ArticlePDF AvailableLiterature Review

Abstract

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies.
molecules
Review
Curcumin and Health
Mario Pulido-Moran 1, 2, , Jorge Moreno-Fernandez 2 ,3 ,, Cesar Ramirez-Tortosa 4
and MCarmen Ramirez-Tortosa 1, 2, *
1Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia,
Campus Universitario de Cartuja, Universidad de Granada, 18071 Granada, Spain; mpulido@ugr.es
2Instituto de Nutrición y Tecnología de los Alimentos José Mataix Verdú, Centro de Investigaciones
Biomédicas, Avenida del Conocimiento s/n, Campus Tecnológico y Ciencias de la Salud,
Universidad de Granada, Armilla (Granada) 18016, Spain
3Departamento de Fisiología, Facultad de Farmacia, Campus Universitario de Cartuja,
Universidad de Granada, 18071 Granada, Spain; jorgemf@correo.ugr.es
4Servicio de Anatomía Patológica, Complejo Hospitalario de Jaen, 23007 Jaén, Spain;
cesarl.ramirez.sspa@juntadeandalucia.es
*Correspondence: mramirez@ugr.es; Tel.: +34-628-489-683
These authors contributed equally to this work.
Academic Editors: Maurizio Battino, Etsuo Niki and José L. Quiles
Received: 15 December 2015 ; Accepted: 22 February 2016 ; Published: 25 February 2016
Abstract:
Nowadays, there are some molecules that have shown over the years a high capacity
to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or
cancer. This article provides a brief review about the origin, bioavailability and new research on
curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects
such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory
properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin
is positioned as an interesting nutraceutical. This is the reason why it has been subjected to
several modifications in its structure and administration form that have permitted an increase
in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity
associated to these pathologies.
Keywords:
curcumin; bioavailability; antioxidant; ROS; anti-inflammatory; cancer; lung diseases;
liver disorders; cardiovascular diseases; natural compound
1. Introduction
Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] also called
diferuloylmethane, is the main natural polyphenol found in the rhizome of Curcuma longa
(turmeric) and in others Curcuma spp. [
1
]. Curcuma longa has been traditionally used in Asian
countries as a medical herb for several pathologies due to its antioxidant, anti-inflammatory [
2
],
antimutagenic, antimicrobial [3,4], and anticancer properties [5,6].
In relation to the solubility properties, curcumin is soluble in alkali or in extremely acidic
solvents [
7
]. It is a crystalline compound with a bright orange-yellow colour so it is used as food
colorant [
2
]. It is a keto-enol tautomeric compound with a predominant keto-form in acid or neutral
solutions and the enol-form is predominant in alkalis solutions with good properties as chelator of
metal ions [
8
]. Different activities have been directly associated according to the keto or enol forms of
curcumin [9].
In the last 50 years it has been proven that most of the effects of Curcuma longa are
mainly due to curcumin, with a potential effects against diabetes, allergies, arthritis, Alzheimer’s
Molecules 2016,21, 264; doi:10.3390/molecules21030264 www.mdpi.com/journal/molecules
Molecules 2016,21, 264 2 of 22
disease [
10
,
11
], and other chronic illnesses [
9
,
12
]. However, besides curcumin, there are others
components in Curcuma longa called the curcuminoids group. They are demethoxycurcumin and
bis-demethoxycurcumin. Curcumin is the most abundant of the curcuminoids group (77% of the total
weight) [
13
] and this group constitutes around 5% of the total component of Curcuma longa. According
to their structures (Figure 1), some researchers have concluded that the methoxy groups on the phenyl
rings in curcumin are important to have health effects [
14
]. Moreover, it has been described that these
curcuminoids have synergistic action for example to have nematocidal activity [
15
]. The aim of this
review is to improve the knowledge of curcumin’s effects on health and try to elucidate its different
mechanisms of action against different pathologies.
Molecules 2016, 21, 264 2 of 21
longa called the curcuminoids group. They are demethoxycurcumin and bis-demethoxycurcumin.
Curcumin is the most abundant of the curcuminoids group (77% of the total weight) [13] and this
group constitutes around 5% of the total component of Curcuma longa. According to their structures
(Figure 1), some researchers have concluded that the methoxy groups on the phenyl rings in curcumin
are important to have health effects [14]. Moreover, it has been described that these curcuminoids
have synergistic action for example to have nematocidal activity [15]. The aim of this review is to
improve the knowledge of curcumin’s effects on health and try to elucidate its different mechanisms
of action against different pathologies.
Figure 1. Chemical structures of curcuminoids (methoxy groups in curcumin are shown by
discontinuous lines).
2. Bioavailability and Metabolism of Curcumin
In the last ten years, many studies with animals and in vitro models have been performed with
the objective of stablishing the mechanisms of action of curcumin and its activities against several
pathologies [16]. For this reason, there are many studies that aim to understand the bioavailability of
curcumin. The first study performed to determine the biological availability was carried out by
Wahlstrom and Blennow in 1978, where curcumin was administered to Sprague-Dawley rats at a
1 g/kg dose. In this study a low level of curcumin was observed in blood plasma of rats [17]. However,
latter studies demonstrated that when curcumin was administered orally at a dose of 2000 mg/kg
to rats, the maximum serum concentration was 1.35 ± 0.23 µg/mL although in humans it was
undetectable [18].
Some studies with rats have shown that the oral bioavailability of curcumin was around 1% [19]
so very high doses of curcumin are necessary (3600 to 12,000 milligrams) to achieve any beneficial
effects. Sharman et al., described no toxic effect of curcuma administered orally in patients with
colorectal cancer [20]. This latter study showed that curcumin metabolites were detected in plasma
when patients ingested at least 3600 milligrams of curcumin being mainly detected as curcumin
glucuronide and curcumin sulphate. In urine samples, curcumin and its metabolites were detected
primarily as curcumin, followed by glucuronide and finally as sulphate forms.
If curcumin is administered to rats in a dose of 2000 mg/kg jointly with L-piperoylpiperidine that
induces glucuronyl transferase enzymes, the bioavailability of curcumin increases around 154% [18].
To determine the pharmacokinetic and pharmacodynamic properties of curcumin some
researchers have measured the radioactivity after administration of [3H]-curcumin to rats, showing
the great difficulty of curcumin in the intestinal absorption process [21–23]. In addition, these
studies showed that curcumin suffers a biotransformation during the absorption from the bowel to
glucuronides of tetrahydrocurcumin and hexahydrocurcumin derivatives. A further study was
performed in liver to determine the nature of curcumin metabolites. These studies suggested that
curcumin is firstly transformed to dihydrocurcumin and tetrahydrocurcumin by reductases and
they are then transformed into monoglucuronide conjugates as dihydrocurcumin-glucuronide and
Figure 1.
Chemical structures of curcuminoids (methoxy groups in curcumin are shown by
discontinuous lines).
2. Bioavailability and Metabolism of Curcumin
In the last ten years, many studies with animals and
in vitro
models have been performed with
the objective of stablishing the mechanisms of action of curcumin and its activities against several
pathologies [
16
]. For this reason, there are many studies that aim to understand the bioavailability
of curcumin. The first study performed to determine the biological availability was carried out by
Wahlstrom and Blennow in 1978, where curcumin was administered to Sprague-Dawley rats at a 1 g/kg
dose. In this study a low level of curcumin was observed in blood plasma of rats [
17
]. However, latter
studies demonstrated that when curcumin was administered orally at a dose of 2000 mg/kg to rats, the
maximum serum concentration was 1.35
˘
0.23
µ
g/mL although in humans it was undetectable [
18
].
Some studies with rats have shown that the oral bioavailability of curcumin was around 1% [
19
]
so very high doses of curcumin are necessary (3600 to 12,000 milligrams) to achieve any beneficial
effects. Sharman et al., described no toxic effect of curcuma administered orally in patients with
colorectal cancer [
20
]. This latter study showed that curcumin metabolites were detected in plasma
when patients ingested at least 3600 milligrams of curcumin being mainly detected as curcumin
glucuronide and curcumin sulphate. In urine samples, curcumin and its metabolites were detected
primarily as curcumin, followed by glucuronide and finally as sulphate forms.
If curcumin is administered to rats in a dose of 2000 mg/kg jointly with L-piperoylpiperidine that
induces glucuronyl transferase enzymes, the bioavailability of curcumin increases around 154% [18].
To determine the pharmacokinetic and pharmacodynamic properties of curcumin some
researchers have measured the radioactivity after administration of [3H]-curcumin to rats, showing
the great difficulty of curcumin in the intestinal absorption process [
21
23
]. In addition, these
studies showed that curcumin suffers a biotransformation during the absorption from the bowel
to glucuronides of tetrahydrocurcumin and hexahydrocurcumin derivatives. A further study was
performed in liver to determine the nature of curcumin metabolites. These studies suggested that
curcumin is firstly transformed to dihydrocurcumin and tetrahydrocurcumin by reductases and
they are then transformed into monoglucuronide conjugates as dihydrocurcumin-glucuronide and
tetrahydrocurcumin-glucuronide by
β
-glucuronidase [
24
]. The transformations that curcumin suffers
Molecules 2016,21, 264 3 of 22
are shown in Figure 2. The transformation in gut and liver can lead to generate curcumin glucuronides
and curcumin sulphates or, alternately, reduced molecules like hexahydrocurcumin [25].
Molecules 2016, 21, 264 3 of 21
tetrahydrocurcumin-glucuronide by β-glucuronidase [24]. The transformations that curcumin suffers
are shown in Figure 2. The transformation in gut and liver can lead to generate curcumin glucuronides
and curcumin sulphates or, alternately, reduced molecules like hexahydrocurcumin [25].
Figure 2. Metabolite derivatives of curcumin.
On the other hand, Ryu et al. [26] demonstrated that curcumin administered intravenously in
mice as [18F]-curcumin was accumulated in the liver, spleen, lung and in brain. These authors
concluded that curcumin has a specific affinity for some tissues.
Finally, the excretion of curcumin metabolites depends on the vehicle and the route of
administration employed [27]. For oral administration, a 75% of curcumin metabolites were found
only in faeces but not in urine [17]. However, when the curcumin was administrated intraperitoneally
73% of these metabolites were found in faeces and around 11% in urine [28]. In relation with the
administration form, encapsulation in liposomes, polymeric nanoparticles, cyclodextrin encapsulation,
lipid complexes or by synthesis of polymer-curcumin complex have been investigated. All of them
have helped increase the activity and bioavailability [29] of this compound and to improve the
beneficial effect of curcumin against some pathologies such as cancer [30,31] or liver diseases [32].
3. Role of Curcumin in Health
It is known that some diseases are produced by an unhealthy diet (i.e., cardiovascular diseases)
and as Wood and Brooks suggest, “We are what we ate” [33]. In this sense, they are evidences that
certain diets rich in antioxidants, as the Mediterranean, Indian or Nepalese diets, are excellent against
some pathologies related with oxidative stress as cardiovascular diseases [34,35], cancer [36],
metabolic disorders [37] or aging, improving the mortality and morbidity of them [38]. Particularly,
many of the effects associated to Indian or Nepalese diets have been related with specific compounds
such as curcumin and other curcuminoids [39].
3.1. Antioxidant Activity and ROS Scavenger Properties
Curcumin is considered as antioxidant due to the β-diketone group in its structure [14,40,41].
Joe and Lokesh determined in 1994 that the most important mechanisms by which curcumin is able
to promote the majority of its activities are by inhibition of superoxide radicals, hydrogen peroxide
and nitric oxide radical [42]. Other studies proposed that curcumin also enhances the activity of many
antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) [43]
and heme oxygenase-1 (OH-1) [44]. These activities reduce the lipid peroxidation decreasing the
Figure 2. Metabolite derivatives of curcumin.
On the other hand, Ryu et al. [
26
] demonstrated that curcumin administered intravenously in mice
as [18F]-curcumin was accumulated in the liver, spleen, lung and in brain. These authors concluded
that curcumin has a specific affinity for some tissues.
Finally, the excretion of curcumin metabolites depends on the vehicle and the route of
administration employed [
27
]. For oral administration, a 75% of curcumin metabolites were found
only in faeces but not in urine [
17
]. However, when the curcumin was administrated intraperitoneally
73% of these metabolites were found in faeces and around 11% in urine [
28
]. In relation with the
administration form, encapsulation in liposomes, polymeric nanoparticles, cyclodextrin encapsulation,
lipid complexes or by synthesis of polymer-curcumin complex have been investigated. All of them have
helped increase the activity and bioavailability [
29
] of this compound and to improve the beneficial
effect of curcumin against some pathologies such as cancer [30,31] or liver diseases [32].
3. Role of Curcumin in Health
It is known that some diseases are produced by an unhealthy diet (i.e., cardiovascular diseases)
and as Wood and Brooks suggest, “We are what we ate” [
33
]. In this sense, they are evidences that
certain diets rich in antioxidants, as the Mediterranean, Indian or Nepalese diets, are excellent against
some pathologies related with oxidative stress as cardiovascular diseases [
34
,
35
], cancer [
36
], metabolic
disorders [
37
] or aging, improving the mortality and morbidity of them [
38
]. Particularly, many of
the effects associated to Indian or Nepalese diets have been related with specific compounds such as
curcumin and other curcuminoids [39].
3.1. Antioxidant Activity and ROS Scavenger Properties
Curcumin is considered as antioxidant due to the
β
-diketone group in its structure [
14
,
40
,
41
].
Joe and Lokesh determined in 1994 that the most important mechanisms by which curcumin is able
to promote the majority of its activities are by inhibition of superoxide radicals, hydrogen peroxide
and nitric oxide radical [
42
]. Other studies proposed that curcumin also enhances the activity of
many antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase
(GPx) [
43
] and heme oxygenase-1 (OH-1) [
44
]. These activities reduce the lipid peroxidation decreasing
the hepatic damage [
45
,
46
]. In addition, curcumin is also able to increase the activity of xenobiotic
detoxifying enzymes both in liver and kidneys, protecting against carcinogenesis processes [47].
Molecules 2016,21, 264 4 of 22
Other studies have described that a dose of 200 mg/kg of curcumin increased the SOD and
catalase activities and the hepatic total antioxidant capacity in liver from rats with hepatic damage and
high level of oxidative stress provoked by thallium acetate [48].
In human hepatocyte L02 cell line curcumin was able to avoid the ROS formation by increasing
SOD activity and reducing glutathione levels after treatment with the antimicrobial feed additive
quinocetone as a generator of free radicals [49].
In addition, curcumin can upregulate other enzymes like glutathione transferase and their mRNAs
as well as increase both the level of reduced glutathione and the acid-soluble sulphydryl groups [
50
]
and scavenge free radicals [
51
]. All these effects together have granted it a health- and radioprotective
role [
42
,
45
,
52
54
]. Moreover, curcumin can increase the levels of reduced gluthathione (GSH) and it
can moderate the malondialdehyde levels in a lung carcinogenesis model induced by benzo(a)pyrene
(a major carcinogenic pollutant) in mice [
55
]. The main antioxidant activities and ROS scavenger
properties of curcumin in the biological system are described in Figure 3.
Molecules 2016, 21, 264 4 of 21
hepatic damage [45,46]. In addition, curcumin is also able to increase the activity of xenobiotic
detoxifying enzymes both in liver and kidneys, protecting against carcinogenesis processes [47].
Other studies have described that a dose of 200 mg/kg of curcumin increased the SOD and
catalase activities and the hepatic total antioxidant capacity in liver from rats with hepatic damage
and high level of oxidative stress provoked by thallium acetate [48].
In human hepatocyte L02 cell line curcumin was able to avoid the ROS formation by increasing
SOD activity and reducing glutathione levels after treatment with the antimicrobial feed additive
quinocetone as a generator of free radicals [49].
In addition, curcumin can upregulate other enzymes like glutathione transferase and their mRNAs
as well as increase both the level of reduced glutathione and the acid-soluble sulphydryl groups [50]
and scavenge free radicals [51]. All these effects together have granted it a health- and radioprotective
role [42,45,52–54]. Moreover, curcumin can increase the levels of reduced gluthathione (GSH) and it
can moderate the malondialdehyde levels in a lung carcinogenesis model induced by benzo(a)pyrene
(a major carcinogenic pollutant) in mice [55]. The main antioxidant activities and ROS scavenger
properties of curcumin in the biological system are described in Figure 3.
Figure 3. This figure shows a brief summary of the antioxidant properties and ROS scavenger effects
of curcumin. (A) Effect of curcumin as ROS and RNS scavengers; (B) Enhanced activities of curcumin
on different antioxidant systems.
Some studies have determined that curcumin is able to prevent the brain injury thanks to the
suppression of oxidative stress via Akt/Nrf2 (Nuclear factor-E2-related factor 2) pathway, acting then
as neuroprotector [56]. Li et al. [57] proved the neuroprotector effect of curcumin by decreasing the
reactive oxygen species (ROS)-associated endoplasmic reticulum (ER) stress (related to neuronal
damage) through the regulation of AMPK activity. Similar results were obtained by Fu, Yang et al.
[58] who tried to determine if curcumin could protect PC12 cells from H
2
O
2
-induced neurotoxicity,
These authors described that curcumin dysregulated the mitogen-activated protein kinase (MAPK)
and AKT pathways, decreasing apoptotic cells through inhibition of ROS accumulation [58].
Curcumin expresses a dichotomy between its antioxidant and pro-oxidant effects, generally
depending on the dose used and the presence in the medium of metal ions [50,59,60]. Curcumin can
selectively provoke the induction of pro-oxidant effects only in malignant cells for example in cervical
cancer cells [61], cell lung cancer NCI-H446 [62] or in murine myelomonocytic leukemia WEHI-3 cells
[63]. These studies described that curcumin promotes a powerful increase in the intracellular generation
of ROS or ER-stress by provoking a mitochondrial dysfunction.
Figure 3.
This figure shows a brief summary of the antioxidant properties and ROS scavenger effects
of curcumin. (
A
) Effect of curcumin as ROS and RNS scavengers; (
B
) Enhanced activities of curcumin
on different antioxidant systems.
Some studies have determined that curcumin is able to prevent the brain injury thanks to the
suppression of oxidative stress via Akt/Nrf2 (Nuclear factor-E2-related factor 2) pathway, acting
then as neuroprotector [
56
]. Li et al. [
57
] proved the neuroprotector effect of curcumin by decreasing
the reactive oxygen species (ROS)-associated endoplasmic reticulum (ER) stress (related to neuronal
damage) through the regulation of AMPK activity. Similar results were obtained by Fu, Yang et al. [
58
]
who tried to determine if curcumin could protect PC12 cells from H
2
O
2
-induced neurotoxicity, These
authors described that curcumin dysregulated the mitogen-activated protein kinase (MAPK) and AKT
pathways, decreasing apoptotic cells through inhibition of ROS accumulation [58].
Curcumin expresses a dichotomy between its antioxidant and pro-oxidant effects, generally
depending on the dose used and the presence in the medium of metal ions [
50
,
59
,
60
]. Curcumin can
selectively provoke the induction of pro-oxidant effects only in malignant cells for example in cervical
cancer cells [
61
], cell lung cancer NCI-H446 [
62
] or in murine myelomonocytic leukemia WEHI-3
cells [
63
]. These studies described that curcumin promotes a powerful increase in the intracellular
generation of ROS or ER-stress by provoking a mitochondrial dysfunction.
3.2. Curcumin and Inflammation
The inflammatory cascade plays an important role in the development of chronic illnesses such as
autoimmune, cardiovascular, endocrine, neurodegenerative and neoplastic diseases [
64
66
]. Curcumin
is able to decrease inflammation by interacting with many inflammatory processes [6770].
Molecules 2016,21, 264 5 of 22
Oxidative stress can lead to chronic inflammation, causing chronic diseases [
71
]. ROS production
modulates the expression of thebnuclear factor-
κβ
(NF-
κβ
) and tumour necrosis factor alpha (TNF-
α
)
pathways which play a central role in the inflammatory response [
72
]. Curcumin could downregulate
oxidative stress and the subsequent inflammation through the Nrf2 pathway. This polyphenol
can decrease TNF
α
production and the cell signalling mediated by TNF
α
in various types of
cells.
In vitro
and
in vivo
studies postulate that curcumin is a TNF
α
blocker due to its direct
union to TNF
α
[
73
,
74
]. In this sense, curcumin modulates TNF-
α
expression by inhibition of
p300/CREB-specific acetyltransferase which leads to repression of acetylation of histone/nonhistone
proteins and therefore repression of transcription [
74
]. Regarding NF-
κβ
the primary transcription
factor involved in the start of the inflammatory processes, can be blocked by curcumin [
75
].
This molecule inhibits the IkBkinase provoking a NF-κβ inhibition.
Curcumin also inhibits inflammatory cytokines, such as interleukins (ILs), chemokines, as well as
inflammatory enzymes, such as cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and
others molecules as cyclinD1 [
76
]. This natural anti-inflammatory agent is able to inhibit MAPK and
NF-
κ
B pathways in TNF-
α
-treated HaCaT cells and, therefore, IL-1
β
and IL-6 expression [
77
]. In others
studies in BV2 microglia cell stimulated with lipopolysaccharide (LPS), curcumin also inhibited IL6
and TNF-
α
[
78
]. Due to all its anti-inflammatory properties, curcumin is able to improve different
chronic diseases as follows.
3.2.1. Inflammation of Respiratory System
Allergy is a pro-inflammatory disease mediated by cytokines [
79
]. In asthma development, others
inflammatory molecules such as eotaxin, monocyte chemoattractant protein-1 (MCP-1) and MCP-3
play also an important role. In this sense, in 2015 Panahi et al., studied the anti-inflammatory properties
of curcuminoides in sulphur mustard-intoxicated subjects. These authors found a great effect of
curcuminoides vs. placebo in modulating all assessed inflammatory mediators included MCP-1 [80].
There are many studies which confirm the important role of curcumin in respiratory diseases
caused by inflammation [
81
]. In acute allergic asthma in BALB/c mice, the anti-inflammatory effect of
curcumin, the down-regulated levels of Notch1/2 receptors and globin transcription factor 3 (GATA3)
was reported [
82
]. Studies of plants extracts with anti-asthmatic components showed that curcumin can
act as a scavenger of nitric oxide and could prevent bronchial inflammation in asthmatic patients [
83
].
Moreover, curcumin can also decrease allergic inflammation in asthma models by regulating Treg/Th17
balance with an important increase of Treg cells [84].
3.2.2. Inflammation of Joints
ROS play a crucial role in joint destruction in rheumatoid arthritis [
85
,
86
]. These free radicals
can activate many transcription factors such as NF-
κβ
and activator protein 1 (AP-1), which regulate
growth factors, chemokines, inflammatory cytokines and anti-inflammatory molecules [
87
]. Curcumin
as an anti-inflammatory and antioxidant compound possesses anti-rheumatic and anti-arthritic
properties [
88
,
89
]. In patients with rheumatoid arthritis, curcumin is able to up regulate pro-apoptotic
Bax, and down regulate anti-apoptotic B-cell lymphoma 2 (Bcl-2) and X-linked inhibitor of apoptosis
protein (XIAP), inducing apoptosis and, therefore, inhibit the growth of synovial fibroblasts [
90
].
Curcumin also prevents the antiinflammatory response in synovial fibroblasts by inhibition of
prostaglandin E2 (PGE2) synthesis due to COX-2 suppression [91].
3.2.3. Digestive System Inflammation
Inflammatory bowel disease is characterized by oxidative stress, nitrosative stress, leukocyte
infiltration and production of pro-inflammatory cytokines. NF-
κβ
also takes part in this disease
producing cytokines and chemokines for inflammation [
92
]. Curcumin is able to suppress STAT3
pathways, reducing the expression of TNF
α
, and IL-1
β
. Moreover, this molecule can improve dextran
sulphate sodium (DSS)-induced colitis because it decreases myeloperoxidase activity, colon injury,
Molecules 2016,21, 264 6 of 22
oxidative stress, inflammatory reaction, and apoptotic cell death by blocking c-Jun N-terminal protein
kinase (JNK), p38 MAPK pathways [
93
,
94
]. According to this, other studies showed that curcumin
blocked p38 MAPK and Akt pathways, decreased NF-
κβ
level and inhibited the expression of vascular
cell adhesion molecule 1 (VCAM-1) in human intestinal microvascular endothelial cells (HIMECs) and
in 2,4,6-trinitrobenzenesulphonic acid-induced colitis in mice [9597].
In others digestive diseases such as chronic pancreatitis many factors can participate (alcohol
tobacco, genetic, environmental, hypertriglyceridemia, hypercalcemia, autoimmune) [
98
]. Curcumin
reduces inflammation by decreasing NF-
κβ
, AP-1, iNOS, TNF-
α
, and IL-6 molecules in rats with
pancreatitis [
99
]. In pancreatitis induced by ethanol and cerulein, curcumin improves disease’s severity,
acting on serum amylase, pancreatic trypsin, and neutrophil infiltration [
100
].
Dhillon et al.
, [
101
]
described that curcumin has biological activity in patients with pancreatic cancer. Curcumin
down-regulated expression of NF-κβ and COX-2.
Some studies evaluated the effect of curcumin in gastric mucosa inflammation provoked
by Helicobacter pylori. In these studies, curcumin decreased the levels of inflammatory cytokines,
chemokines, the expression of toll-like receptors (TLRs) and myeloid differentiation primary Response
88 (MyD88) in mice. These results indicate that curcumin exerts an anti-inflammatory effect in
H. pylori-infected mucosa [102].
3.3. Curcumin in Neurological Disease
The World Health Organization (WHO) has defined neurological disorders as different pathologies
of the central and peripheral nervous system, including the brain, spinal cord, cranial nerves, peripheral
nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles. These disorders
produce epilepsy, Alzheimer disease (AD), Parkinson’s disease (PD), migraine, brain tumors and
traumatic disorders of the nervous system.
Curcumin can interact and modulate many molecular targets such as transcription factors,
inflammatory cytokines, kinases, growth factors and antioxidant system. All these actions of curcumin
will be responsible, at least in part for its neuroprotective. Many of these beneficial effects mentioned
before have been demonstrated by several paths in different types of cells from the nervous system,
such as neurons [
103
], astrocytes [
104
] and microglia [
105
]. Some researchers employing primary cell
cultures from different regions of the nervous system have also observed the capacity of curcumin
to act as neuroprotector due to its antioxidant, anti-inflammatory and anti-protein aggregating
properties [106] in cortical [105], mesencephalic [107], hippocampal [108] and spinal cord cells [109].
Furthermore, the capacity of curcumin to decrease neuro-inflammation, which takes place in the
progression of neurodegenerative diseases, by reducing the expression of IL-1
α
, IL-6 and TNF-
α
in
LPS-stimulated BV2 microglia in a dose dependent manner has been well established [
77
]. AD shows
signs of defective phagocytosis that results in an ineffective clearance of A
β
plaques. Curcumin can
stimulate microglial phagocytosis and clearance of A
β
plaques
in vitro
and increase the induction of
heat-shock proteins in response to the addition of soluble A
β
aggregates to neuronal cell cultures [
110
].
It also can attenuate the
β
-amyloid accumulation and inhibit the formation of A
β
fibrils in these
cells [
111
].Moreover,in dopaminergic neurons, neurotoxicity triggered by 6-hydroxydopamine
(6-OHDA) curcumin attenuated the toxicity in SH-SY5Y and MES23.5 cells through the inhibition of
ROS, mitochondrial protection and anti-apoptotic mechanisms [112,113].
Several studies in rodents have proved the neuroprotection of curcumin in neurodegenerative
disorders, especially AD and PD. Curcumin can also attenuate oxidative injury, microgliosis,
synaptophysin loss, spatial memory deficits, postsynaptic loss, and A
β
deposits produced by
intra-cerebral ventricular infusion of A
β
amyloid in rats [
114
]. Moreover, a study performed in
Tg2576 mice (a transgenic mouse model for AD) fed curcumin described a decrease of amyloid plaque
formation ROS and reactive nitrogen species (RNS) formation [
115
]. Finally, in mice overexpressing
A
β
(PS1dE9) where curcumin was intravenously administered, a plaque disruption and an attenuation
of distorted neuritis were found [116].
Molecules 2016,21, 264 7 of 22
In regards to PD, other studies have tested the neuroprotective potential of curcumin
against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-OHDA-induced dopaminergic
degeneration. Oral and intravenous administration of curcumin were able to modulate dopaminergic
damage in 6-OHDA-treated rodents, suppressing apoptosis, inducing microglial activation and
improving the locomotion [
117
]. Other studies performed with CAG140 mice described a powerful
capacity of curcumin to decrease Huntington protein aggregation, improving rearing deficits, but
impairing climbing behavior [
118
]. A study in
β
-amyloid-infused rats showed that curcumin improved
spatial memory [
119
]. Mechanisms through which curcumin can improve memory in AlCl
3
-challenged
mice is decreasing oxidative stress and histopathological damage in brain [120,121].
3.4. Role of Curcumin in Lung Injuries
Respiratory diseases are a complex group of disorders in the respiratory system, from the upper
tract into the pleural cavity, including both muscles and the nervous systems that modulates it.
The most studied pulmonary pathologies are fibrosis, bronchitis, allergy and asthma in relation with
inflammatory process and redox status alterations. The effects of curcumin in these process are
decreasing inflammatory cells accumulations [
122
], cytokines over-production [
123
] and increasing
ROS scavengers [52].
In 1996, the first evidence that curcumin has effects against pulmonary injuries was described
by Thresiamma et al. [
124
] using a radioactive curcumin administered orally in mice. Further studies
demonstrated the effect of curcumin in many pulmonary injuries [125127].
Pulmonary fibrosis is characterized by an accumulation of inflammatory cells in the airways [
125
].
These cells can generate a high increase in the cytokines, ROS and growth factors which promote in
turns the basis of the fibrotic scar. In this sense, several studies performed in animal models have
demonstrated that curcumin acts against pulmonary fibrosis mainly by decreasing the inflammatory
mediators [
126
,
127
]. Venkatesan and Chandrakasa [
128
] showed the beneficial effects of curcumin
against cyclophosphamide-induced pulmonary fibrosis in rats. These effects were a reduction in
leukocytes and inflammatory mediators and an increment in lung antioxidant defences. Similar
results were obtained by Venkatesan [
129
] who also described that rats injected with paraquat, to
provoked pulmonary fibrosis and treated with curcumin had a lower inflammatory response, toxicity
and mortality associated to this herbicide.
Asthma is a chronic inflammatory disease identified by a reversible airflow obstruction and
bronchospasm with variable intensity. Asthma is also characterized by goblet cell hyperplasia,
airway eosinophilia, mucus hypersecretion and hyperresponsiveness to endogenous and exogenous
allergens [
130
]. Several transcription factors are involved in the inflammatory process of asthma, including
the NF-
κβ
, AP-1, cyclic AMP response element binding protein, peroxisome proliferator-activated receptor
(PPAR) and the bZIP transcription factor, Nrf2 [
131
,
132
]. Eosinophils play a critical role in asthma by
producing inflammatory mediators and free radicals [
133
]. In this sense, there are critical interleukins
involved in the activation process of eosinophils such as IL-5, as well as IL-4 but in a lesser degree [
134
].
Their control can be considered as a novel strategy against asthma [135].
Curcumin has been widely used in ancient Indian medicine for allergy and asthma treatment [
81
]
and currently, several studies have found that curcumin has a powerful activity both
in vitro
and
in vivo
against asthma. These effects are produced by an inhibition of IL-5, IL-4, IL-2, immunoglobulin (Ig) E2
production [136,137] and by decreasing the histamine effects in peritoneal mast cells from rats [138,139].
In addition, Oh et al. [
132
] demonstrated the ability of curcumin to inhibit NF-
κβ
production in
a dose-dependent form by the inactivation of I
κ
-B
α
and AKT in pathogen-free BALB/c mice and in
murine macrophage-like Raw264.7 cell line [67,140].
Other studies have described that curcumin can improve the elimination of nitric oxide and
decrease the nitric oxide synthase activity. This might be a mechanism of curcumin which could
prevent the bronchial inflammation in asthmatic patients [
83
,
141
]. In addition, curcumin can protect
against asthmatic mucus secretion and airway hyperresponsiveness through an increment of Nrf2
Molecules 2016,21, 264 8 of 22
and HO-1 levels in lung [
94
]. In summary, all these beneficial effects of curcumin against asthmatic
pathologies and others lung injures immune-, ROS- and inflammation-associated [142144].
3.5. Relationship between Metabolic Syndrome and Curcumin
According to the American Heart, Lung and Blood Institute (NHLBI) metabolic syndrome is
defined as a “group of risk factors that raises your risk for heart disease and other health problems, such
as diabetes and stroke”. All risk factors are closely linked to obesity, to insulin resistance, lifestyle and
diet. For this reason the metabolic syndrome is also called “The Deadly Quartet” of hyperglycaemia,
hypertriglyceridemia, hypertension, and obesity [
145
] and the concurrence of all these together for a
long time, finally leads to cardiovascular diseases and diabetes type II [146].
Currently, inflammation is recognized as an overwhelming burden on healthcare status [
147
].
It is known that an increase of pro-inflammatory molecules (TNF-
α
, IL-6, MCP-1, and IL-1) directly
secreted from adipocytes is related to insulin resistance and chronic inflammation [148,149].
In the study performed by Rains et al. [
150
], the authors observed that curcumin has
immunomodulatory effects in obesity and insulin resistance because it decreases cytokines, TNF-
α
,
MCP-1, glucose and glycosylated haemoglobin in diabetic rats [151,152].
Another study employing C57BL/Ks-db/db diabetic mice demonstrated that curcumin decreased
blood glucose and glycosylated haemoglobin levels and increased the plasma insulin levels and
hepatic glucokinase activity. In addition, curcumin decreased the glucose-6-phosphatase and
phosphoenolpyruvate carboxykinase activities reducing glucose levels in blood [
153
] and improving
the glucose tolerance.
On the other hand, curcumin also decreased plasma free fatty acid, cholesterol, and triglyceride
levels and increased hepatic glycogen and skeletal muscle lipoprotein lipase (LPL) [
153
,
154
].
Kaur et al.
[
155
] in a study with an extract of curcumin, piperine and quercetin (both of them to
enhance the bioavailability of oral curcumin) showed that diabetic rats fed a high fat diet showed
decreased plasmatic levels of glucose, triglycerides, total cholesterol and low density lipoprotein (LDL)
with a concomitant increase high density lipoprotein (HDL).
Moreover, the decrease in plasma free fatty acid by curcumin in diabetes also promotes lower
lipotoxicity, considered as a trigger of insulin resistance through activation of NF-
κβ
[
156
]. In relation
to obesity, curcumin reduces body weight gain and angiogenesis in adipose tissue, decreases
pre-adipocytes differentiation and lipid accumulation in mature adipocytes in mice [
157
] favouring
the non-appearance of one of the risk factors of metabolic syndrome triggers [158,159].
All these results corroborate the powerful activities of curcumin appeasing hyperlipidaemia,
insulin resistance and glucose tolerance associated with excess dietary fat intake, obesity, and type 2
diabetes [155,160].
Finally, several clinical trials have been performed in humans with metabolic syndrome employing
both curcumin and curcuminoids. In these studies curcumin reduced lipid profile and modified
cholesterol-related parameters [
161
,
162
]. Furthermore an study suggests the relevance of curcumin
improving the anthropometric measurements and body composition when it is associated to diet and
lifestyle intervention [163].
3.6. Curcumin as Hepatoprotective
The liver is intensely involved in the metabolism and synthesis of all macronutrients and it
presents highly relevant endocrine and exocrine functions. The liver is also responsible for the
detoxification of the blood. The liver has a very complex architecture and present different types of
cells such as hepatocyte, cholangiocyte/bile duct cell, endothelial cell, liver sinusoidal endothelial
cell, pit cell, Kupffer cell and hepatic stellate cell [
5
,
164
]. All activities performed by the liver are
highly relevant for life and for this reason, when liver diseases appear, these functions are substantially
compromised, with a resulting increase in morbidity and mortality [164].
Molecules 2016,21, 264 9 of 22
The beneficial effects of curcumin in liver diseases can be due to its anti-inflammatory, antioxidant
effects and antifibrogenic properties [
165
]. In addition, curcumin can decrease levels of thiobarbituric
acid reactive substances (TBARS) and increase GSH and SOD levels in the liver homogenates from
LPS-challenged rats supplemented with curcumin [
166
]. Curcumin also reduces the iron-induced
hepatic damage by lowering lipid peroxidation [
45
,
46
], increase the activity of xenobiotic detoxifying
enzymes [
47
] and the hepatic total antioxidant capacity [
48
]. Finally, this molecule can up regulate the
cytoprotective enzyme HO-1 [167] inhibiting the ROS formation in liver [49].
In this sense, some studies carried out by our research group [
168
] have demonstrated that
curcumin decreased the non-alcoholic steatohepatitis (NASH) and aminotransferase activity, and
increased the mitochondrial antioxidants in rabbits with high-fat-induced NASH. Moreover, curcumin
also reduced mitochondrial ROS, improved mitochondrial function, and lowered levels of TNF-
α
. All
these results were corroborated by Wang et al. [169] in a rat model.
According to the hepatoprotective effects of curcumin, there are studies which have described a
down-regulation of NF-
κβ
transcription factor [
170
], an improvement of hepatic fibrosis in alcoholic
liver injuries [
171
], an increase of the survival rates in animals [
172
] and a reduction of damage in
experimental steatohepatitis [173].
3.7. Has Curcumin Got an Antitumor Effect?
Regarding the antitumor properties of curcumin, they are a lot of studies carried out in animals,
human leukaemia cell types [
12
], and several clinical trials in cancer patients. Only few of them
have described the anticancer potential of curcumin [
20
,
174
] and many of them have investigated the
capacity of curcumin as an adjuvant in anti-tumour therapy or reducing adverse effects associated
with the treatment [
174
178
]. In this sense, Sharma et al. [
179
] showed that curcumin prevent colon
cancer in rodent model by inhibition of lipid peroxidation and cyclooxygenase-2 (COX-2) expression
and by increase of glutathione S-transferase (GST) enzymes [180].
On the other hand, ROS and inflammation are linked to carcinogenesis processes [
71
,
181
], mainly
acting as initiators in the well-known triphasic theory of cancer: initiation, promotion and progression
(Figure 4). For this reason, some anticancer properties of curcumin are due to the antioxidant and ROS
scavenger activities already described before. Moreover, the effects of curcumin in different genes
and proteins such as Bcl-2, VCAM-1, Cyclin D1, Bax, NF-
κβ
, VGEF or COX-2, curcumin prevents the
promotion and progression stages [
182
]. Hosseini and Ghorbani [
183
] have described the anticancer
effects of curcumin by multiple actions on mutagenesis, cell cycle regulation, apoptosis and oncogene
expression. However, curcumin also can modulate different pathways related to angiogenesis, invasion,
tumour growth or metastasis [
184
] and it can promote apoptosis through interaction with p53 [
185
],
caspase expression [186], and inducing cell cycle arrest [187].
Figure 4. The three steps in the carcinogenesis process: initiation, promotion and progression.
Molecules 2016,21, 264 10 of 22
Several epidemiological studies have determined that inflammation is one of the most important
risk factors associated to carcinogenesis. During this process, the activation and interaction between
NF-
κβ
and STAT3 has been identified as a key mechanism in the communication between cancer
cells and inflammatory cells [
188
]. As has already been described previously, curcumin is able to
down-regulate different pathways related to both molecules, then decreasing the generation of different
inflammatory mediators such as COX-2, lipoxygenase 2 (LOX-2), iNOS, and cytokines associated to
them and hence preventing the carcinogenesis process in several types of cancer [189191].
In addition, curcumin inhibits JAK-STAT pathway [
192
] and inhibits telomerase activity [
193
],
finally driving to the arrest of cell cycle and apoptosis in tumour cells.
Regarding to breast cancer, curcumin has demonstrated similar results by inhibition of
COX-1, COX-2, Bax expression, vascular endothelial growth factor (VEGF) and the telomerase
activity
[71,194,195]
. Curcumin also downregulates the inflammatory cytokines CXCL1 and CXCL2 by
the inhibition of NF-κβ [196].
In human lung cancer cells, curcumin has similar mechanisms decreasing the migration and
invasion of cells through inhibition of MMP-2 and MMP-9 and suppression of VEGF expression [
197
].
In this sense, Das and Vinayak [
198
] described how curcumin regulates genes as hypoxia-inducible
factor 1-alpha (HIF-1a) and MYC, LDH activity and decreases the angiogenesis process by a MMP-2,
MMP-9, PKC-a and VEGF reduction. All these results are in accord with studies performed in a
lung cancer mice model which also showed that curcumin can inhibit the neutrophil chemoattractant
keratinocyte-derived chemokine expression (CXC-KC) stopping the tumour progression [199].
Finally, several cytokines have been focused as target for prevention and treatment of several
types of tumours [
200
202
]. In this sense, curcumin can inhibit some of these cytokines such as IL-1
β
,
IL-6, TNF
α
or IL-23 so this molecule has an important role in cancer that overexpress them such as
oral cavity, forestomach, duodenum, and colon [203].
3.8. How Does Curcumin Prevent Cardiovascular Pathologies?
According to the definition proposed by the World Health Organization, cardiovascular diseases
(CVDs) are a complex group of disorders that affect the heart and blood vessels. These disorders
are associated with risk factors such as an unhealthy diet, physical inactivity, tobacco use and use
of alcohol. There are many signs and symptoms of these disorders as raised blood pressure, raised
blood glucose, raised blood lipids, and excess weight and obesity. One of the most important causes
of stroke and heart attacks is atherosclerosis. This is a complex and multistep process with many
factors involved in the formation and evolution of the atherosclerotic plaque. Lipoprotein oxidation
and oxidative processes play a critical role in the pathogenesis atherosclerosis. Some studies have
identified the oxidized LDL (ox-LDL) as a powerful atherogenic agent [204,205].
Several mechanisms have been proposed by which ox-LDL can develop the atherogenic process
such as the enhanced uptake by macrophages which leads to foam-cell formation, cytotoxic actions
and alteration of platelet aggregation mechanism [206,207]. In this sense, some studies performed by
our research group, have demonstrated the effectiveness of a curcumin extract to downregulate the
LDL and ox-LDL concentration and also increase the HDL level by decreasing the oxidative stress and
attenuating aortic fatty streak development in a rabbits fed a high cholesterol diet [
208
,
209
]. In addition,
curcumin also exhibits an inhibitory effect on the platelet aggregation and eicosanoid metabolism,
showing its cardio protective character [
210
]. In a coronary artery disease study performed in humans,
curcumin was able to decrease, very low density lipoprotein (VLDL), LDL cholesterol and serum
triglyceride with no effect on inflammatory biomarkers [211].
The strong association between cardiovascular diseases risk and inflammation has been
well established [
207
,
212
,
213
]. As has been described before, curcumin decreases the levels of
inflammatory molecules such as TNF-
α
, p38 MAPK, JAK2/STAT3 so it improves cardiovascular
risk inflammation-associated [
214
,
215
]. Moreover, curcumin suppress the activation of TLR4, inhibits
Molecules 2016,21, 264 11 of 22
phosphorylation of ERK1/2 and nuclear translocation of NF-
κβ
and reduces nicotinamide adenine
dinucleotide phosphate (NADPH)-mediated intracellular ROS production [216].
In relation to cardioprotective effects associated to oxidative stress, curcumin attenuates oxidative
stress by up-regulating eNOS expression, decreasing p47phox NADPH oxidase and superoxide
generation the vascular tissues. All these effects promote a descent of blood pressure and hind
limb vascular resistance and increased hind limb blood flow [
217
]. In addition, curcumin increases
Nrf2 expression and inhibits NF-
κβ
activation in an obesity-induced heart injury both in
in vivo
and
in vitro
models [
218
]. In 5/6 nephrectomised rats curcumin also promoted the Nrf2 activation, and
prevented of hemodynamic changes and glomerular hypertension [219,220]. In the study carried out
by Abo-Salem et al. [
221
], curcumin increased cardiac antioxidant enzymes such as catalase, SOD,
glutathione-S-transferase and glutathione reduced in streptozotocin-induced heart injury in rats.
Finally, curcumin can also act as cardioprotector in an ischemia reperfusion injury model. This
effect is produced because curcumin can activate SIRT1 signalling which reduces mitochondrial
damage. SIRT1 reduces some molecules as SOD, succinate dehydrogenase, cytochrome c oxidase,
methane dicarboxylic aldehyde and H
2
O
2
levels in mitochondria [
222
]. In summary, the natural
cardioprotective activity of curcumin is in part due to a reduction of the oxidative stress.
4. Conclusions
Through this review, the beneficial effects of curcumin against different diseases highly relevant
in modern societies has been proved. In summary it can be concluded that curcumin has protective
health effects mainly through anti-inflammatory and antioxidant mechanisms. Thus, curcumin has
an important role against neurological, cancer, cardiovascular and lung diseases, and also against
metabolic syndrome and liver disorders. Likewise, several specific mechanisms of action have been
postulated for curcumin, to understand its beneficial effects and its role as a nutraceutical compound.
Author Contributions:
All authors have participated actively in the conception and design of the review. They also
have stablished different points of view about the molecule studied and its role in health, being inescapable
part in this study. M.C. Ramirez-Tortosa and Cesar Ramirez-Tortosa have also participated in the paper revision
and interpretation. M. Pulido-Moran and Jorge Moreno-Fernandez have written this paper and have actively
participated in the revision and conceptualization of the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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... leaf extract showed the lowest increase in TBARS value in comparison to the control (without wrapping) [12]. According to Lee et al. [78], the storage duration significantly influenced the lipid oxidation in meat, but there is an inhibitory effect on the oxidation in food products with EF, the antioxidant properties of APE, and its ability to block oxygen, particularly due to its high polyphenol content [79]. It has also been reported that APE have antioxidant properties due to the active compounds such as phenolics and flavonoids [80]. ...
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Asian plants (AP) have long been used as natural food preservatives in the food industry. Asian plant extracts (APE) and essential oils (EOs) with antioxidant and antimicrobial properties were incorporated into edible film (EF) for the inhibition of microbial growth in the food matrix. However, information on the utilization of these antibacterial EFs on the storage application of different local food products has not been thoroughly reviewed. Hence, this review gives an overview of the physicochemical, mechanical, antioxidant, and antibacterial properties of EF incorporated with AP and their storage application for the preservation of food products. For their applicability as food packaging, the potency of these EFs to be used as food packaging in preventing food spoilage or foodborne pathogens was also thoroughly reviewed. The addition of APE and EOs into the packaging matrix demonstrated the potential to prolong the storage of food products by preserving food quality (pH, colors, and lipid oxidation) and safety during storage, and the inhibition zones of some extracts against the pathogens demonstrated are weaker in comparison to the standard antibiotic drug used (WHO standards). In conclusion, the freshness of food products could be retained and lengthened by using EF with APE and Eos as active edible food packaging. However, additional research is required to significantly improve its antibacterial activity, producibility, and technical feasibility for long-term market use.
... Numerous human clinical and animal studies have shown the health benefits of curcumin. Historically they include antioxidant, anti-inflammatory, immunoprotective, antimicrobial, antineoplastic, antidepressant, and neuroprotective activities [1,2,3,4,5,6,7,8]. More recently curcumin has also been explored as a treatment for neuropsychiatric and neurodegenerative diseases [9,10,11,12]. ...
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Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ 13 C) and nitrogen (δ 15 N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ 13 C and δ 15 N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ 13 C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ 15 N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability.
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Turmeric (Curcuma Longa) is a type of herb belonging to ginger family, which is widely grown in southern and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran, Malesia, India, China, Polynesia and Thailand, is often used as spice and has an effect on the nature, color and taste of foods. Turmeric is also known to have been used for centuries in India and China for the medical treatments of such illnesses as dermatologic diseases, infection, stress and depression. Turmeric's effects on health generally are centered upon an orange-yellow colored, lipophilic polyphenol substance called 'curcumin', which is acquired from the rhizomes of the herb. Curcumin is known recently to have antioxidant, anti-inflammatory, anti-cancer effects and, thanks to these effects, to have an important role in prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological, cardiovascular diseases and diabetic. Furthermore, it is aimed to increase the biological activity and physiological effects of the curcumin on the body by synthesizing curcumin analogues. This paper reviews the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological activities and effects on health of curcumin.
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Purpose of review Acute pancreatitis is associated with a significant morbidity and a mortality as high as 10%. This review summarizes the most relevant articles in the past year that have contributed to understanding and management of this disease. Recent findings Pathologic activation of both digestive zymogens and the transcription factor nuclear factor kappaB are early events in acute pancreatitis; these pathologic processes are inhibited in experimental pancreatitis by curcumin and the pH modulator chloroquine. Primary sensory neurons may constitute a final common pathway for pancreatic inflammation. Experimental acute pancreatitis and associated lung injury are attenuated by inhibiting the prostanoid mediators cyclo-oxygenase-2 and 5-lipoxygenase and CC chemokine receptor antagonist Met-RANTES. Endoscopic retrograde cholangiopancreatography-induced acute pancreatitis can be reduced experimentally by intraductal neurokinin-1 receptor antagonist and clinically by use of diclofenac and pancreatic duct stenting. MRI in the setting of acute pancreatitis is a reliable method of staging disease severity, Distinct patterns of cytokine response are observed in acute pancreatitis. Summary Early events within the acinar cell and the regulation of inflammation by transcription factors continue to be elucidated Although experimental acute pancreatitis can be successfully ameliorated by use of cytokine and inflammatory inhibitors, this has not been demonstrated in clinical disease. The finding of a compartmentalization of the inflammatory response in acute pancreatitis may be important for planning therapeutic interventions. Pancreatic duct stenting reduces the risk of developing postendoscopic retrograde cholangiopancreatography pancreatitis in high-risk people.
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Background: Non-alcoholic fatty hepatitis (NASH) is highly prevalent, mitochondria damage is the main pathophysiological characteristic of NASH. However, treatment for mitochondria damage is rarely reported. Methods: NASH model was established in rats, the protective effects of curcumin were evaluated by histological observation; structure and function assessments of mitochondria; and apoptotic genes expression. Results: NASH rats treated with curcumin displayed relatively slight liver damage when compared with NASH livers. The average mitochondrial length and width of NASH (12.0 ± 3.2 and 5.1 ± 1.1 micrometers) were significantly longer than that of normal (6.2 ± 2.1 and 2.1 ± 1.5 micrometers) and NASH treated with curcumin (7.4 ± 1.2 and 3.2 ± 1.5 micrometers) rats. The average malondialdehyde (MDA) and 4-hydroxy nonyl alcohol (HNE) levels in liver homogenates of NASH rats (4.23 ± 0.22 and 19.23 ± 2.3 nmol/Ml) were significantly higher than these in normal (1.32 ± 0.12 and 3.52 ± 0.43 nmol/mL) and NASH treated with curcumin (1.74 ± 0.11 and 4.66 ± 0.99 nmol/mL) rats. The expression levels of CytC, Casp3 and Casp8 of the NASH livers were significantly higher than normal and NASH treated with curcumin rats livers. Conclusion: Our data demonstrated that curcumin prevents the NASH by mitochondria protection and apoptosis reduction and provided a possible novel treatment for NASH.
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Objective: This randomized, controlled study aims to evaluate the tolerability and the efficacy of curcumin in overweight subjects affected from metabolic syndrome, with a focus on impaired glucose intolerance and android-type fat accumulation. Patients and methods: Forty-four subjects, selected among those who after 30 days of diet and intervention lifestyle have shown a weight loss < 2%, have been treated for further 30 days either with curcumin complexed with phosphatidylserine in phytosome form or with pure phosphatidylserine. Outcomes concerning anthropometric measurements and body composition were analyzed at enrollment and after 30 and 60 days. Results: Curcumin administration increased weight loss from 1.88 to 4.91%, enhanced percentage reduction of body fat (from 0.70 to 8.43%), increased waistline reduction (from 2.36 to 4.14%), improved hip circumference reduction from 0.74 to 2.51% and enhanced reduction of BMI (from 2.10 to 6.43%) (p < 0.01 for all comparisons). Phosphatidylserine did not show any statistical significant effect. Tolerability was very good for both treatments, and no drop-out was reported. Conclusions: Although preliminary, our findings suggest that a bioavailable form of curcumin is well-tolerated and can positively influence weight management in overweight people.
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An Ethyl acetate (AcOEt) extract from the rhizome of Curcuma longa L. has preventive activities in experimental models of allergy types I and IV. The purpose of the present study is to clarify the features of inhibitory actions of the AcOEt extract on the histamine release from rat mast cells (allergy type I) and to compare the effect with that of curcumin. At a concentration of 50 μg/ml, both the AcOEt extract and curcumin inhibited the histamine release induced by concanavalin A, and also suppressed the histamine release induced by compound 48/80, in the absence or presence of Ca2+ and that induced by A23187. In the experiment of two stage models, they markedly reduced the histamine release when administered prior to and posterior to the addition of concanavalin A. The effect of the AcOEt extract on the inhibition of histamine release was somewhat stronger than that of curcumin. These findings suggest that 1) the AcOEt extract potently suppresses the histamine release probably through the blockage of the degranulation process following a rise in intracellular Ca2+ levels induced by the three types of histamine releasers, and 2) the features of the actions of the AcOEt extract are similar to those of curcumin.
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Hydroxytyrosol is a polyphenol that forms part of the minor compound fraction of extra virgin olive oil, one of the most important elements in the Mediterranean diet. Because of the low incidence of different diseases in Mediterranean countries, such as cardiovascular diseases and cancer, plenty of studies have been performed showing which components of this healthy diet are responsible for these beneficial effects, and most of them have reported that hydroxytyrosol is one of these components. Because of the nature of this element, many studies of this isolated component have been performed using different hydroxytyrosol-enriched olive oils. This research has demonstrated hydroxytyrosol's potential as an antioxidant, anti-inflammatory, and antiatherogenic agent and its role in the prevention of different diseases, together with some other direct activities such as antitumor action or as an inhibitor of the expression of different cellular receptors. In addition, a relation with the expression of some specific proteins involved in many diseases has been documented in the scientific literature. Other studies have focused on its antimicrobial and dermatological activities and its importance in healing and epithelization after surgery. All these findings allow a possible role as a nutraceutical in the prevention and treatment of some pathologies to be postulated.