Plant-derived health - The effects of turmeric and curcuminoids

Abstract

Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.

Full text

273
Revisión
Plant-derived health - the effects of turmeric and curcuminoids
S. Bengmark1, M.ª D. Mesa2, and A. Gil2
1Institute of Hepatology University College London Medical School. 69-75 Chenies Mews London. 2Departamento de Bioquímica
y Biología Molecular II. Instituto de Nutrición y Tecnología de Alimentos. “José Mataix”. Universidad de Granada. Granada.
España.
Nutr Hosp. 2009;24(3):273-281
ISSN 0212-1611 • CODEN NUHOEQ
S.V.R. 318
EFECTOS SALUDABLES DE LA CÚRCUMA
Y DE LOS CURCUMINOIDES
Resumen
Las plantas contienen un gran número de sustancias de
naturaleza polifenólica con capacidad para reducir los
procesos inflamatorios y, por lo tanto, incrementar la
resistencia a determinadas enfermedades. Ejemplos de
algunos polifenoles son los isotiocianatos presentes en la
col y el brócoli, epigalocatequinas del té verde, capsaicina
de las guindillas, chalonas, rutina y naringenina de las
manzanas, resveratrol del vino tinto y de los cacahuetes, y
curcumina y curcuminoides de la cúrcuma. La mayoría
de las enfermedades tienen un componente discreto pero
obvio de inflamación sistémica. Muchos trabajos han
sugerido que los efectos de estos tratamientos podrían ser
mejorados tras la restricción de la ingesta de moléculas
proinflamatorias, como los productos avanzados de la gli-
cación (AGE) y lipoperoxidación (ALE), junto con la
suplementación de moléculas antiinflamatorias, como
algunos polifenoles obtenidos de las plantas. Concreta-
mente, los efectos de los curcuminoides y de su principal
componente, la curcumina, han sido ampliamente docu-
mentados. Esta revisión, recopila los datos actuales
acerca de las principales moléculas activas derivadas de
la cúrcuma, para las cuales se ha demostrado que poseen
una potente actividad antioxidante, inhiben la ciclooxige-
nasa 1 (COX-1), la lipoperoxidasa (LPO), el factor
nuclear NF-κB (NF-κB), así como los AGE. La mayoría
de los efectos han sido demostrados mediante estudios
experimentales; sin embargo, los estudios clínicos en
humanos son escasos. Se ha sugerido que la suplementa-
ción con curcuminoides podría ser interesante como un
complemento para los tratamientos farmacológicos, ade-
más de cómo tratamiento prebiótico en condiciones en las
que no existe una terapia eficaz, como en el caso de la
enfermedad de Crohn, en pacientes ingresados en Unida-
des de Cuidados Intensivos durante periodos prolonga-
dos, y también en patologías tales como el cáncer, la cirro-
sis hepática, la enfermedad renal crónica, la enfermedad
digestiva obstructiva, la diabetes y la enfermedad de Alz-
heimer. (Full spanish translation in www.nutricionhospi-
talaria.com).
(Nutr Hosp. 2009;24:273-281)
Palabras clave: Diabetes. Alzheimer. Cúrcuma. Curcumi-
noides.
Abstract
Plants contain numerous polyphenols, which have been
shown to reduce inflammation and hereby to increase
resistance to disease. Examples of such polyphenols are
isothiocyanates in cabbage and broccoli, epigallocatechin
in green tee, capsaicin in chili peppers, chalones, rutin and
naringenin in apples, resveratrol in red wine and fresh
peanuts and curcumin/curcuminoids in turmeric. Most
diseases are maintained by a sustained discreet but
obvious increased systemic inflammation. Many studies
suggest that the effect of treatment can be improved by a
combination of restriction in intake of proinflammatory
molecules such as advanced glycation end products
(AGE), advanced lipoperoxidation end products (ALE),
and rich supply of antiinflammatory molecules such as
plant polyphenols. To the polyphenols with a bulk of expe-
rimental documentation belong the curcuminoid family
and especially its main ingredient, curcumin. This review
summarizes the present knowledge about these turmeric-
derived ingredients, which have proven to be strong antio-
xidants and inhibitors of cyclooxigenase-2 (COX-2),
lipoxygenase (LOX) and nuclear factor κB (NF-κB) but
also AGE. A plethora of clinical effects are reported in
various experimental diseases, but clinical studies in
humans are few. It is suggested that supply of polyphenols
and particularly curcuminoids might be value as comple-
ment to pharmaceutical treatment, but also prebiotic tre-
atment, in conditions proven to be rather therapy-resis-
tant such as Crohn’s, long-stayed patients in intensive
care units, but also in conditions such as cancer, liver cirr-
hosis, chronic renal disease, chronic obstructive lung dise-
ase, diabetes and Alzheimer’s disease.
(Nutr Hosp. 2009;24:273-281)
Key words: Diabetes. Alzheimer’s disease. Turmeric.
Curcuminoids.
Correspondence: A. Gil Hernández.
Departamento de Bioquímica y Biología Molecular II.
Instituto de Nutrición y Tecnología de Alimentos.
Centro de Investigación Biomédica.
Avda. del Conocimiento, s/n.
18100 Armilla. Granada.
E-mail: agil@ugr.es
Recibido: 2-XI-2008.
Aceptado: 6-II-2009.

274 S. Bengmark et al.
Nutr Hosp. 2009;24(3):273-281
Introduction
Modern medicine has to a large extent failed in its
ambition to control both acute and chronic diseases.
Acute diseases have an unacceptably high morbidity
and co-morbidity. Furthermore, the world suffers an
epidemy of chronic diseases of a dimension never seen
before, and these diseases are now like a prairie fire
also spreading to so called developing countries. Chro-
nic diseases —including diseases such as cardiovascu-
lar and neurodegenerative conditions, diabetes, stroke,
cancers and respiratory diseases— constitute today
46% of the global disease burden and 59% of the global
deaths; each year on earth approximately 35 million
individuals will die in conditions related to chronic
diseases, and the numbers are increasing and have done
so for several years.1Similarly, the morbidity related to
advanced medical and surgical treatments and emer-
gencies, especially infectious complications, is also
fast increasing; sepsis is the most common medical and
surgical complication.
Accumulating evidence supports the association of
chronic diseases (ChDs) to modern life style: stress, lack
of exercise, abuse of tobacco and alcohol, and to the
transition from natural unprocessed foods to processed,
calorie-condensed and heat-treated foods. There is a
strong association between ChD and reduced intake of
plant fibres, plant antioxidants and increased consump-
tion of industrially produced and processed dairy pro-
ducts, refined sugars and starch products. Heating up
milk (pasteurization), and especially production of and
storage of milk powder, produces large amounts of
advanced glycation products (AGEs) and advanced
lipoxidation products (ALEs), known as potent inducers
of inflammation.2This information is especially impor-
tant as many foods such as ice cream, enteral nutrition
solutions and baby formulas are based on milk powder
and its derivatives. Bread, especially from gluten-con-
taining grains, is also rich in molecules with documented
pro-inflammatory effects, and bread crusts often used
experimentally to induce inflammation.3-5
Plant consumption-derived protection
Common to those suffering ChD as well as critical ill-
ness (CI) is that they suffer an increased degree of
inflammation, most likely due to their Western lifestyle.
We are increasingly aware that plant-derived substan-
ces, often referred to as chemopreventive agents, have
an important role to play in control of inflammation.
These substances are not only inexpensive, they are also
easy available, and have no or limited toxicity. Among
these numerous chemo-preventive agents are a whole
series of phenolic and other compounds believed to
reduced speed of aging and prevent degenerative mal-
functions of organs. For these reasons, the interest for
the study of these compounds has increased in the last
years. Among them, various curcuminoids found in tur-
meric curry foods and thousands more of hitherto less or
unexplored substances have received an increasing
attention for their strong chemo-preventive ability in
recent few years. Curcumin is the most explored of the
so called curminoids, a family of chemopreventive subs-
tances present in the spice turmeric. Although the subs-
tance has been known for some time, it is in the most
recent years that the interest has exploded, much in para-
llel with increasing concern for severe side-effects of
synthetic cyclooxigenase-2 (COX-2) inhibitors, marke-
ted by pharmaceutical industry. This review reported
mainly curcumin experimental and clinical studies focus
on curcumin and its effects (table I).
Table I
Curcuminoid main effects
Main mechanisms of action
Atherosclerosis ↓ LDL oxidation29,31; Cell membrane stabilisation30;
↑
antioxidant plasma concentrations31
Cancer Induces apoptosis36-45; Inhibits metastasis46
Diabetes ↓glucose, haemoglobin and glycated haemoglobin48;
↑
antioxidant protection48
Gastric diseases ↓growth of some Helicobacter strains49; ↓NF-κB and mitogenic response 50; Antifungic properties51
Hepatic diseases ↓lipid accumulation52-54; ↓hepatic risk biomarkers53,55; ↓NF-κB-dependent gene expression;
↓inflammatory molecules expression55,56; ↓oxidation55
Pancreatic diseases ↓NF-κB activation and activator protein 1 expression; ↓inflammatory molecules expression57;
↓caspase-3 activation57; ↓intra-pancreatic trypsin activation57
Intestinal diseases ↓lipid peroxidation58; ↓NF-κB activation58,60; ↓nitric oxide levels58; immune function regulation58;
↓MAPK p3859; ↓inflammatory response59,60
Neurodegenerative diseases Free radical scavenger66, 67; ↓oxidative markers70; ↓β-amyloid deposits 69
Ocular diseases Antioxidant activity77-79
Respiratory diseases ↓fibrogenesis80; inflammatory markers80; calcium and chloride pump alteration82,83; Anti-asthmatic effect84
Tobacco smoke-induced injury ↓NF-κB activation:↓anti-inflammatory molecules85

Turmeric and curcuminoids 275Nutr Hosp. 2009;24(3):273-281
Turmeric – approved as food additive
Curcumin, 1,7-bis (4-hydroxy-3-methoxyphenol)-
1,6heptadiene-3,5-dione), or dipheruloylquinone (fig. 1),
is the most abundant polyphenol present in the dietary
spice turmeric and received from dried rhizozomes of
the perennial herb Curcuma longa Linn, a member of
the ginger family. Turmeric is mainly known for its
excellent ability to preserve food, and is approved as
food additive in most Western countries. It is produced
in several Asian and South-American countries. Only
in India are about 500,000 metric tonnes produced each
year, of which about half is exported. It has, in addition
to extensive use as food additive, for generations also
been used in traditional medicine for treatment of
various external or internal inflammatory conditions
such as arthritis, colitis and hepatitis.
The molecule of curcumin resembles ubiquinols and
other phenols known to possess strong antioxidant acti-
vities. Its bioavailability on oral supplementation is
low, but can be improved by dissolution in ambivalent
solvents (glycerol, ethanol, DMSO).6It is also reported
to be dramatically elevated by co-ingestion of peperine
(a component of pepper), demonstrated both in experi-
mental animals and humans.7Polyphenols, isothiocya-
nates such as curcumin and flavonoids such as resvera-
trol, are all made accessible for absorption into the
intestinal epithelial cells and the rest of the body by
digestion/fermentation in the intestine by microbial
flora.8Several studies has demonstrated that curcumin
is atoxic, also in very high doses.9-10 It is estimated that
adult Indians consume daily 80-200 mg curcumin per
day.11 A common therapeutic dose is 400-600 mg cur-
cumin three times daily corresponding to up to 60 g
fresh turmeric root or about 15 g turmeric powder,
since the content of curcumin in turmeric is usually 4-
5%. Finally, it is noteworthy to mention that the treat-
ment of humans during three months with 8,000 mg
curcumin per day showed no side effects.10
Curcumin – an antioxidant and inhibitor of
NF-
κ
B, COX-2, LOX and iNOS and against
stress-induced overinflammation
NF-κB plays a critical role in several signal trans-
duction pathways involved in chronic inflammatory
diseases12 such as asthma and arthritis and various can-
cers.13 Activation of NF-κB is linked with apoptotic
cell death; either promoting or inhibiting apoptosis,
depending on cell type and condition. The expression
of several genes such as COX-2, lipoxygenase (LOX),
matrix mettaloproteinase-9 (MMP-9), inducible nitric
oxide synthase (iNOS), tumor necrosis factor alpha
(TNF-α), interleukin-8 (IL-8), eotaxin, cell surface
adhesion molecules and anti-apoptotic proteins are
regulated by NF-κB.14 COX-2 is inducible and barely
detectable under normal physiological conditions, but
is rapidly, but transiently, induced as an early response
to proinflammatory mediators and mitogenic stimuli
including cytokines, endotoxins, growth factors, onco-
genes and phorbol esters. COX-2 synthesizes series-2
prostaglandins (PGE2, PGF2-α), which contribute to
inflammation, swelling and pain. PGE2promotes pro-
duction of IL-10, a potent immuno-suppressive cyto-
kine produced especially by lymphocytes and macrop-
hages, and suppression of IL-12.15 Inducible nitric
oxide synthase (iNOS), activated by NF-κB, is another
enzyme that plays pivotal role in mediating, inflamma-
tion, especially as it acts in synergy COX-2.
Curcumin is not only an inexpensive atoxic and
potent COX-2 and iNOS inhibitor,16 it is also a potent
inducer of heat shock proteins (HSPs) and potential
cytoprotector.17,18 Curcumin does not only inhibit
Fig. 1.—Structure of curcumin and its main derivatives.

COX-2, it also inhibits lipooxygenases (LOX) and
leukotreines such as LBT4and 5-hydroxieicosenoic
(5-HETE),19 especially when bound to phosphatidyl-
choline micelles.20 It is also reported to inhibit cytoch-
rome P450 isoenzymes and thereby activation of carci-
nogens.21 Curcumin has the ability to intercept and
neutralize potent prooxidants and carcinogens, both
ROS (superoxide, peroxyl, hydroxyl radicals) and
NOS (nitric oxide —NO—, peroxynitrite).22 It is also a
potent inhibitor of tissue growth factor beta (TGF-β)
and fibrogenesis,23 which is one of the reasons, why it
can be expected to have positive effects in diseases
such as kidney fibrosis, lung fibrosis, liver cirrhosis
and Crohn’s Disease and in prevention of formation of
tissue adhesions.24 Finally, curcumin is suggested to be
especially effective in Th1-mediated immune diseases
as it effectively inhibits Th1 cytokine profile in CD4+T
cells by interleukin-12 production.25
Many medicinal herbs and pharmaceutical drugs are
therapeutic at one dose and toxic at another, and inte-
ractions between herbs and drugs, even if structurally
un-related, may increase or decrease the pharmacologi-
cal and toxicological effects of either component.26,27 It
is suggested that curcumin may increase the bioavaila-
bility of vitamins such as vitamin E and also decrease
cholesterol, as curcumin in experimental studies signi-
ficantly raises the concentration of α-tocopherol in
lung tissues and decreases plasma cholesterol.28
Curcumin in acute and chronic diseases
Atherosclerosis: Oxidation of low density lipopro-
teins (LDL) is suggested to play a pivotal role in the
development of arteriosclerosis, and LDL oxidation
products are toxic to various types of cells including
endothelial cells. Curcumin has a strong capacity to
prevent lipid peroxidation, stabilize cellular membra-
nes, inhibit proliferation of vascular smooth muscle
cells, and inhibit platelet aggregation; all important
ingredients in the pathogenesis of arteriosclerosis. Cur-
cumin was found to be the most effective, when the abi-
lity to inhibit the initiation and propagation phases of
LDL oxidation were compared with a defined antioxi-
dant butylated hydroxy anisole (BHA), capsaisin, quer-
cetin.29 Supply of curcumin, but also capsaicin and garlic
(allecin) to rats fed of a cholesterol-enriched diet preven-
ted both increase in membrane cholesterol and increased
fragility of the erythrocytes.30 Significant prevention of
early atherosclerotic lesions in thoracic and abdominal
aorta are observed in rabbits fed an atherogenic diet for
thirty days, accompanied by significant increases in
plasma concentrations of coenzyme Q, retinol and α-
tocopherol and reductions in LDL conjugated dienes
and in thiobarbituric acid-reactive substances (TBARS),
an expression of ongoing oxidation.31
Cancer: Cancer is a group of more than 100 different
diseases, which manifest itself in uncontrolled cellular
reproduction, tissue invasion and distant metastases.32
Behind the development of these diseases are most
often exposure to carcinogens, which produce genetic
damage and irreversible mutations, if not repaired.
During the last fifty years attempts have been made to
find or produce substances that could prevent these
processes, so called chemopreventive agents. Cancers
are generally less frequent in the developing world,
which has been associated both with less exposure to
environmental carcinogens and to a richer supply of
natural chemopreventive agents. The incidence per
100,000 population is in the USA considerably higher
for the following diseases compared to India: prostatic
cancer (23 X), melanoma skin cancer (male 14 X,
female 9 X), colorectal cancer (male 11 X, female 10
X), endometrial cancer (9 X), lung cancer (male 7 X,
female 17 X), bladder cancer (male 7 X, female 8 X)
breast cancer (5 X), renal cancer (male 9 X, female 12
X).35 These differences are for some diseases such as
breast cancer and prostatic cancer even greater when
compared to China.
The consumption of saturated fat and sugary foods is
much less in the Asian countries, but equally impor-
tant, the consumption of plants with high content of
chemopreventive substances is significantly higher in
these countries. As an example, the consumption of
curcumin has for centuries been about 100 mg/day in
these Asian countries.34 Curcumin induces in vitro
apoptosis of various tumour cell lines: breast cancer
cells,34,35 lung cancer cells,36 human melanoma cells,37
human myeloma cells,38 human leukemia cell lines,39
human neuroblastoma cells,40 oral cancer cells,41 pros-
tatic cancer cells.42-45 Curcumin has, in experimental
models also demonstrated ability to inhibit intrahepatic
metastases.46 Few in vivo experimental studies and no
clinical controlled trials are this far concluded. Howe-
ver, a recent phase I study reported histologic improve-
ment of precancerous lesions in 1 out of 2 patients with
recently resected bladder cancer, 2 out of 7 patients of
oral leucoplakia, 1 out of 6 patients of intestinal meta-
plasia of the stomach, and 2 out of 6 patients with
Bowen’s disease.47 However, the main purpose of the
study was to document that curcumin is not toxic to
humans when taken by mouth for 3 months in a dose of
up to 8 mg/day.
Diabetes: Turmeric (1 g/kg body weight) or curcu-
min (0.08 g/kg body weight) were in a recent study
supplied daily for three weeks to rats with alloxan-
induced diabetes and compared to controls.48 Signifi-
cant improvements were observed in blood glucose,
hemoglobin and glycosylated hemoglobin as well than
in plasma and liver TBARS and glutathione. On the
other hand, it was also observed that the activity of sor-
bitol dehydrogenase (SDH), which catalyzes the con-
version of sorbitol to fructose, was significantly lowe-
red by treatment both with turmeric and curcumin.
Gastric diseases: When the in vitro effects against
19 different Helicobacter pylori strains, including five
cagA+ strains (cag A is the strain-specific H pylori
gene linked to premalignant and malignant lesions)
276 S. Bengmark et al.
Nutr Hosp. 2009;24(3):273-281

were studied, both treatments were found to be equally
effective as both treatments did significantly reduce
growth of all the strains studied.49 Subsequent studies
did also demonstrate that curcumin inhibits infection
and inflammation of gastric mucosal cells through the
inhibition of activation of NF-κB, degradation of
IκBα, NF-κB DNA binding and the activity of IκB
kinases αand β. No curcumin-induced effects were
observed on mitogen-activated protein kinases
(MAPK), extracellular signal regulating kinases 1/2
(ERK1/2) and p38. H pylori-induced mitogenic res-
ponse was completely blocked by curcumin.50 Signifi-
cant antifungal properties against various fungal, espe-
cially phytopathogenic, organisms by curcumin are
also reported.51
Hepatic diseases: Dietary supply of curcuminoids is
also reported to increase hepatic acyl-CoA and prevent
high-fat diet-induced accumulation in the liver and adi-
pose tissues in rats.54 Ethanol-induced steatosis is
known to be further aggravated by supply of polyunsa-
turated fatty acids (PUFA)-rich vegetable oils, which
has been thermally oxidized. Rats gavaged for 45 days
with a diet containing 20% ethanol and 15 % sunflower
oil, heated to 180 oC for 30 min, showed extensive his-
topathological changes with focal and feathery degene-
ration, micronecroses and extensive steatosis in the
liver and extensive inflammation vessel congestion
and fatty infiltration in the kidneys, changes, which lar-
gely could be prevented by simultaneous supply of cur-
cumin or particularly photo-irradiated curcumin, e.g.
curcumin kept in bright sunshine for five hours.53 Both
products were supplied in a dose of 80 mg/kg body
weight. Both products did significantly inhibit eleva-
tions in alkaline phasphatases (ALP) and γ-glutamyl
transferase (γGT). Similar beneficial effects were
observed on histology in various tissues and in hepatic
content of cholesterol, triglycerides free fatty acids and
phospholipids.53 Rats were, in another study for four
weeks, fed with fish oil and ethanol which resulted in
hepatic lesions consisting in fatty liver, necrosis and
inflammation. Supply of curcumin in a daily dose of 75
mg/kg body weight to these rats prevented the histolo-
gical lesions.54 Curcumin was observed to in part to
suppress NF-κB-dependent genes, to block endotoxin-
mediated activation of NF-κB and to suppress the
expression of cytokines, chemokines, COX-2 and
iNOS in Kupffer cells. Similar effects were also obser-
ved in carbon tetrachloride (CCl4)-induced injuries.
Pretreatment during four days with curcumin (100
mg/kg body weight) before intraperitoneal injection of
CCl4prevented significantly subsequent increases in
TBARS, alanine aminotransferase (ALT) and aspertate
aminotransferase (AST) and in hydroxyproline (μg/g
liver tissue).55 A recent study has shown that curcumin
administration prevent the reduction of cytochrome
enzyme P450 expression induced in inflammatory
situations.56
Pancreatic diseases: The effect of curcumin to
reduce the damage to pancreas was studied in two dif-
ferent models; cerulein-induced and ethanol and cole-
cistokinin (CCK)-induced pancreatitis.57 Curcumin
was administered intravenously in parallel with induc-
tion of pancreatitis; a total of 200 mg/kg body weight
was administered during the treatment period of six
hours. Curcumin treatment reduced significantly histo-
logical injuries, the acinar cell vacuolization and neu-
trophil infiltration of the pancreatic tissue, the intra-
pancreatic activation of trypsin, the hyperamylasemia
and hyperlipasemia, and the pancreatic activation of
NF-κB, IκB degradation, activation of activator pro-
tein (AP)-1and various inflammatory molecules such
as IL-6, TNF-α, chemokine KC, iNOS and acidic ribo-
somal phosphoprotein (ARP). Curcumin did in both
models also significantly stimulate pancreatic activa-
tion of caspase-3.57
Intestinal diseases: Pretreatment during 10 days with
curcumin in a daily dose of 50 mg/kg body weight
before induction of trinitrobenzene sulphonic acid
(TNBS) colitis resulted in a significant reduction in
degree of histological tissue injury, neutrophil infiltra-
tion (measured as decrease in myeloperoxidase activity)
and lipid peroxidation (measured as decrease in malon-
dialdehyde activity) in the inflamed colon, as well as in a
decreased serine protease activity.58 A significant reduc-
tion in NF-κB activation and reduced levels of NO,
superoxide anion and a regulation of the immune func-
tion were also found. Specifically, a marked suppression
of Th1 functions, through a lower expression of interfe-
ron gamma (IFNγ) mRNA and a better Th2 protective
expression improved colonic mucosa induced damage.58
In another similarly designed study curcumin was added
to the diet during 24 h before and 2 wk after the induction
of TNBS colitis. A significant reduction in COX-2 and
iNOS expression could be attributed to the lower activa-
tion of MAPK p38.59 Indeed, curcumin modulates proin-
flammatory cytokines expression, attenuating IL-1β
TNBS-induced damage, and increase IL-10 expres-
sion.60 Curcumin was also supplied in combination with
caffeic acid phenethyl ester to animals treated with
cytostatic drugs (arabinose cytosine and methotrexate).
The treatment did not only inhibit the NF-κB induced
mucosal barrier injury but was also shown to increase
the in vitro susceptibility of the non-transformed small
intestinal rat epithelial cell to the cytostatic agents.61
However, a recent study has shown that the effect of cur-
cumin of TNBS-induced damage on intestinal mucosa
depend on the experimental model. These authors con-
cluded that the therapeutic value of curcumin depends
on the nature of the immune alteration during intestinal
bowel disease.62
Neurodegenerative diseases: A growing body of
evidence implicates free radical toxicity, radical indu-
ced mutations and oxidative enzyme impairment and
mitochondrial dysfunction in neurodegenerative disea-
ses (NDD). Significant oxidative damage is observed
in all NDD, which in the case of Alzheimer disease
(AD) leads to extracellular deposition of β-amyloid
(Aβ) as senile plaques.
Turmeric and curcuminoids 277Nutr Hosp. 2009;24(3):273-281

Nonsteroidal anti-inflammatory drugs (NSAIDs)
like ibuprofen has proven effective to prevent progress
of AD in animal models,63 but gastrointestinal and
occasional liver and kidney toxicity induced by inhibi-
tion of COX-1 precludes widespread chronic use of the
drug.64 Use of antioxidants such as vitamin E (α-tocop-
herol) has proven rather unsuccessful even when high
doses were used.65 Vitamin E, α-tocopherol, is in con-
trast to γ-tocopherol a poor scavenger of NO-based free
radicals. However, Curcumin is a several times more
potent scavenger than vitamin E,66 and in addition also a
specific scavenger of NO-based radicals.67 When tried
in a transgenic mouse model of AD a modest dose (24
mg/kg body weight), but not a > 30 times higher dose
(750 mg/kg body weight) of curcumin did significantly
reduce oxidative damage and amyloid pathology.68
Similar observations, reductions in both Aβdeposits
and in memory deficits are also made in Sprague Daw-
ley rats.69 The age-adjusted prevalence of both AD70
and Parkinson’s disease71 is in India, with its signifi-
cantly higher intake of turmeric, much lower than in
Western countries, especially the USA. However, the
preventive effects of consumption of turmeric can also
be achieved with other polyphenol-rich fruits and
vegetables if consumed in enough quantities. Bluebe-
rries, strawberries and spinach in doses of 18.6, 14.8
and 9.1 g of dried extract/kg body weight were
demonstrated effective in reversing age-related deficits
in both neuronal and behavioural parameters.72 A study
from 1999 is of special interest. Rats on chronic etha-
nol supply were randomized to 80 mg/kg body weight
of curcumin or control and compared to non-intoxica-
ted normal rats.73 The degree of histopathological chan-
ges and levels of TBARS, cholesterol, phospholipids,
and free fatty acids in brain tissue were significantly
improved after curcumin treatment.
Ocular diseases: Cataract, an opacity of the eye lens,
is the leading cause of blindness worldwide, responsible
for blindness of almost 20 million in the world.74 Nutri-
tional deficiencies, especially lack of consumption of
enough antioxidants, diabetes, excessive sunlight, smo-
king and other environmental factors are known to incre-
ase the risk of cataracts.75 However, the age-adjusted
prevalence of cataract in India is, however, three times
that of the United States,76 despite that have three diffe-
rent experimental studies reported significant preventive
effects of curcumin against cataracts induced by napht-
halene,77 galactose,78 and selenium.79
Respiratory diseases: As mentioned above, curcu-
min is a potent inhibitor of TGF-αand fibrogenesis,24
and suggested to have positive effects in fibrotic disea-
ses in kidneys, liver, intestine (Crohn’s Disease), body
cavities (prevention of fibrous adhesions)18 and on con-
ditions with lung fibrosis,80 including cystic fibrosis.
The latter is of special interest as it has been especially
linked to glutathione deficiency. The effect of curcu-
min against amiodarone-induced lung fibrosis was
recently studied in rats.80 Significant inhibition of lac-
tate dehydrogenase (LDH) activity, infiltration of neu-
trophils, eosinophils and macrophages in lung tissue,
lipopolysaccharide (LPS)-stimulated TNF-αrelease,
phorbole myristate acetate (PMA)-stimulated supero-
xide generation, myeloperoxidase (MPO) activity,
TGF-β1 activity, lung hydroxyproline content and
expression of type I collagen and c-Jun protein were
observed when curcumin was supplemented in a dosis
of 200 mg/kg body weight in parallel with intratracheal
instillation of 6.25 mg/kg body weight of amiodarone.80
Curcumin exhibits structural similarities to isoflavo-
noid compounds that seem to bind directly to the CFTR
protein and alter its channel properties.79 Egan et al,80
who had previously observed that curcumin inhibits a
calcium pump in endoplasmic reticulum, thought that
reducing the calcium levels might liberate the mutant
Cystic fibrosis transmembrane conductance regulator
(CFTR) and increase its odds of reaching the cell sur-
face- see also.81 Previously, Egan et al observed that
curcumin inhibits endoplasmic reticulum calcium
bomb and proposed that calcium reduction may release
a mutated CFTR that is able to reach cell surface.82 The
ΔF508 mutation, the most common cause of cystic
fibrosis, will induce a misprocess in the endoplasmatic
reticulum of a mutant CFTR gene. A dramatic increase
in survival rate and in normal cAMP-mediated chloride
transport across nasal and gastrointestinal epithelia
was observed in gene-targeted mice homozygous for
the ΔF508 when supplemented curcumin.83 No human
studies are yet reported and it is too early to know if
this treatment will be able to halt or reverse the
decline in lung function also in patients with cystic
fibrosis. An eventual anti-asthmatic effect of curcumin
was recently tested in guinea-pigs sensitized with oval-
bumin and significant reductions observed both in air-
way constriction and in airway hyperreactivity to hista-
mine.84
Tobacco/cigarette smoke-induced injuries: Ciga-
rette smoke is suggested to cause 20% of all deaths and
~30% of all deaths from cancer. This smoke contains
thousands of compounds of which about hundred are
known carcinogens, co-carcinogens, mutagens and/or
tumor promoters. Each puff of smoke contains over 10
trillion free radicals. Antioxidant levels in blood are
also significantly reduced in smokers. Activation of
NF-κB has been implicated in chemical carcinogenesis
and tumorigenesis through activation of several genes
such as COX-2, iNOS, MMP-9, IL-8, cell surface
adhesion molecules, anti-apoptotic protein and others.
A recent study reports that curcumin abrogates the acti-
vation of NF-κB, which correlates with down-regula-
tion of COX-2, MMP-9 and cyclin D1 in human lung
epithelial cells.85
Plant antioxidants - released by gastrointestinal
microbiota
All chronic diseases are in a way related, they deve-
lop all as a result of a prolonged and exaggerated
278 S. Bengmark et al.
Nutr Hosp. 2009;24(3):273-281

inflammation.86 Their development can most likely be
prevented or at least delayed by extensive consumption
of antioxidants such as curcumin. It is important to
remember, that it is almost exclusively through micro-
bial fermentation of the different plants that bioactive
antioxidants are released and absorbed. Clearly flora
and supplied lactic acid bacteria/probiotics play an
important role. It is therefore unfortunate that both size
and diversity of flora is impaired and intake of probio-
tic bacteria significantly reduced among Westerners.
For example, reduction in total numbers and diversity
of flora is also associated with certain chronic diseases
such as inflammatory bowel disease.87 A study from
1983 demonstrated that Lb. plantarum, a strong fibre
fermentor, is found in only 25 % of omnivorous Ameri-
cans and in about 2/3 of vegetarian Americans.88 Great
differences in volume and diversity of flora have also
been observed between different human cultures. It is
reported that Scandinavian children have compared to
Parkistani children a much reduced flora.89
Astronauts, who return from space flights have during
the flight lost most of their commensal flora including
lactobacillus species such as Lb. plantarum (lost to
almost 100%), Lb. casei (lost to almost 100%), Lb. fer-
mentum (reduced by 43%), Lb. acidophilus (reduced by
27%), Lb. salivarius (reduced by 22%) and Lb. brevis
(reduced by 12%),90 changes most likely attributed to
poor eating (dried food, no fresh fruits and vegetables)
and a much reduced intake of plant fibers and natural
antioxidants, to the mental and physical stress and even-
tually also to the lack of physical exercise. Many indivi-
duals in Western Societies exhibit a type of “astronaut-
like lifestyle” with unsatisfactory consumption of fresh
fruits, vegetables, too much stress and no or little out-
door/sport activities. Furthermore, flora seems not to
tolerate exposure to chemicals including pharmaceuti-
cals. This is also demonstrated in critically ill, who most
often have lost their entire lactobacillus flora.91 A recent
Scandinavian study suggest that fiber-fermenting lacto-
bacilli such as Lb. plantarum, Lb. rhamnosus and Lb.
paracasei ssp paracasei, present in all humans with a
rural lifestyle, are only found 52%, 26% and 17% res-
pectively of persons with a more urban Western type
lifestyle.92 These lactobacilli are present in all with more
rural lifestyle. The lack of these lactobacilli is probably
negative as these lactobacilli are unique in their ability to
ferment important fibers such as inulin and phlein, other-
wise resistant to fermentation by most lactobacillus spe-
cies,93 and superior to other lactobacillus in their ability
to eliminate pathogenic microorganisms such as Clostri-
dium difficile.94 Thus, the lower presence of intestinal
bacteria may influence the production of bioactive antio-
xidants from vegetables.
Conclusive remarks
To use medicinal plants and their active components
is becoming an increasingly attractive approach for the
treatment of various inflammatory disorders among
patients unresponsive or unwilling to take standard
medicines. Food derivates have the advantage of being
relatively non-toxic. Within them, curcuminoids, such
as curcumin, are chemopreventive agents from turme-
ric curry foods. Its bioavailability on oral supplementa-
tion is low but also its toxicity. Several studies has
demonstrated a number of beneficial properties on
inflammatory chronic diseases such as atherosclerosis,
cancer, diabetes, gastric, hepatic, pancreatic, intestinal
neurodegenerative, ocular and respiratory diseases as
well as on tobacco smoke-induced injuries.
Mechanisms of action are related to its antioxidant
activity, able to neutralise oxygen and nitrogen reac-
tive species, antiinflamatory properties, by decreasing
activation of NF-κB and inhibiting COS-2, iNOS,
LOX, LT, cytochrome P450 isoenzymes, TGF-βand
fibrogenesis, and also to its immunosuppressive capa-
city, able to modulate cytokine and chemokine produc-
tion. On the other hand, curcumin is able to prevent
carcinogen activation.
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