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Curcumin, a yellow substance derived from the Rhizoma Curcumea Longae, is the main constituent of the spice turmeric. It is a lipophylic polyphenol, a bis-alpha,beta-unsaturated beta-diphenone with the chemical formula C21H20O6 and chemical name of (E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5 dione). There are numerous studies documenting curcumin's anti-inflammatory and anti-diabetic properties, among which the inhibition of inflammatory cytokines, such as MCP and TNF-a along with the induction of AMPK through inhibition of MAPK play a pivotal role in its mechanisms of action. In this review, the anti-diabetic properties of curcumin and its potential beneficial effects in the prevention and treatment of diabetes mellitus will be discussed.
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CURRENT TOPICS IN NUTRACEUTICAL RESEARCH Vol. 12, No. 4, pp. 135-142, 2014
ISSN 1540-7535 print, Copyright © 2014 by New Century Health Publishers, LLC
www.newcenturyhealthpublishers.com
All rights of reproduction in any form reserved
CURCUMIN AND DIABETES: MECHANISMS OF ACTION AND ITS ANTI-DIABETIC
PROPERTIES
1Christos Kazazis, 2Natalia G. Vallianou, 2Aris Kollas and 3Angelos Evangelopoulos
1Internist, Horonary Lecturer at Leicester University, Samos, Greece; 2Internist, Evangelismos General Hospital, Athens,
Greece; and 3Biologist, Roche Diagnostics, Athens, Greece
[Received May 27, 2014; Accepted July 29, 2014]
[Communicated by Arrigo F.G. Cicero, MD, PhD]
ABSTRACT: Curcumin, a yellow substance derived from the
Rhizoma Curcumea Longae, is the main constituent of the spice
turmeric. It is a lipophylic polyphenol, a bis-a ,b-unsaturated
b-diphenone with the chemical formula C21H20O6 and
chemical name of (E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-
1,6-heptadiene-3,5 dione). ere are numerous studies
documenting curcumin’s anti-inflammatory and anti-diabetic
properties, among which the inhibition of inflammatory
cytokines, such as MCP and TNF-a along with the induction
of AMPK through inhibition of MAPK play a pivotal role
in its mechanisms of action. In this review, the anti-diabetic
properties of curcumin and its potential beneficial effects in the
prevention and treatment of diabetes mellitus will be discussed.
KEY WORDS: AMPK, Curcumin, Diabetes, Inammation,
Obesity
Corresponding Author: Natalia G. Vallianou, MD, PhD, 5
Pyramidon str, Municipality of Marathon, 190 05 Athens,
Greece; E-mail: natalia.vallianou@hotmail.com
INTRODUCTION
Diabetes mellitus constitutes a major public health threat,
especially in low and middle-income countries, as it was
estimated that in 2013 382 million people suered from the
disease, while this number is expected to rise to 592 million by
year 2035, according to the IDF. Obesity is an inammatory
process that includes, among other things, increased production
of adipokines as well as increased and decreased production
of pro and anti-inammatory cytokines, respectively; thus,
contributing to the development of type 2 diabetes mellitus and
cancer (Lee et al., 2013). In this paper, we will discuss the anti-
inammatory and possible anti-diabetic eects of a herb used in
traditional Chinese and Indian medicine- Rhizoma Curcumea
Longae and -in particular- one of its active components derived
from turmeric, curcumin (Xie and Du, 2011).
Curcumin 1, the main constituent of turmeric, is a lipophylic
polyphenol, a bis-α,β-unsaturated -diphenone with the
chemical formula C21H20O6 and chemical name of (E,E)-1,7-
bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5 dione).
While it is not soluble in water, it demonstrates considerable
stability in the stomach’s acidic environment, especially when
it is administered with anti-oxidants like vitamin C. ere are
numerous studies documenting curcumins anti-inammatory,
anti-diabetic and anti-cancerous properties (Basnet et al.,
2011; Shehzad et al, 2013; Zhang et al, 2013).
Transition from normal weight to obesity leads to appearance
of a low-grade chronic inammation, which plays cardinal
role in the development of type 2 diabetes mellitus. e
hypertrophic adipose tissue is characterized by large adipocytes,
resistant to insulin, and activated macrophages. Furthermore,
decreased production of anti-inammatory molecules, like
adiponectin, and increased production of inammatory ones,
namely leptin, resistin, IL6, MCP-1, TNF-α, PAI-1, Ang II
takes place. Primary mediators for adipose tissue inammation
are toll-like receptors (TLRs) and nuclear factor-κΒ (NF-κB).
e former activates the latter leading to transcription of
inammatory cytokines like IL-6 and TNF-α (Siriwardhana
et al., 2013).
AGEs also play a role in inammation. ey are the result
of glucose interaction mainly with proteins and to a lesser
extent with nucleic acids. Hyperglycemia results in increased
production of AGEs with deleterious eects inside the cell
and the extra-cellular matrix. AGE receptors also play a role
in the inammatory process, as they have been identied
on monocytes and macrophages, and their activation leads
to production of inammatory cytokines from the latter.
AGE receptors have been also recognized on glomerular
mesangial and vascular endothelial cells and are responsible for
production of reactive oxygen species as well as activation of
NF-κB and p21 ras (Goldstein et al., 2010).
136 Curcumin and diabetes
IN VITRO DATA
Experimental exposure of endothelial and Jurkat
T-lymphoblasts to conditions mimicking diabetes mellitus
(high glucose levels or AGE) and subsequent study of curcumin
action on cell membranes have demonstrated a benecial
eect on membrane uidity and transmembrane potential,
resulting in reduction of inammation, by inuencing levels
of lipid peroxidation and MCP-1 release (Lin et al., 2012).
Curcumin inhibits formation of inammatory cytokines
(MCP, IL-6, TNF-α) either directly or through inhibition
of NF-κB and PGE2. Besides, its benecial eect on
inammation is demonstrated by induction of AMPK and
inhibition of MAPK (Siriwardhana et al., 2013). Curcumin
and dimethoxycurcumin in particular inhibit AGE production
by trapping an AGE precursor-methylglyoxal- a mechanism
also identied in other polyphenols (Lin et al., 2012).
ere is mounting evidence that curcumin plays a protective
role against non-alcoholic steatohepatitis, which often
accompanies type 2 diabetes mellitus, through induction of
AGE-R1 gene expression, leading to clearance of AGEs from
the liver. is is achieved in hepatic stellate cells by inhibition
of extracellular signal-regulated kinase (ERK) activity,
induction of gene expression of PPAR-γ, and stimulation
of its transactivity (Jianguo et al., 2012). In the same cells,
it suppresses RAGE gene expression, mainly by interrupting
the p38 MAPK signaling pathway, canceling in that way
membrane translocation of glucose transporter-2 (GLUT2),
and by stimulating PPARγ activity and de novo synthesis of
GSH resulting in suppression of GLUT2 expression (Margina
et al., 2013). Moreover, gluco-conjugates are crucial for life
maintenance polymers of sugars with proteins or lipids.
eir increased hydrolysis involving lysosomal enzymes,
correlates with the levels of oxidative stress, AGE production
and microvascular complications in diabetes mellitus. It is
undeniable that there is a tight link between diabetes and
immune dysfunction (Sparks et al., 2012). On the other hand,
obesity causes endoplasmic reticulum stress, with subsequent
activation of the inammatory cascade, via activation of several
kinases including the c-Jun N-terminal kinase (JNK), leading
to insulin resistance and eventually diabetes (Siriwardhana et
al., 2013).
Curcumin seems to be a potent immune-modulator, as it
promotes apoptotic cell death of activated Jurcat T-cells, by
increasing endoplasmic reticulum stress response, making it
an attractive candidate for treatment of several autoimmune
diseases and diabetes (Zheng et al., 2013).
Accumulation of amyloid in the pancreas, with amylin as
its major component, up-regulated by MCP-1 through JNK,
ERK and NF-κΒ signaling, is also recognized as a factor
contributing to the appearance of insulin resistance and type
2 diabetes (Gota et al., 2010). Curcumin interferes in the
amyloid’s self-assembly, by disassembling the α-helix of the
molecule (Sparks et al., 2012).
A recent study has documented that curcumin signicantly
increases GLP-1 secretion in GLUTag cells in a Ca/Ca
calmodulin-dependent kinase pathway, which is independent
of c-AMP/PKA, PKC and MEK/ERK pathways (Cuomo et
al., 2011). e increased secretion of GLP-1 may be another
mechanism, by which curcumin exerts its anti-hyperglycemic
eects.
Nanocurcumin (curcumin encapsulated PLGA
nanoparticles) demonstrated a better performace in comparison
with curcumin, as far as delay of cataract development is
concerned, in four dierent ways: a) by preventing MDA and
protein carbonyl levels to rise b) by normalizing AR activity
(an enzyme playing a critical role in the polyol pathway) and
subsequently reducing sorbitol levels c) by reducing AGE
formation in soluble protein fraction and d) by improving the
total and soluble protein levels, as protein in-solubilization
is the nal step to lens opacication and cataract (Cai et al.,
2011).
In addition, curcumin is a protein kinase C-a, PKC-β
and ERK1/2 activity suppressor and acts similarly as far as
expression of TGF-β1, CTGF, osteopontin, p300, bronectin
and type IV collagen is concerned (Takikawa et al., 2013).
Furthermore, there is data indicating that curcuming
reduces neuropathic pain by activating the opioid receptors
(Antony et al., 2008). Neuropathic pain, demyelination, nerve
ischemia and reduction of inammation (mainly by inhibiting
phosphorylation of IKK complex and subsequent activation
of NF-κΒ) was augmented by using a SNEDDS curcumin
formulation. is was due to its enhanced bioavailability
compared to the classical formulation, and was attributed to
its globule size, as well as its better dissolution and increased
absorption from the lymphatic system. ese properties were
achieved due to presence of gelucire 44/14, which improves
permeability by inhibiting eux of P-glycoprotein, and
to opening of the tight junctions in Caco-2 cells. On the
other hand, solubilization of curcumin micelles, inhibition
of the eux system, and reduction of curcumins intestinal
metabolism, occurred due to vitamin E TPGS in the SNEDDS
formulation (Gramma et al., 2013).
EX VIVO DATA
Despite small sample size (n < 30), a number of studies
has shown that curcumin-treated diabetic rats and diabetic
patients presented with statistically signicant reduction in
blood glucose levels and weight. Animal studies indicate that
curcumin signicantly increases plasma insulin levels and
decreases plasma glucose and glycated hemoglobin levels.
is was attributed to increased hemoxygenase activity in the
pancreas (Tables 1, 2).
Curcumin reduced lysosomal enzyme activity in diabetic
rats by over 65% (Yue et al., 2013). Curcumin seems to
contribute in the prevention of diabetic retinopathy by acting,
among other ways, as an antioxidant and anti-inammatory
agent as well as a VEGF inhibitor. Antioxidant properties are
demonstrated by preventing diabetes-induced decrease in the
retinal antioxidant capacity, inhibition of NF-κB activation
and accumulation of 8-OHdG and nitro-tyrosine, while levels
Curcumin and diabetes 137
of retinal glutathione, superoxide dismutase and catalase are
increased, when curcumin is administered at a dose of 1g/kg
body weight.
Curcumins anti-inammatory eects, besides those
mentioned above, are evident in down-regulation
of 5-hydroxy-eicosatetranoic acid, cyclooxygenase,
lipoxygenase and arachidonic acid metabolism.
Regarding curcumin’s eects on angiogenesis, it acts as
a VEGF inhibitor, as well as a VEGF-induced PKCβ II-
translocation inhibitor. In addition, curcumin decreases
levels of stromal cell-derived factor 1 (SDF-1).
Curcumin is also an inhibitor of transcription factor
EGR-1, which encodes a nuclear phospho-protein, vital
for control of several diseases, including diabetes. In this
way, EGR1 and the gene’s expression in endothelial cells,
broblasts and rat retinas is hindered (Wei et al., 2012).
In type 1 diabetic rats, curcumin has contributed
to the prevention of renal brosis by down-regulation
of sphingosine-kinase-1 activity and sphingosine-1-
phosphate production, as this pathway, under conditions
of hyperglycemia, favors overproduction of bronectin
(FN) and transforming growth factor beta (TGF-β). SphK1
expression is blocked due to curcumins inhibitory eect
on AP-1 transcriptional activity, and especially, its most
important constituent cJun (Soetikno et al., 2012; Chougala
et al., 2012).
In diabetic rats fed with curcumin at a dose of 100 mg/
kg/day, an approximately 30% reduction in macrophage
inux to the glomerulus was noted. is, was followed by a
twofold reduction in levels of activated NF-κB and reduced
rate of cytosolic IκBα degradation, resulting in reduction
of renal TNF-α and IL-1β mRNA expression by 1.7 and
2.5 fold, respectively. Curcumin has also down-regulated
expression of ICAM-1 and MCP-1 (Aldebasi et al., 2013).
ere is no doubt that accumulation of lipids in the
kidney plays an important role in the pathogenesis of
diabetic nephropathy. In diabetic rats, receiving per os the
same curcumin dose as above, a decrease in plasma and
renal triglyceride levels was noted. is, benecial for the
kidney, eect was attributed to curcumins activation of
AMPK, with subsequent suppression of renal regulatory
element-binding protein–1c (SREBP-1c), resulting in
decreased expression of acetyl-CoA-carboxylase, fatty acid
synthase and adipose dierentiation related protein, which
is a marker of triglyceride accumulation in the kidney. An
increase in nephrin expression was also documented (Patel
et al., 2013).
Curcumin is a NADPH-oxidase inhibitor, which is
activated in diabetic neuropathy. It has also reversed
increased MDA concentration and decreased SOD activity
in the spinal cord of STZ-induced diabetic rats, leading to
the reduction of neuropathic pain (Soetikno et al., 2013).
Curcumin has reduced hyperglycemia-induced direct
neuronal damage in rats treated with streptozocin, by acting
as a free radical scavenger in the cerebral cortex, due to its
phenolic -OH groups. Besides, by modulating muscarinic
cholinergic receptors and by down-regulating the α-7
nicotinic receptor and insulin receptor mRNA, it improved
their cognitive performance. Glucose uptake by the cerebral
cortex was also improved through control of increased
GLUT3 expression (Soetikno et al., 2011a).
Neuropathic pain, which is elicited with the help of
TNF-α, among other pro-inammatory cytokines, released
from activated microglia in the dorsal horn of the spinal
TABLE 1. Curcumin-induced changes in glucose levels of diabetic rats
Study Glucose
measured Control Diabetes Diabetes + Cur
100 mg/kg
Diabetes + Cur
150 mg/kg
Diabetes + Cur
200 mg/kg
Huang J, 2013 FBG 5.60±0.64 22.53±3.81 18.34±4.86
Aziz, 2013 FPG 5.06±0.38 16.88±1.73
10.56±0.35
(curcumin 20
mg/kg/d)
Na, 2013 (human
study) FPG 8.4±2.06
(Control group) 7.28±1.77
Yu, 2012 FBG 5.1±0.1 20.6±1.6 13.1±2.2 8.7±1.7
Soetikno, 2012 FPG 6.52±0.33 40.9±0.5 32.8±0.54
Soetikno, 2011 FPG 7.74±1.1 38.49±0.95 32.94±0.93
TABLE 2. Curcumin-induced weight changes in diabetic rats. All values are presented as mean ± S.E.M. C-control group, d – diabetic
rats, d + c – diabetic rats treated with curcumin
Study C D d + cur 100 mg/kg d + c 150 mg/kg d + c 200 mg/kg
Huang J, 2013 490±8.12 362.14±18.14 394.44±19.69
Yu, 2012 401±18 247±19 293±25 332 ± 27
Soetikno, 2011 541±15.05 328.6±12.63 353.2±16.55
Soetikno, 2011 539.5±19.24 325.8±15.98 341.5±15.11
138 Curcumin and diabetes
cord, was reduced in STZ-induced diabetic rats treated
with curcumin, as it was found that its administration
caused reduction in expression of TNF-α receptor, followed
by amelioration of mechanical allodynia and thermal
hyperalgesia (Kumar et al., 2011).
In diabetic rats with cardiomyopathy, curcumin seemed
to contribute in improvement of several echocardiographic
and histologic variables in a statistically signicant manner
in the curcumin treated diabetic rats (Table 4) (Hamind
et al., 2013). e cardiac muscle of STZ-induced diabetic
rats treated with curcumin at a dose of 100 or 200 mg/
kg/day, showed a marked improvement as far as left
ventricular dysfunction (increase in ejection fraction)
and intravetricular septal hypertrophy were concerned
(decreased IVSD). In addition, at the cellular level, it was
proven that curcumin restored histologic abnormalities in
the cardiomyocyte in conjuction with reduction in the rate
of glycogenolysis and reduced hypertrophy and brosis.
At the biochemical level, besides inhibition of markers of
inammation, AGE accumulation and RAGE expression,
decreased levels of myocardial injury markers (CK-MB,
LDH, AST) were noted in the 200 mg/kg/day treated
group. Moreover, cardiomyocyte apoptosis was prevented in
the same group through up-regulation of the anti-apoptotic
protein Bcl-2 and down-regulation of the pro-apoptotic Bax
and caspase-3 proteins. Also, curcumin-induced increased
phosphorylation of Akt and GSK-3β, played a benecial
role in cardiomyocyte’s growth and survival (Rayanta et al.,
2013). Last, but not least, in the cardiac muscle curcumin
acted as an inhibitor of NF-κB, decreased levels of NAD(P)
H oxidase, TGF-β, osteopontin, myocyte enhancer factor-2
and down-regulated protein kinase C-α and β2-mitogen
activated protein kinase (MAPK) pathway, as well as mRNA
expression of transcriptional co-activator p300 (which plays
an important role in cardiac hypertrophy and failure), atrial
natriuretic peptide, accumulation of ECM protein and
increased superoxide production in the left ventricle of
diabetic rats (Wei-Cheng et al., 2014).
Numerous studies on animals, provide insights on
curcumins benecial and statistically signicant eects on
renal function and potential underlying mechanisms (Table
3) (Soetikno et al., 2011b; Huang et al., 2013).
HUMAN STUDIES
Recently, a randomized, double-blind, clinical trial
assessed the ecacy of curcumin in delaying the development
of T2DM in the pre-diabetes population (Li-Xin et al.,
2013). A total of 240 participants were assigned to receive
either curcumin (1.5 g/day) or placebo capsules, and
changes in β cell functions (homeostasis model assessment
[HOMA]-β, C-peptide, and proinsulin/insulin), insulin
resistance (HOMA-IR), and anti-inammatory cytokine
(adiponectin) levels were recorded at baseline and at three,
six and nine months of treatment. After nine months,
16.4% of participants in the placebo group were diagnosed
with T2DM, whereas none were diagnosed with T2DM in
the curcumin-treated group. Furthermore, participants in
the curcumin-treated group exhibited a better function of
β cells, with higher HOMA-β and lower C-peptide levels.
e curcumin-treated participants also had lower levels
of HOMA-IR and higher adiponectin concentrations,
compared to the placebo group. erefore, curcumin may
be benecial in a pre-diabetes population to delay or prevent
the development of type 2 diabetes mellitus (Li-Xin et al.,
2013).
Although curcumin has shown ecacy against numerous
human diseases, poor bioavailability due to poor absorption,
rapid metabolism, and rapid systemic elimination have
been documented to limit its therapeutic eects (Lin
et al., 2012). e use of adjuvants, which may block the
metabolic pathway of curcumin is the most common
strategy for increasing the bioavailability of curcumin.
e notion of combining piperine, a known inhibitor of
hepatic and intestinal glucuronidation, was evaluated on
the bioavailability of curcumin in healthy human volunteers
(Jianguo et al., 2012). In humans receiving a dose of 2 g
of curcumin alone, serum levels of curcumin were either
undetectable or very low. On the contrary, concomitant
administration of 20 mg of piperine with curcumin,
resulted in much higher concentrations within 30 min
to 1 h after drug treatment; thus, piperine increased the
bioavailability of curcumin by 2,000%. Other promising
TABLE 3. Curcumins eects on renal function parameters. All values are presented as mean ± S.E.M. C-control group, d – diabetic
rats, d + c – diabetic rats treated with curcumin
Study Cur dose
(mg/kg/d)
Plasma
creatinine -
c (mg/dl)
Plasma
creatinine
- d r
Plasma
creatinine
d + c
Ccr - c (ml/
min) Ccr - d Ccr d+c Albuminuria c
(mg / 24 h)
Albuminuria
d
Albuminuria
d+c
Huang,2013 150 0.3 ±
0.06
0.58 ±
0.12
0.36 ±
0.05 14.4 ± 3.56 100 ± 12.87 58.31 ±
14.51
Soetikno,
2013 100 0.3 ±
0.01
2.1 ± 0.1 0.8 ± 0.2 3.9 ± 0.5 0.8 ±
0.2
2.7 ±
0.5
Soetikno,2011 100 0.55 ±
0.02
1.06 ±
0.13
0.69 ±
0.03 3.8 ± 0.9 0.81 ±
0.08
3.61 ±
0.48
Soetikno,
2011 100 0.3 ±
0.01
1.43 ±
0.02
0.36 ±
0.02 3.9 ± 0.7 1.0 ±
0.2
3.0 ±
0.7 13.2 ± 0.6 33.6 ± 5.2 18.8 ± 2.7
Curcumin and diabetes 139
approaches to increase the bioavailability of curcumin
include the use of nanoparticles, liposomes, phospholipid
complexes, and structural analogues (Shoba et al., 1998).
Meriva is a patented phytosome complex of curcumin with
soy phosphatidylcholine that has better bioavailability
than curcumin. e absorption of a curcuminoid mixture
and Meriva was examined in a randomized, double-blind,
human study (Khajehdehi et al., 2012). Total curcuminoid
absorption was about 29-fold higher for the Meriva mixture
than it was for the corresponding unformulated curcuminoid
mixture. Interestingly, the phospholipid formulation
increased the absorption of demethoxylatedcurcuminoids
much more than that of curcumin (Anand et al., 2007).
e bioavailability of curcumin has also been shown to be
greatly enhanced by reconstituting curcumin with the non-
curcuminoid components of turmeric (Te-Yu et al., 2012).
Until now, there are no concerns regarding the safety of
the use of Meriva in human adults (Belcaro et al., 2010).
PERSPECTIVES
Curcumin seems to have a favorable eect in serum
glucose levels, which may be attributed to its ability to inhibit
formation of inammatory cytokines (MCP, IL-6, TNF-α)
either directly or through inhibition of NF-κB and PGE2. In
addition, its benecial eect on inammation is demonstrated
by induction of AMPK and inhibition of MAPK. Studies have
demonstrated a benecial role of curcumin for signicant
diabetic complications, such as diabetic nephropathy,
neuropathy and retinopathy. Further and large-scale studies,
with molecules with better bioavailability, are needed to
conrm its promising potentials in the prevention and
management of diabetes mellitus.
CONFLICTS OF INTEREST STATEMENT
ere is no conict of interest regarding this manuscript.
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142 Curcumin and diabetes
... Diabetes mellitus (DM) is a chronic metabolic disorder characterized by insulin deficiency in Type 1 Diabetes Mellitus (T1DM) and insulin resistance in Type 2 Diabetes Mellitus (T2DM) [Kazazis et al., 2014]. Recently, adipokines have been shown to mediate the critical link between energy balance and insulin resistance [Banerjee et al., 2004]. ...
... Recently, adipokines have been shown to mediate the critical link between energy balance and insulin resistance [Banerjee et al., 2004]. Inflammatory processes, such as obesity, increase the production of pro-inflammatory (leptin, resistin) and anti-inflammatory adipokines (adiponectin), respectively; thus, contributing to the development of diabetes mellitus [Kazazis et al., 2014]. Curcumin, through its antiinflammatory and antioxidant effects, can modulate most of the diabetic complications. ...
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Curcumin, the bioactive component of turmeric, has been used for the treatment of several diseases including diabetes and its complications. Curcumin has been shown to exert pleiotropic effects by modulating different signaling molecules, including transcription factors, chemokines, cytokines, and adipokines. Disturbed regulation of adipokines, which include adiponectin, leptin, resistin, and visfatin, are implicated in the development of insulin resistance and Type 2 Diabetes. Here, we review the findings of in vitro, in vivo, and clinical studies on the modulating effects that curcumin treatment exerts on adipokines. Additionally, we examine the potential beneficial effects of the activity of curcumin in the prevention and treatment of diabetes and its comorbidities.
... Alleged bleeding due to high doses. Both patients have diabetes, then the Curcumin with its anti-diabetic properties is a correct policy provided to the patients [5]. It administered orally every day and chronically. ...
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Curcumin has many advantages, i.e., antioxidant, antiplatelet, anti-inflammatory, and antidiabetic. It was applied for the maturation of arteriovenous fistula (AVF) in the diabetic end-stage renal disease of two diabetic patients. The administration of oral Curcumin examined the maturation on the 4 th week and the 8 th week. The results in both cases show maturity at the end of eight weeks without any complication.
... Physicochemical properties of curcumin get improved in the form of nanoparticles. With the reduction of the particle size and the formation of an amorphous state with the hydrogen bond, it leads to an increase in the release of the compound, reduces the dose of curcumin, and improve its bioavailability (Kazazis et al., 2014). Magnesium (Mg) is an essential intracellular cation and mineral in the living cells of the human body (Rude and Gruber, 2004). ...
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Diabetes results in various complications and 90% of all diabetic cases suffer from type-II diabetes (T2D). Therefore, there is a need to find novel interventions that can protect from diabetic complications and reduce the side effects of currently used antidiabetic drugs. We examined the anti-diabetic effect of Curcumin-Magnesium oxide nanoparticles conjugate (Cur-MgO NPs conj) in streptozotocin (STZ)-induced T2D in male rats while considering hematologic, immunologic, and hepatic metabolic responses. The study included three groups: group 1 (control group), group 2 (STZ-induced T2D), and group 3 (STZ-induced T2D in rats that were orally administered with Cur-MgO NPs conj (5mg/Kg/day for 45 days). Complete blood count, levels of plasma glucose, serum insulin, lipid profile, and hepatic expression of the lipogenic enzymes, namely acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were measured. Histopathological examination of spleen was also conducted. Compared to the control group, a significant elevation in blood glucose and homeostatic model assessment- insulin resistance (HOMA-IR), a substantial reduction in serum insulin level and HOMA-β, an upregulation in hepatic mRNA expression of fatty acid synthase (FAS) and acetyl-CoA carboxylases (ACC), and an altered lipid profile were noticed in STZ-induced T2D group. Oral administration of Cur-MgO NPs conj restored some of the parameters to their physiological levels, including glucose, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c). Histopathological examination of the spleen showed abnormalities in lymphoid cells in T2D, while the treated group showed moderate improvement in spleen tissue, and cells were rescued from apoptosis. The data of this study revealed that Cur-MgO NP conj has a potential ameliorative effect on the hematologic, immunologic, and hepatic metabolic alterations in STZ-induced T2D in rats. © 2020. Shehata et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. All Rights Reserved.
... Curcumin (diferuloylmethane) is the main active constituent of curcuminoid that is used in the traditional medicine overall world (Karfowicz-bodalska, Han, Freier, Smole-ski, & Bodalska, 2017). It has antidiabetic, antioxidant, anti-inflammatory, and anti-cancerous effects based on its crucial biological and pharmacological activities (Kazazis, G. Vallianou, Kollas, & Evangelopoulos, 2014;Meng, Li, & Cao, 2013). Curcumin has been known to reduce hyperglycemia and hyperlipidemia and to improve diabetic problems (Blaslov, 2017). ...
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Objectives This study aimed to assess the immunomodulatory effect of curcumin on innate and adaptive immune responses, as well as its inhibitory power on hyperglycemia in streptozotocin (STZ)-induced diabetic CD1 mice. Material and methods Mice were divided into six groups as follows: normal control mice (I), mice were intraperitoneally (i.p.) injected with either citrate (II), DEMSO (III), or curcumin (170 mg/kg, 3 times/week, for 28 days) (IV), as well as a single intraperitoneal injection of STZ (160 mg/kg) (V) and STZ mice treated with curcumin (VI). The anti-diabetic effect was assessed by estimation of the blood glucose concentration on days 3, 10, 17, 24, and 31. Differential count of white blood cells and the levels of cytokines were also measured at all previous time points. Pancreatic islets were examined for histopathological changes, and the immunohistochemical analysis for insulin and phosphorylated-nuclear factor-kappa B (phospho-NF-κB) was done at the end of the study. Results After curcumin administration, hyperglycemia was improved compared to diabetic mice; however, glucose concentration remains above the normal level. Treatment with curcumin selectively increased the count of lymphocytes and monocytes but decreased the granulocyte count in STZ diabetic mice. Diabetic mice treated with curcumin showed lower levels of interferon (IFN)-γ, interleukin (IL)-6, and IL-1β, as well as a higher level of IL-2 than in diabetic mice. Histopathological alterations that accompanied diabetes induction were ameliorated after curcumin administration. The pancreatic islets of treated diabetic mice displayed a decline in the immunostaining positivity of phospho-NF-κB compared to diabetic mice. Conclusion These results suggest that curcumin has anti-diabetic properties as it can improve the damage caused to the pancreatic β cells by its preferential immunomodulatory action on T helper1-related cytokines, as well as the immunosuppressive activity on proinflammatory cytokines.
... Moreover, it is involved in activating of enzymes in liver, which are associated with glycolysis, gluconeogenic and lipid metabolic process. This creates a normo-glycemic environment to the fetuses preventing defective development [28] . ...
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Background: Diabetes mellitus has a deleterious effect on the offspring including a high tendency for abnormalities and defected immune system. The current study was performed to investigate the effect of maternal diabetes on the development and the innervation of circumvallate tongue papillae in their offspring and the possible beneficial effect of turmeric administration to the diabetic mother in preventing the defective development. Materials and Methods: The study was carried out on 60 pups from diabetic mother rats that were classified into 2 main groups: group I which included untreated diabetic mother rats and group II which included diabetic mother rats treated with 30 mg/kg turmeric by oral gavage. The pups were sacrificed after 3, 10 and 60 days. The circumvallate papillae were dissected and examined histologically, immunohistochemically for S100, histomorphometrically and by quantitative reverse transcriptase-polymerase chain reaction for cytokeratin 8. Results: The histopathological results revealed a deformed outline of the papillae in the untreated rats’ offspring with a decreased number of well-formed taste buds, degenerative effects in Remak’s ganglion and decreased innervation while treated rats’ offspring revealed nearly normal histological structure for the circumvallate papilla and the underlying structures. Immunohistochemical results showed significant differences between untreated and turmeric treated groups in terms of S100 expression. CK8 gene expression results revealed a significant increase in the turmeric treated diabetic subgroups as compared to diabetic untreated subgroups at the same age. Conclusion: Maternal diabetes has a degenerative effect on the taste system of the rat offspring including fewer taste buds with a deformed outline and defective innervation. Treating diabetic mothers with turmeric markedly improved the degenerative effect of diabetes on the offsprings’ circumvallate papillae.
... In addition, lung metastasis of breast cancer cells can be inhibited by curcumin or in mixture with paclitaxel. Endoplasmic reticulum stress and DNA damage can be induced by curcumin resulting in mitochondrialdependent programed cell death (apoptosis) in human cancer A-549 cells via the activation of caspase-3, and enhanced hepatocellular carcinoma apoptosis in HCC J5 cells via increase in intracellular utilization of Ca2+ and the disruption of reactive oxygen species (ROS) in the mitochondria 71,74 . Curcumin is instrumental in preventing cancer invasion and metastasis via inhibition of focal adhesion kinase (FAK) phosphorylation and improving extracellular matrix components expression. ...
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Lead poisoning causes numerous clinical implications in almost all organs, with the brain, liver, and kidneys serving as the primary targets due to the abundant presence of mitochondria. Curcumin is one of the most potent constituents of Curcuma longa, which is lipophilic, phenolic and water insoluble. Curcumin is a strong antioxidant and anti-inflammatory agent in the treatments of neurodegenerative disease, cardiovascular, renal, and liver diseases, with a potential anticancer mechanism in a few clinical and experimental trials. This review will focus on the health impact of lead-induced toxicity in different organ-systems, which occurs as result of increased oxidative stress through the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and will discuss the therapeutic potential of curcumin against lead-induced toxicity in both human and animals.
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Curcumin, used as a spice and traditional medicine in India, exerts beneficial effects against several diseases, owing to its antioxidant, analgesic, and anti-inflammatory properties. Evidence indicates that curcumin might protect against heavy metal-induced organ toxicity by targeting biological pathways involved in anti-oxidation, anti-inflammation, and anti-tumorigenesis. Curcumin has received considerable attention owing to its therapeutic properties, and the mechanisms underlying some of its actions have been recently investigated. Cadmium (Cd) is a heavy metal found in the environment and used extensively in industries. Chronic Cd exposure induces damage to bones, liver, kidneys, lungs, testes, and the immune and cardiovascular systems. Because of its long half-life, exposure to even low Cd levels might be harmful. Cd-induced toxicity involves the overproduction of reactive oxygen species (ROS), resulting in oxidative stress and damage to essential biomolecules. Dietary antioxidants, such as chelating agents, display the potential to reduce Cd accumulation and metal-induced toxicity. Curcumin scavenges ROS and inhibits oxidative damage, thus resulting in many therapeutic properties. This review aims to address the effectiveness of curcumin against Cd-induced organ toxicity and presents evidence supporting the use of curcumin as a protective antioxidant.
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Lead (Pb) is a toxic environmental heavy metal that induces serious clinical defect on all organs with the brain, kidney and liver being the primary targets, hence Pb poisoning has been a major threat to public health in developing countries due to human activities. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with great neuroprotective role as well as being a strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced toxicity in a rat model since the application of chelation therapy is associated with numerous side effects. Thirty-six male Sprague Dawley rats aged 8 weeks weighing between 200 – 250 g were randomly assigned into five (5) groups with 12 rats in Group A (normal saline) and 6 rats each for Group B (LTG) (50 mg/kg of lead acetate for 4 weeks), Group C (RC) (50 mg/kg lead acetate for 4 weeks and left for another 4 weeks without treatment), Group D (Cur100) (50 mg/kg lead acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks) and Group E (Cur200) (50 mg/kg lead acetate, followed by 200 mg/kg curcumin for 4 weeks). All experimental groups received the oral treatment through orogastric-tube on alternate days. Motor functions was assessed using horizontal bar method while Pb concentration in the cerebellum, liver and kidney of the rats were evaluated using inductive coupled plasma mass spectrometry (ICP-MS) techniques. Further, the rats’ cerebellum, liver and kidney were fixed in 10% buffered formalin for 5 days and subsequently prepared for histological examination using paraffin method. The Pb- administered rats showed significant decrease in motor activity scores, SOD activity with increase MDA levels and Pb concentration in their cerebellum, liver, kidney and serum with marked alterations in the histological architecture of the cerebellum, liver and kidney. However, treatment with curcumin improved their functional motor activity, reduced Pb concentration in the cerebellum, liver and kidney and ameliorates the markers of oxidative stress as well as attenuating the alterations in the histological architecture of the cerebellum, liver and kidney. Therefore, it is concluded thatcurcumin attenuates Pb-induced toxicity via inhibition of oxidative stress and chelating activity in rats. Keywords: Curcumin, Lead toxicity, ICP-MS, Horizontal bar, Motor coordination, Oxidative stress, Cerebellum.
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Diabetic Retinopathy (DR) is one of the most common complications of diabetes mellitus that affects the blood vessels of the retina, leading to blindness. The current approach of treatment based on anti-inflammatory, anti-angiogenesis drugs and laser photocoagulation are effective but also shows adverse affect in retinal tissues and that can even worsen the visual abilities. Thus, a safe and effective mode of treatment is needed to control or delaying the DR. Based on the earlier evidence of the potentiality of natural products as anti-oxidants, anti-diabetic and antitumor, medicinal plants may constitute a good therapeutic approach in the prevention of DR. Curcumin, constituents of dietary spice turmeric, has been observed to have therapeutic potential in the inhibition or slow down progression of DR. In this review, we summarize the therapeutic potentiality of curcumin in the delaying the DR through antioxidant, anti-inflammatory, inhibition of Vascular Endothelial Growth and nuclear transcription factors. The strength of involvement of curcumin in the modulation of genes action creates a strong optimism towards novel therapeutic strategy of diabetic retinopathy and important mainstay in the management of diabetes and its complications DR.
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Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a "super curcumin" through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.
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Several studies highlight curcumin's benefit as a hypoglycemic agent, however; a limited number of reports present the importance of curcumin in improvement of pancreatic islets in diabetes. The aim of the present study is to evaluate the antidiabetic effect of a novel curcumin derivative and its effect on pancreatic islet regeneration in type I diabetes-induced by STZ.Materials and methods: Rats were divided into diabetic rats and diabetic rats treated orally with the novel curcumin derivative (NCD) for 40 days. Fasting blood samples were withdrawn periodically from all rats to estimate plasma glucose, insulin and C-peptide for 10 months. Histopathology was performed to allow the assessment of pancreatic islet morphology. Insulin and CD105 were detected immunohistochemically. In diabetic rats, the plasma glucose, insulin and C-peptide levels remained within the diabetic range for about 4 months, after which a gradual decrease in glucose and increase in insulin and C-peptide was observed, which reached almost normal levels after 10 months. NCD treated diabetic rats showed significantly lowered plasma glucose and increased plasma insulin and C-peptide levels. This was followed by a further significant decrease in plasma glucose and increase in plasma insulin and C-peptide after two months from oral administration of the NCD. The plasma insulin and C-peptide continued to increase for ten months reaching levels significantly higher than the basal level. Histopathological examination of diabetic rat pancreas revealed absence of islets of Langerhans, minimal adipose tissue infiltration and localized lymphocytic infiltrates. However, after 6 months of induction of diabetes, rat pancreas showed the appearance of small well formed islets and positive insulin cells but no CD105 positive cells. NCD treated rats showed the appearance of primitive cell collections, large insulin positive cells and CD105 positive cells in the adipose tissue infiltrating the pancreatic tissues. This was followed by the gradual appearance of insulin positive cells in the islets while, CD 105 positive cells remained in the adipose tissue. After 5 and 10 months from the onset of diabetes, rat pancreas showed, well developed larger sized islets with disappearance of primitive cell collections and CD 105 positive cells. Also, insulin positive islets of variable size with disappearance of insulin positive cells in adipose tissue were detected. The NCD possesses antidiabetic actions and enhanced pancreatic islets regeneration.
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Obesity is a state in which there is an over-accumulation of subcutaneous and/or abdominal adipose tissue. This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue produces and releases a variety of adipokines (leptin, adiponectin, resistin, and visfatin), as well as pro- and anti-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-4, IL-6, and others). Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes mellitus or cardiovascular disease. Obesity is thus an underlying condition for inflammatory and metabolic diseases. Diet or dietary patterns play critical roles in obesity and other pathophysiological conditions. A healthy diet and some nutrients are generally considered beneficial; however, some dietary nutrients are still considered controversial. In this article, dietary factors that influence inflammation associated with obesity are discussed.
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Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract.
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Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main enzymes that produce oxidative stress, which plays an important role in painful diabetic neuropathy. Curcumin has been reported to exert an antinociceptive effect in a rat model of diabetic neuropathy by suppressing oxidative stress in the spinal cord. However, it remains unknown whether the mechanism by which curcumin ameliorates diabetic neuropathy can be attributed to spinal NADPH oxidases. This study was designed to determine the effect of curcumin on diabetic neuropathy and to investigate its precise mechanism in relation to NADPH oxidase-mediating oxidative stress in the spinal cord. Diabetic neuropathy was induced in Sprague-Dawley rats by intraperitoneal injection with 1% streptozotocin (STZ; 60mg/kg). After the onset of diabetic neuropathy, a subset of the diabetic rats received daily intragastric administrations of curcumin (200mg/kg) or intraperitoneal injections of apocynin (2.5mg/kg) for 14 consecutive days, whereas other diabetic rats received equivalent volumes of normal saline (NS). STZ resulted in diabetic neuropathy with hyperglycemia and a lower paw withdrawal threshold (PWT), accompanied by elevations in the expression of the NADPH oxidase subunits p47(phox) and gp91(phox) and in the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and a reduction in superoxide dismutase (SOD) activity (P<0.05) in the spinal cord. Both curcumin and apocynin ameliorated diabetic neuropathy. In conclusion, curcumin attenuated neuropathic pain in diabetic rats, at least partly by inhibiting NADPH oxidase-mediating oxidative stress in the spinal cord.
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Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine L-cells. Enhancing GLP-1 action is an important target for prevention and treatment of type 2 diabetes. Several approaches (GLP-1 analogs, dipeptidyl peptidase IV inhibitors) are being used to develop therapeutic agents using GLP-1 action for the treatment of diabetes. However, an alternative approach is to increase endogenous GLP-1 secretion through modulation of the secretory mechanism in intestinal L cells by pharmaceutical agents or dietary ingredients. In the present study, we demonstrate that curcumin, a yellow pigment isolated from the rhizomes of Curcuma longa L, significantly increases GLP-1 secretion in GLUTag cells, and we clarified the structure-activity relationship using curcumin derivatives. Also, concerning the secretory mechanism, the significant increase in GLP-1 secretion by curcumin involved the Ca(2+)-Ca(2+)/calmodulin-dependent kinase II pathway, and was independent of extracellular signal-regulated kinase, PKC, and the cAMP /PKA -related pathway. These findings provide a molecular mechanism for GLP-1 secretion mediated by foods or drugs, and demonstrate a novel biological function of curcumin in regards to GLP-1 secretion.