Curcumin - nebula.wsimg.com

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


• 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


• 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


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01294072


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01383161


01925287


02476708


01543386


00927485


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01035580


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02104752


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02064673


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00895167


01333917


01875822


02474953


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01201694


01514370


01917890


01490996


01001637


02255370


02369549


00113841


00779493


00181662


01925547


01608139


01052597


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02439385


01859858


00164749


02277223


02100423


00889161


00745134


00969085


01740323


01225094


00595582


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01514266


02281981


01160302


01968564


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01964846


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02152475


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00099710


01022632


01320436


01928043


01489592


01909037


02018328


01288859


00192842


02494141


00247026


00248053


00542711


01269203


00295035


01167673


01831193


01712542


02337192


02095717


01048983


01948661


02138955


00768118


00027495


00486460


02017353


00176618


01285375


00525421


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00118989


00003365


01029327


02099890


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02445651


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02251678


02251678


02336087


01906840


01646047


01752868


02088307


02369536


00799630


02413099


00219882

Curcumin Clinical Trials- Links

https://clinicaltrials.gov/show/NCT01811381






















































































































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


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


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


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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BBABBA

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 [email protected]

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 [email protected]

Curcumin - nebula.wsimg.com

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