• Psoriasis
Neurodegenerative diseases• Dejerine-Sottas disease
• Alzheimer's disease
Cardiovascular diseases• Acute coronary syndrome
• Atherosclerosis
Metabolic diseases• Diabetes
• Diabetic nephropathy
• Diabetic microangiopathy
• Lupus nephritis
Renal diseases• Renal transplantation
Viral diseases• Acquired immunodeficiency
syndromeOTHERS• -Thalassemia
• Biliary dyskinesia
• Gallbladder contraction
• Recurrent respiratory tract
infections
• Cholecystitis
• Hepatoprotection
• Chronic arsenic exposure
• Alcohol intoxication
• Chronic bacterial prostatitis
O O
H3CO
HO
OCH3
OH
Curcumin
Cancer• Colorectal cancer
• Pancreatic cancer
• Breast cancer
• Prostate cancer
• Multiple myeloma
• Lung cancer
• Cancer lesions
• Head and neck cancer
Gupta, Patchva and Aggarwal:, AAPS J. (in
press)
• Panahi, 2015
• Panahi, 2014
• Lopresti, 2014
• Nakayama, 2014
• Henrotin, 2014
• Panahi, 2014
• Ganjali, 2014
• Abidi, 2014
• Kuptniratsaikul, 2014
• Soare, 2014
• Panahi, 2014
• Klickovic, 2014
• Takahashi, 2014
• Jager, 2014
• Singla, 2014
• Sanmukhani, 2014
• Belcaro, 2014
• Cheungsamarn, 2014
• Basu, 2013
• Hejazi, 2013
• Morimoto, 2013
• Marciani, 2013
• Moreillon, 2013
• Ryan, 2013
• Elad, 2013
• Bergman, 2013
• Peek, 2013
• Kanai, 2013
• Muglikar, 2013
• Mohammadi, 2013
• Suskind, 2013
• Sahebkar, 2013
• Na, 2013
• Vaolak, 2013
• Irving, 2013
• Ledda, 2012
• Steigerwalt, 2012
• Akazawa, 2012
• Panahi, 2012
• Kudva, 2012
• DiSilvestro, 2012
• Cheungsamarn, 2012
• He, 2012
• Wongharoen, 2012
• Golombick, 2012
• Sugawara, 2012
• Chandran, 2012
• Vitaglione, 2012
• Chainani-Wu, 2012
• Kusuhara, 2012
• Araujo, 2012
• Pinsornsak, 2012
• Wolff, 2012
• Panahi, 2012
• Chainani-Wu, 2012
• Khajehdehi, 2012
• Kanai, 2012
• Appendino, 2011
• Mishra, 2011
• Pungcharoenkul,
2011
• Agarwal, 2011
• Khajehdehi, 2011
• Sasaki, 2011
• Cuomo, 2011
• Carroll, 2011
• Aggarwal, 2011
• Kanai, 2011
• He, 2011
• Belcaro, 2010
• Asawanonda, 2010
• Ide, 2010
• Sannia, 2010
• Koosirirat, 2010
• Dominiak, 2010
• Biswas, 2010
• Bayet-Robert, 2010
• Kalpravidh, 2010
• Burns, 2009
• Golonbick, 2009
• Masouni, 2009
• Cai, 2009
• Shimouchi, 2009
• Alsi, 2008
• Adhvaryu, 2008
• Dhillon, 2008
• Usharani, 2008
• Vareed, 2008
• Kurd, 2008
• Baum, 2007
• Chainani-Wu, 2007
• Di Mario, 2007
• Marczylo, 2007
• Everett, 2007
• Juan, 2007
• Tuntipopipat, 2006
• Hanai, 2006
• Cruz-Correa, 2006
• Loa, 2006
• Durgaprasad, 2005
• Shoskes, 2005
• Holt, 2005
• Ringman, 2005
• Garcea, 2005
• Sharma, 2004
• Bao, 2003
• Rasyid, 2002
• Plummer, 2001
• Cheng, 2001
• Sharma, 2001
• Heng, 2000
• Ramirez Bosca, 2000
• Niederau, 1999
• Lal, 1999
• Rasyid, 1999
• Shoba, 1998
• James, 1996
• Satoskar, 1986
• Deodhar, 1980
• Pilz, 1975
Curcumin Clinical Trials (120)
• https://ClinicalTrials.gov/show/NCT
01811381
• https://ClinicalTrials.gov/show/NCT
01246973
• https://ClinicalTrials.gov/show/NCT
01294072
• https://ClinicalTrials.gov/show/NCT
02300727
• https://ClinicalTrials.gov/show/NCT
01982734
• https://ClinicalTrials.gov/show/NCT
01383161
• https://ClinicalTrials.gov/show/NCT
01925287
• https://ClinicalTrials.gov/show/NCT
02476708
• https://ClinicalTrials.gov/show/NCT
01543386
• https://ClinicalTrials.gov/show/NCT
00927485
• https://ClinicalTrials.gov/show/NCT
01179256
• https://ClinicalTrials.gov/show/NCT
01052025
• https://ClinicalTrials.gov/show/NCT
01975363
• https://ClinicalTrials.gov/show/NCT
00365209
• https://ClinicalTrials.gov/show/NCT
00641147
• https://ClinicalTrials.gov/show/NCT
02321293
• https://ClinicalTrials.gov/show/NCT
01035580
• https://ClinicalTrials.gov/show/NCT
02298985
• https://ClinicalTrials.gov/show/NCT
02104752
• https://ClinicalTrials.gov/show/NCT
01403545
• https://ClinicalTrials.gov/show/NCT
02064673
• https://ClinicalTrials.gov/show/NCT
02064673
• https://ClinicalTrials.gov/show/NCT
00895167
• https://ClinicalTrials.gov/show/NCT
01333917
• https://ClinicalTrials.gov/show/NCT
01875822
• https://ClinicalTrials.gov/show/NCT
02474953
• https://ClinicalTrials.gov/show/NCT
01042938
• https://ClinicalTrials.gov/show/NCT
01201694
• https://ClinicalTrials.gov/show/NCT
01514370
• https://ClinicalTrials.gov/show/NCT
01917890
• https://ClinicalTrials.gov/show/NCT
01490996
• https://ClinicalTrials.gov/show/NCT
01001637
• https://ClinicalTrials.gov/show/NCT
02255370
• https://ClinicalTrials.gov/show/NCT
02369549
• https://ClinicalTrials.gov/show/NCT
00113841
• https://ClinicalTrials.gov/show/NCT
00779493
• https://ClinicalTrials.gov/show/NCT
00181662
• https://ClinicalTrials.gov/show/NCT
01925547
• https://ClinicalTrials.gov/show/NCT
01608139
• https://ClinicalTrials.gov/show/NCT
01052597
• https://ClinicalTrials.gov/show/NCT
01330810
• https://ClinicalTrials.gov/show/NCT
02439385
• https://ClinicalTrials.gov/show/NCT
01859858
• https://ClinicalTrials.gov/show/NCT
00164749
• https://ClinicalTrials.gov/show/NCT
02277223
• https://ClinicalTrials.gov/show/NCT
02100423
• https://ClinicalTrials.gov/show/NCT
00889161
• https://ClinicalTrials.gov/show/NCT
00745134
• https://ClinicalTrials.gov/show/NCT
00969085
• https://ClinicalTrials.gov/show/NCT
01740323
• https://ClinicalTrials.gov/show/NCT
01225094
• https://ClinicalTrials.gov/show/NCT
00595582
• https://ClinicalTrials.gov/show/NCT
00973869
• https://ClinicalTrials.gov/show/NCT
00528151
• https://ClinicalTrials.gov/show/NCT
01514266
• https://ClinicalTrials.gov/show/NCT
02281981
• https://ClinicalTrials.gov/show/NCT
01160302
• https://ClinicalTrials.gov/show/NCT
01968564
• https://ClinicalTrials.gov/show/NCT
00689195
• https://ClinicalTrials.gov/show/NCT
01964846
• https://ClinicalTrials.gov/show/NCT
01750359
• https://ClinicalTrials.gov/show/NCT
00094445
• https://ClinicalTrials.gov/show/NCT
02152475
• https://ClinicalTrials.gov/show/NCT
00475683
• https://ClinicalTrials.gov/show/NCT
00752154
• https://ClinicalTrials.gov/show/NCT
00099710
• https://ClinicalTrials.gov/show/NCT
01022632
• https://ClinicalTrials.gov/show/NCT
01320436
• https://ClinicalTrials.gov/show/NCT
01928043
• https://ClinicalTrials.gov/show/NCT
01489592
• https://ClinicalTrials.gov/show/NCT
01909037
• https://ClinicalTrials.gov/show/NCT
02018328
• https://ClinicalTrials.gov/show/NCT
01288859
• https://ClinicalTrials.gov/show/NCT
00192842
• https://ClinicalTrials.gov/show/NCT
02494141
• https://ClinicalTrials.gov/show/NCT
00247026
• https://ClinicalTrials.gov/show/NCT
00248053
• https://ClinicalTrials.gov/show/NCT
00542711
• https://ClinicalTrials.gov/show/NCT
01269203
• https://ClinicalTrials.gov/show/NCT
00295035
• https://ClinicalTrials.gov/show/NCT
01167673
• https://ClinicalTrials.gov/show/NCT
01831193
• https://ClinicalTrials.gov/show/NCT
01712542
• https://ClinicalTrials.gov/show/NCT
02337192
• https://ClinicalTrials.gov/show/NCT
02095717
• https://ClinicalTrials.gov/show/NCT
01048983
• https://ClinicalTrials.gov/show/NCT
01948661
• https://ClinicalTrials.gov/show/NCT
02138955
• https://ClinicalTrials.gov/show/NCT
00768118
• https://ClinicalTrials.gov/show/NCT
00027495
• https://ClinicalTrials.gov/show/NCT
00486460
• https://ClinicalTrials.gov/show/NCT
02017353
• https://ClinicalTrials.gov/show/NCT
00176618
• https://ClinicalTrials.gov/show/NCT
01285375
• https://ClinicalTrials.gov/show/NCT
00525421
• https://ClinicalTrials.gov/show/NCT
00792818
• https://ClinicalTrials.gov/show/NCT
00793130
• https://ClinicalTrials.gov/show/NCT
01344291
• https://ClinicalTrials.gov/show/NCT
00118989
• https://ClinicalTrials.gov/show/NCT
00003365
• https://ClinicalTrials.gov/show/NCT
01029327
• https://ClinicalTrials.gov/show/NCT
02099890
• https://ClinicalTrials.gov/show/NCT
01647412
• https://ClinicalTrials.gov/show/NCT
02445651
• https://ClinicalTrials.gov/show/NCT
00235625
• https://ClinicalTrials.gov/show/NCT
01716637
• https://ClinicalTrials.gov/show/NCT
02442453
• https://ClinicalTrials.gov/show/NCT
02251678
• https://ClinicalTrials.gov/show/NCT
02251678
• https://ClinicalTrials.gov/show/NCT
02336087
• https://ClinicalTrials.gov/show/NCT
01906840
• https://ClinicalTrials.gov/show/NCT
01646047
• https://ClinicalTrials.gov/show/NCT
01752868
• https://ClinicalTrials.gov/show/NCT
02088307
• https://ClinicalTrials.gov/show/NCT
02369536
• https://ClinicalTrials.gov/show/NCT
00799630
• https://ClinicalTrials.gov/show/NCT
02413099
• https://ClinicalTrials.gov/show/NCT
00219882
Curcumin Clinical Trials- Links
Loeber C.C.. De curcuma officinarum. & c., Halae . 1748.Shortt T.. Madras quart. J. med. Sci. 1867; 12: 170.
Guttenberg A.. Z. ges. exp. Med. 1927; 54: 542.
Koch R.. Münch. med. Wschr. 1927; 74: 972.
Kalk H., Nissen K.. Dtsch. med. Wschr. 1931; 62: 1613.
Fähndrich H.A.. Fortschr. Ther. 1932; 8: 606.
Franquelo E.. Münch. med. Wschr. 1933; 80: 524.
Henning N., Künzel O.. Münch. med. Wschr. 1934; 81: 1611.
Potter van Loon J.. Geneesk. Tijdschr. van Ned.-Ind. 1934; 74: 782.
von den Velden R.. Fortschr. Ther. 1934; 10: 725.
Helmy W.. Med. Welt 1935; 9: 90.
Stefan, R. (1934) Quoted by Vetterlein.
Vetterlein S.. Dtsch. med. Wschr. 1935; 61: 964.
TURMERIC (CURCUMIN) IN BILIARY DISEASES
Albert Oppenheimer M.D.
(ASSISTANT PROFESSOR OF ROENTGENOLOGY TO THE AMERICAN UNIVERSITY OF BEIRÛT, LEBANON)
The Lancet, Volume 229, Issue 5924, Pages 619 - 621, 13 March 1937
Curcumin
Bioavailability
Biodistribution of [ 125I]6 Curcumin in normal mice
Cu
rcu
min
level (I
D/g
)
Time (min)Ryu, 2006
Add spice to
your life, not
years to your
life!
Glu
tath
ion
e-S
-tra
ns
fera
se
(nm
ol/m
in/m
g p
rote
in)
100
75
50
25
0
Curcumin (36 mg/day)
Pre Post
N = 15
Ingestion of 440 mg
of Curcuma extract (36
mg curcumin) for 29
days was
accompanied by a
59% decrease in
lymphocytic
glutathione S-
transferase activity.
At higher dose levels,
this effect was not
observed.
Effects of dietary curcumin on glutathione S-transferase in
lymphocytes from patients with colorectal cancer
Sharma et al., 2001, Clinical Cancer Research
Combination treatment with curcumin and quercetin of
adenomas in familial adenomatous polyposis
50
40
30
20
10
0
8
6
4
2
0Pre
Po
lyp
siz
e (
mm
)
Po
lyp
nu
mb
er
N = 5
Post
Curcumin (1440 mg/day)
Post
Cruz-Correa et al., 2006, Clinical Gastroenterology Hepatology
After six
months, the
mean percent
decrease in the
number and
size of polyps
from baseline
was 60.4%
and 50.9%,
respectively.
Pre
Curcumin maintenance therapy for ulcerative colitis:
randomized, multicenter, double-blind, placebo-controlled trial.
50
40
30
20
10
0
Rec
urr
en
ce
RecurrencePlacebo
Curcumin (2000 mg/day)
N = 82
RecurrencePlacebo
6 months
Hanai et al., 2006, Clinical Gastroenterology Hepatology
Eighty-nine patients with quiescent UC
were recruited.
Forty-five patients received curcumin,
1g after breakfast and 1g after the
evening meal, plus sulfasalazine (SZ) or
mesalamine, and 44 patients received
placebo plus SZ or mesalamine for 6
months.
Of 43 patients who received curcumin,
2 relapsed during 6 months of therapy ,
whereas 8 of 39 patients in the placebo
group relapsed.
Furthermore, curcumin improved both
CAI (P=.038) and EI (P=.0001), thus
suppressing the morbidity associated
with UC.
A 6-month follow-up was done during
which patients in both groups were on
SZ or mesalamine.
Curry for the cure?
Inflammatory Bowel Disease. 2007
2/43
8/39
Sulfasalazine/mesalamine +/- Curcumin
Phase IIa clinical trial of curcumin for the
prevention of colorectal neoplasia
25
20
15
10
5
02000 4000
Ab
err
an
t c
ryp
t fo
ci
(#)
Baseline
Curcumin (mg/day)
N = 44
Baseline
Carroll et al., 2011, Cancer Prevention
Research
Forty-one subjects
completed the study
(30 days).
Neither dose of curcumin
reduced PGE₂ or 5-HETE
within ACF or normal
mucosa or reduced Ki-67
in normal mucosa.
A significant 40%
reduction in ACF number
occurred with the 4-g
dose, whereas ACF were
not reduced in the 2-g
group
A pilot study of the antioxidant effect of
curcumin in tropical pancreatitis.
15
10
5
0
Ma
lon
dia
lde
hy
de
(nm
ol/
gm
Hb
)
Glu
tath
ion
e
(nm
ol/
gm
Hb
)
10
8
6
4
2
0
Placebo
N = 20
Curcumin (mg/day)
1500 1500Placebo
Durgaprasad et al., 2005, Indian Journal Medical Research
MDA and GSH
levels in
patients with
tropical
pancreatitis
after oral
administration
of curcumin
for 6 weeks
Combined inhibitory effects of soy isoflavones and
curcumin on the production of prostate-specific antigen
Ide et al., 2010, Prostate.
10
8
6
4
2
0
PSA <10 ng/ml
40
30
20
10
0
PSA ≥10 ng/ml
Pro
sta
te s
pe
cif
ic a
nti
ge
nN = 85
Curcumin (100 mg/day)
Placebo Curcumin
Serum PSA levels at
the baseline (pre) and
after administration
of isoflavones
(40 mg/day) and
curcumin
(100 mg/day)
supplements or
placebo (post)
for 6 months in
participants with PSA
< 10 or
PSA ≥ 10
Effect of turmeric oil and turmeric oleoresin on cytogenetic damage in
patients suffering from oral submucous fibrosis.
Hastak et al., 1997, Cancer Lett .
12
10
8
6
4
2
0
Mic
ron
uc
lei
cell
s
N = 58
Pre
3 months
Patients suffering from
submucous fibrosis were
given a total oral dose of
turmeric oil (600 mg TO
mixed with 3 g turmeric/day).
Turmeric oleoresin (600 mg +
3 g turmeric/day) and 3 g
turmeric/day as a control for
3 months.
It was observed that all three
treatment modalities
decreased the number of
micronucleated cells both in
exfoliated oral mucosal cells
and in circulating
lymphocytes.
Turmeric oleoresin was
found to be more effective in
reducing the number of Mn
in oral mucosal cells, but in
circulating lymphocytes the
decrease in Mn was
comparable in all three
groups.
Turmeric
(3g)+ TO
Turmeric
(3g)+ TOR
Turmeric
(3g)
Effect of turmeric on urinary mutagens
in smokers.Polasa K, Raghuram TC, Krishna TP, Krishnaswamy K.
Mutagenesis. 1992 Mar;7(2):107-9.
National Institute of Nutrition, Jamai-osmania, Hyderabad, India.
Curcumin, the active principle of turmeric, is known to act as an anti-oxidant,
anti-mutagen and anti-carcinogen in experimental animals. In the present
study, anti-mutagenic effects of turmeric were assessed in 16 chronic
smokers.
It was observed that turmeric, given in doses of 1.5 g/day for 30 days,
significantly reduced the urinary excretion of mutagens in smokers.
In contrast, in six non-smokers, who served as control, there was no change in
the urinary excretion of mutagens after 30 days.
Turmeric had no significant effect on serum aspartate aminotransferase and
alanine aminotransferase, blood glucose, creatinine and lipid profile.
These results indicate that dietary turmeric is an effective anti-mutagen and it
may be useful in chemoprevention.
p53Apoptosis
Curcumin & CRC patients 126 pts; 360 mg curcumin; thrice/day
(He et al, 2011)
TNF-aBody weight
29 patients with asymptomatic, relapsed, or plateau phase multiple myeloma.
Curcumin was given either alone (orally at 2, 4, 6, 8, or 12 g/d in two divided doses) or in combination with bioperine
(10 mg in two divided doses) for 12 weeks.
Peripheral blood mononuclear cells from 28 patients examined at baseline showed constitutively active NF-κB, COX-
2, and STAT3.
Furthermore, oral administration of curcumin was associated with significant down-regulation in the constitutive
activation of NF-κB and STAT3, and it suppressed COX-2 expression in most of the patients. These observations
suggest the potential of curcumin against multiple myeloma.
Curcumin downregulates NF-КB and related
genes in patients with multiple myeloma:
Results of a phase 1/2 study.
Vadhan-Raj S, Weber D, Wang M, Giralt S, Alexanian R,
Thomas S, …Aggarwal BB
Blood
2007;110(11):357a.
Constitutive activation of NF-kB in PBMC from MM Patients
and its Suppression by Curcumin (2g/day)
NF-kB
- + - + - + - + - + TNF
Pre 4wPatient #4
(482480)
8w 12w 20w
Patient #6
(337641)
NF-kB
- + - + - + - + - + TNF
4wPre 12w 16w 20w
A, B, C, D, E, F, and G represents Pre, 4, 8, 12, 16, 20 and 24 wks after curcumin administration
•The only FDA-approved therapies- gemcitabine and erlotinib- produce objective responses in less than 10% of
patients.
•The objectives of this trial were to evaluate the toxicity and activity of curcumin, as well as its impact on survival
and biologic correlates.
•Patients were treated with 8 grams of curcumin (Sabinsa Corp.) daily by mouth for two months and evaluated
radiographically using the RECIST criteria.
•Maintenance therapy was continued at the same dose and schedule until disease progression.
•RESULTS: Seventeen patients were enrolled as of the date of analysis.
•Six were inevaluable: noncompliance (n=1), never dosed (n= 1), noted to have gastric obstruction after one dose
(n=1), and too early (n=3).
•Eleven patients were evaluable for response and 15 were evaluable for toxicity.
•To date, four patients have stable disease (2+, 2+, 3+ and 7 months) and one patient had a brief partial
remission (73% reduction in tumor size by RECIST) that lasted one month.
•No toxicity was observed. Serum was available for evaluation of pre-and post-dose cytokine levels in thirteen
patients. Interestingly, the patient with the partial remission had marked increases in (4-35 fold) in serum IL-1
receptor antagonist, IL-6, IL-10 and IL-8 levels. One to three other patients also had post-treatment increases one
or more of the above cytokines, albeit to a lesser extent (2-6 folds).
•CONCLUSIONS: We conclude that curcumin is well tolerated and our preliminary results
suggest biologic activity in pancreatic cancer.From ASCO-2006
Phase II Trial of Curcumin in Patients with
Advanced Pancreatic CancerN. Dhillon, B. B. Aggarwal, R. A. Wolff, J. L. Abbruzzese, D. S. Hong, L. H. Camacho, L. Li, F. S.Braiteh, R. Kurzrock
A Gift of Time"If you want to do something, do it now. Don't wait."
This advice come from a patient with end-stage pancreatic
cancer who was given an unexpected gift of time, thanks to
curcumin, the main ingredient in the spice tumeric. When
Duane Jacobson first came to the Clinical Center for Targeted
Therapy (CCTT) at M. D. Anderson, he had less than three
months to live, estimated his oncologist Razelle Kurzrock,
M.D., principal investigator of the curcumin trial and also chair
of the Department of Investigational Cancer Therapeutics
(Phase I Clinical Trials Program). More than two years later,
he is traveling around the world with his wife Hildrud while
enrolled in an NIH-sponsored, phase II clinical trial of
curcumin in advanced pancreatic cancer.
Phase II trial of curcumin in patients
with advanced pancreatic cancer.
Dhillon N, Aggarwal BB, Newman RA, Wolff RA,
Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V,
Kurzrock R.
Clin Cancer Res.
2008 Jul 15;14(14):4491-9.
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Valproic acid
Prof. S. Konstantinov, MD PhD; Medical University, Faculty of Pharmacy
Dept. of Pharmacology, Pharmacotherapy and Toxicology; Lab for Experimental Chemotherapy; 2 Dunav Str, 1000
Sofia, Bulgaria; Spiro Mihaylov Konstantinov konstantinov.spiromihaylov@gmail.com
Curcumin &
Arthritis
Clinical Trials
Randomized, Pilot Study to Assess the Efficacy and Safety of
Curcumin in Patients with Active Rheumatoid Arthritis
10
8
6
4
2
0C-R
eacti
ve P
rote
in (
mg
/l)
N = 45
Curcumin
(500 mg/day)Baseline
8 wks
Diclofenac +/- CurcuminLevels of C-reactive protein in
patients with active rheumatoid
arthritis at baseline and after
curcumin treatment
Forty-five patients diagnosed with RA
were randomized into three groups with
patients receiving curcumin (500 mg)
and diclofenac sodium (50 mg) alone or
their combination.
The primary endpoints were reduction in
Disease Activity Score (DAS) 28.
The secondary endpoints included
American College of Rheumatology
(ACR) criteria for reduction in
tenderness and swelling of joint scores.
Patients in all three treatment groups
showed statistically significant changes
in their DAS scores.
Interestingly, the curcumin group
showed the highest percentage of
improvement in overall DAS and ACR
scores (ACR 20, 50 and 70) and these
scores were significantly better than the
patients in the diclofenac sodium group.
Chandran and Goel, 2012, Phytother Res
Efficacy and safety of curcumin-phosphatidylcholine complex, during
extended administration in osteoarthritis patients
200
150
100
50
0
0 8 12 0 8 12
C-
Rea
cti
ve p
rote
in
(mg
/L)
Curcumin
(200 mg/day)
N = 50
Weeks
Control 3 months
After three months of
treatment, the global
WOMAC score decreased by
58%, walking distance in the
treadmill test was prolonged
from 76 m to 332 m, and
CRP levels decreased from
168 +/- 18 to 11.3 +/-. 4.1
mg/L in the subpopulation
with high CRP.
In comparison, the control
group experienced only a
modest improvement in
these parameters (2% in the
WOMAC score, from 82 m to
129 m in the treadmill test,
and from 175 +/- 12.3 to 112
+/- 22.2 mg/L in the CRP
plasma concentration),
while the treatment costs
(use of anti-inflammatory
drugs, treatment and
hospitalization) were
reduced significantly in the
treatment group.
Belcaro et al., 2010, Panminerva Med
Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex,
during extended ( 8 months) administration in osteoarthritis patients
50
40
30
20
10
0
WO
MA
C s
co
re
400
300
200
100
0
Tre
ad
mil
l te
st
1.5
1.0
0.5
0
IL-6
(p
g/m
L)
1.0
0.8
0.6
0.4
0.2
0
IL-1
β(p
g/m
L)
3
2
1
0
sC
D4
0L
(n
g/m
L)
40
30
20
10
0
Ery
thro
cy
te
se
dim
en
tati
on
ra
te
(mm
/hr)
Pre Post
N = 100Curcumin (200 mg/day)
TreatmentControl
Belcaro et al., 2010, Alternate Medicine Review
The treatment consisted of two
500-mg tablets daily, one after
breakfast and one after dinner
(1,000 mg/day, corresponding to
200 mg curcumin/ day).
The composition of the test
material was a natural curcuminoid
mixture (20%), phosphatidyl-
choline (40%), and microcrystalline
cellulose (40%).
The composition of the
curcuminoid mixture was
75% curcumin,
15% demethoxycurcumin, and
10% bisdemethoxycurcumin.
Curcumin &
Psoriasis
Clinical Trials
Treatment of psoriasis
with Psoria-Gold
After4 weeks
Before
R Knee L Knee L Leg L Elbow
12-05-2003
11-07-2003
Courtesy of Dr. Madeline Heng from UCLA
http://www.psoria-gold.com/RESEARCH.html
MCY Heng, MK Song, J. Harker and MK Heng, Br. J. Dermatology, 143, 2000, 937-949
Drug-induced suppression of phosphorylase kinase activity correlates
with resolution of psoriasis as assessed by clinical, histological and
immunohistochemical parameters.
1600
1200
800
400
0Ph
osp
ho
ryla
se k
inase
(Un
its/m
g p
rote
in)
Vehicle Curcumin
N = 12
1 % in gel
4 weeks
Heng et al., 2000, British Journal Dermatology
Eelevated PhK activity correlates with psoriatic
activity. PhK activity was assayed in four groups,
each with 10 patients:
(i) active untreated psoriasis;
(ii) resolving psoriasis treated by calcipotriol, a
vitamin D3 analogue and an indirect inhibitor
of PhK;
(iii) curcumin, a selective PhK inhibitor;
(iv) 10 normal non-psoriatic subjects.
PhK activity in units mg-1 protein was highest in
active untreated psoriasis (1204 +/- 804.3; mean
+/- SD), lower in the calcipotriol-treated group
(550.7 +/- 192. 9), lower in curcumin-treated group
(207.2 +/- 97.6), and lowest in normal skin (105.4
+/- 44.6).
One-way analysis of variance performed on log-
transformed PhK activity measure showed
significant differences among the four groups,
F3,36 = 48.79, P < 0.0001.
Our results demonstrate that drug-induced
suppression of PhK activity is associated with
resolution of psoriatic activity
Curcumin & Skin DiseasesCurcumin-induced suppression of phosphorylase kinase activity
correlates with resolution of psoriasis as assessed by clinical,
histological and immunohistochemical parameters
MCY Heng, MK Song, J. Harker and MK Heng,
Br. J. Dermatology, 143, 2000, 937-949
Psoriasis,
Actinic keratosis,
Acne,
Warts,
Dermatitis,
Eczema
Wound healing,
Sunburn,
Skin cancer
UveitisUveitis is the inflammation of uvea.
Symptoms include red eye, injected conjunctiva, pain and decreased
vision.
Uveitis is estimated to be responsible for approx 10% of the blindness in
the USA
Treated with steroids, topical cycloplegics, such as atropine or
homatropine, methotrexate, anti-TNFs' infusions.
Management of chronic anterior uveitis
relapses: efficacy of oral phospholipidic
curcumin treatment. Long-term follow-up.
Allegri P, Mastromarino A, Neri P. Genova, Italy.
Clin Ophthalmol. 2010 Oct 21;4:1201-6.
Administered 600 mg curcumin, twice a day, orally.
Consisted of 106 patients.
More than 80% of patients responded.
Benefits in eye inflammatory and degenerative conditions,
such as dry eye, maculopathy, glaucoma, and diabetic
retinopathy.
Pts with relapse
No of relapse
Management of chronic anterior uveitis relapses:
efficacy of oral phospholipidic curcumin treatment. Long-term follow-up.
120
100
80
60
40
20
0Rela
pse (
# p
ts) 300
200
100
0To
tal re
lap
se n
um
ber
Pre
Post
N = 106 pts; 12 months follow up
Curcumin
(120 mg/day)
Meriva, 600 mg/day X2
group 1 (autoimmune
uveitis),
group 2 (herpetic uveitis),
group 3 (different
etiologies of uveitis).
The primary end point of
our work was the
evaluation of relapse
frequency in all treated
patients, before and after
Norflo treatment, followed
by the number of relapses
in the three etiological
groups.
The secondary end points
were the evaluation of
relapse severity and of the
overall quality of life.
The results showed that
Norflo was well tolerated
and could reduce eye
discomfort symptoms and
signs after a few weeks of
treatment in more than
80% of patients.
Allegri et al., 2010, Clinical Ophthalmology
Indicates therapeutic role of curcumin and its efficacy in eye relapsing diseases, such as anterior
uveitis, and points out other promising curcumin-related benefits in eye inflammatory and degenerative
conditions, such as dry eye, maculopathy, glaucoma, and diabetic retinopathy.
Valproic acid
Prof. S. Konstantinov, MD PhD; Medical University, Faculty of Pharmacy
Dept. of Pharmacology, Pharmacotherapy and Toxicology; Lab for Experimental Chemotherapy; 2 Dunav Str, 1000
Sofia, Bulgaria; Spiro Mihaylov Konstantinov konstantinov.spiromihaylov@gmail.com