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
All rights of reproduction in any form reserved
CURCUMIN AND DIABETES: MECHANISMS OF ACTION AND ITS ANTI-DIABETIC
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, Inammation,
Corresponding Author: Natalia G. Vallianou, MD, PhD, 5
Pyramidon str, Municipality of Marathon, 190 05 Athens,
Greece; E-mail: email@example.com
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 suered from the
disease, while this number is expected to rise to 592 million by
year 2035, according to the IDF. Obesity is an inammatory
process that includes, among other things, increased production
of adipokines as well as increased and decreased production
of pro and anti-inammatory 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-
inammatory and possible anti-diabetic eects 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-
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 curcumin’s anti-inammatory,
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 inammation, 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-inammatory molecules, like
adiponectin, and increased production of inammatory ones,
namely leptin, resistin, IL6, MCP-1, TNF-α, PAI-1, Ang II
takes place. Primary mediators for adipose tissue inammation
are toll-like receptors (TLRs) and nuclear factor-κΒ (NF-κB).
e former activates the latter leading to transcription of
inammatory cytokines like IL-6 and TNF-α (Siriwardhana
et al., 2013).
AGEs also play a role in inammation. 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 eects inside the cell
and the extra-cellular matrix. AGE receptors also play a role
in the inammatory process, as they have been identied
on monocytes and macrophages, and their activation leads
to production of inammatory 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 benecial
eect on membrane uidity and transmembrane potential,
resulting in reduction of inammation, by inuencing levels
of lipid peroxidation and MCP-1 release (Lin et al., 2012).
Curcumin inhibits formation of inammatory cytokines
(MCP, IL-6, TNF-α) either directly or through inhibition
of NF-κB and PGE2. Besides, its benecial eect on
inammation 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 identied 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 inammatory cascade, via activation of several
kinases including the c-Jun N-terminal kinase (JNK), leading
to insulin resistance and eventually diabetes (Siriwardhana et
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 signicantly
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
Nanocurcumin (curcumin encapsulated PLGA
nanoparticles) demonstrated a better performace in comparison
with curcumin, as far as delay of cataract development is
concerned, in four dierent 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 opacication and cataract (Cai et al.,
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 inammation (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 eux 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 eux system, and reduction of curcumin’s 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 signicant reduction in
blood glucose levels and weight. Animal studies indicate that
curcumin signicantly 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-inammatory
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
Curcumin’s anti-inammatory eects, besides those
mentioned above, are evident in down-regulation
of 5-hydroxy-eicosatetranoic acid, cyclooxygenase,
lipoxygenase and arachidonic acid metabolism.
Regarding curcumin’s eects 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 curcumin’s inhibitory eect
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
inux 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, benecial for the
kidney, eect was attributed to curcumin’s 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 dierentiation 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-inammatory cytokines, released
from activated microglia in the dorsal horn of the spinal
TABLE 1. Curcumin-induced changes in glucose levels of diabetic rats
measured Control Diabetes Diabetes + Cur
Diabetes + Cur
Diabetes + Cur
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
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 signicant 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
inammation, 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 benecial
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
curcumin’s benecial and statistically signicant eects on
renal function and potential underlying mechanisms (Table
3) (Soetikno et al., 2011b; Huang et al., 2013).
Recently, a randomized, double-blind, clinical trial
assessed the ecacy 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-inammatory 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 benecial in a pre-diabetes population to delay or prevent
the development of type 2 diabetes mellitus (Li-Xin et al.,
Although curcumin has shown ecacy against numerous
human diseases, poor bioavailability due to poor absorption,
rapid metabolism, and rapid systemic elimination have
been documented to limit its therapeutic eects (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. Curcumin’s eects 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
- d r
d + c
Ccr - c (ml/
min) Ccr - d Ccr d+c Albuminuria c
(mg / 24 h)
Huang,2013 150 0.3 ±
0.05 14.4 ± 3.56 100 ± 12.87 58.31 ±
2013 100 0.3 ±
2.1 ± 0.1 0.8 ± 0.2 3.9 ± 0.5 0.8 ±
Soetikno,2011 100 0.55 ±
0.03 3.8 ± 0.9 0.81 ±
2011 100 0.3 ±
0.02 3.9 ± 0.7 1.0 ±
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).
Curcumin seems to have a favorable eect in serum
glucose levels, which may be attributed to its ability to inhibit
formation of inammatory cytokines (MCP, IL-6, TNF-α)
either directly or through inhibition of NF-κB and PGE2. In
addition, its benecial eect on inammation is demonstrated
by induction of AMPK and inhibition of MAPK. Studies have
demonstrated a benecial role of curcumin for signicant
diabetic complications, such as diabetic nephropathy,
neuropathy and retinopathy. Further and large-scale studies,
with molecules with better bioavailability, are needed to
conrm its promising potentials in the prevention and
management of diabetes mellitus.
CONFLICTS OF INTEREST STATEMENT
ere is no conict of interest regarding this manuscript.
Abdel Aziz, M.T., El-Asmar, M.F., Rezg, A.M., Mahfouz, S.M.,
Wassef, M.A., Fouad, H.H., Ahmed, H.H., and Taha, F.M (2013)
e eect of a novel curcumin derivative on pancreatic islet
regeneration in experimental type-1 diabetes in rats. Diabetology
and Metabolic Syndrome 5, 75. doi:10.1186/1758-5996-5-75
Aldebasi, Y., Aly, S.M., and Ahmani, A.Y. (2013) erapeutic
implications of curcumin in the prevention of diabetic
retinopathy via modulation of anti-oxidant activity and
genetic pathways. International Journal of Physiology and
Pathophysiology of Pharmacology 5, 194-202.
Anand, P., Kunnumakkara, A.B., Newman, R.A., Harima,
M., andavarayan, R.A., Veeraveedu, P.T., Arozal, W.,
Sukumaran, V., Lakshmanan, A.P., Arumugam, S., Suzuki,
K., and Aggarwal, B.B. (2007) Bioavailability of curcumin:
problems and promises. Molecular Pharmacology 4, 807-818.
Antony, B., Merina, B., Iyer, V.S., Judy, N., Lennertz, K.,
and Joyal, S. (2008) A pilot cross-over study to evaluate
human oral bioavailability of BCM-95CG (Biocurcumax), a
novel bioenhanced preparation of curcumin. Indian Journal
of Pharmaceutical Science 70, 445-449. doi:10.4103/0250-
TABLE 4. Curcumin’s eects on cardiac function. All values are presented as mean ± S.E.M. C-control group, d – diabetic
rats, d + c – diabetic rats treated with curcumin
Study / echo parameter Aziz, 2013 Yu, 2012 Yu, 2012 Soetikno, 2012
(mg/kg/d) 20 100 200 100
HR cont (beats/min) 166 ± 7 378 ± 11 378 ± 11
HR d 122 ± 5 308 ± 15 308 ± 15
HR d+c 139 ± 6 330 ± 13 364 ± 17
LVDP c 92 ± 5.3
LVDP d 59 ± 6.0
LVDP d+c 70.6 ± 5.3
LV d/dt c 139 ± 7.4
LV d/dt d 101.2 ± 9.4
LV d/dt d+c 134.3 ± 5.2
EF cont (%) 82.4 ± 2.3 82.4 ± 2.3 78.68 ± 2.75
EF d 68.5 ± 5.2 59.68 ± 0.94
EF d+c 76.6 ± 2.9 81.8 ± 2.7 70.35 ± 2.46
Area of brosis c (%) 2.5 ± 0.3
Area of brosis d 6.75 ± 0.75
Area of brosis d+c 3.25 ± 0.25
140 Curcumin and diabetes
Banafshe, H.R., Hamidi, G.A., Noureddini, M., Mirshashemi,
S.M., Mokhtari, R., and Shoferpour, M. (2014) Eect
of curcumin on diabetic peripheral neuropathic pain:
Possible involvement of opioid system. European Journal of
Pharmacology 723, 202-206.
Basnet, P., and Basnet-Skalko, N. (2011) Curcumin: an anti-
inammatory molecule from a curry spice on the path to
cancer treatment. Molecules 16, 4567-4598.
Belcaro, G., Cesarone, M.R., Dugall, M., Pellegrinni, L.,
Ledda, A., Grossi, M.G., Togni, S., and Appendino, G. (2010)
Ecacy and safety of Meriva, a curcumin phosphatidylcholine
complex, during extended administration in osteoarthritis
patients. Alternative Medicine Reviews 15, 337-344.
Cai, K., Qi, D., Hou, X., Wang, O., Chen, J., Deng, B., Qian,
L., Liu, X., and Le, Y. (2011) MCP-1 upregulates amylin
expression in murine pancreatic β cells through ERK/JNK-
AP1 and NF-κB related signaling pathways independent of
CCR2. PLoS ONE 6, e19559.
Chougala, M.B., Jamuna, B.J., Rajan, M.G., and Salimath,
B.V. (2012) Eect of curcumin and quercetin on lysosomal
enzyme activities in streptozotocin-induced diabetic rats.
Clinical Nutrition 31, 749-755.15.
Cuomo, J., Appendino, G., Dern, A.S., Schneider, E.,
McKinnon, T.P., Brown, M.J., Togni, S., and Dixon, B.M.
(2011) Comparative absorption of a standardized curcuminoid
mixture and its lecithin formulation. Journal of Natural
Products 74, 664-669. doi:10.1021/np1007262.
Gota, V.S., Maru, G.B., Soni, T.G., Gandhi, T.R., Kochar,
N., and Agarwal, M.G. (2010) Safety and pharmacokinetics
of a solid lipid curcumin particle formulation in osteosarcoma
patients and healthy volunteers. Journal of Agricultural Food
Chemistry 58, 2095-2099. doi:10.1021/jf9024807.
Goldstein, B.J. (2010) Textbook of Diabetes. Wiley-Blackwell,
4th edition, p.557-559.
Grama, C., Suryanarayana, P., Patil, M., Raghu, G.,
Balakrishna, N., Kumar, M.N., and Reddy, G.B. (2013)
Ecacy of biodegradable curcumin nanoparticles in delaying
cataract in diabetic rat model. PloS ONE 8, e78217.
Hu, T.Y., Liu, C.L., Chuau, C.C., and Hu, M.L. (2012)
Trapping of methylglyoxal by curcumin in cell-free systems
and in human umbilical vein endothelial cells. Journal of
Agricultural Food Chemistry 60, 8190-8196.
Huang, J., Huang, K., Lan, T., Xie, X., Shen, X., Liu, P.,
and Huang, H. (2013) Curcumin ameliorates diabetic
nephropathy by inhibiting the activation of the SphK1-S1P
signaling pathway. Molecular and Cellular Endocrinology 365,
IDF Diabetes Atlas 6th Edition: the global burden: p.1-22.
Joshi, R.P., Negi, P., Kumar, G., Pawar, Y.B., Munjal, B.,
Bensal, A.K., and Sharma, S.S. (2013) SNEDDS curcumin
formulation leads to enhanced protection from pain and
functional decits associated with diabetic neuropathy: an
insight into its mechanism for neuroprotection. Nanomedicine
Khajehdehi, P., Pakfetrat, M., Javidnia, K., Azad, F.,
Malekmakan, L., Nasab, M.H., and Dehghanzadeh, G. (2011)
Oral supple-mentation of turmeric attenuates proteinuria,
transforming growth factor-beta and interleukin-8 levels in
patients with overt type 2 diabetic nephropathy: a randomized,
double-blind and placebo-controlled study. Scandinavian
Journal of Urology and Nephrology 45, 365-70. doi:10.3109/0
Kumar, P.T., Sherin, A., Smijin, S., Kuruvilla, K.P., George,
N., and Paulose, C.S. (2011) Role of curcumin in the
prevention of cholinergic mediated cortical dysfunctions in
streptozotocin-induced diabetic rats. Molecular and Cellular
Endocrinology 331, 1-10.
Lee, H., Lee, I.S., and Choue, R. (2013) Obesity, Inammation
and Diet. Pediatrics Gastroenterology and Hepatology Nutrition
Lin, J., Tang, Y., Kang, Q., and Chen, A. (2012) Curcumin
eliminates the inhibitory eect of advanced glycation end products
(AGEs) on gene expression of AGE receptor-1 in hepatic stellate
cells in vitro. Laboratory Investigation 92, 827-841.
Lin, J., Tang, Y., Kang, Q., Feng, Y., and Chen, A. (2012)
Curcumin inhibits gene expression of receptor for advanced
glycation end- products (RAGE ) in hepatic stellate cells in
vitro by elevating PPAR g activity and attenuating oxidative
stress. British Journal of Pharmacology 166, 2212-2227.
Na, L.X., Li, Y., Pan, H.Z., Zhou, X.L., Sun, D.J., Meng, M.,
Li, X.X., and Sun, C.H. (2013) Curcuminoids exert glucose-
lowering eect in type 2 diabetes by decreasing serum free
fatty acids: a double-blind, placebo-controlled trial. Molecular
Nutrition Food Research 57, 1569-1577.
Margina, D., Gradinaru, D., Manda, G., Neagoe, I., and Ilie,
M. (2013) Membranar eects exerted in vitro by polyphenols:
quercetin, epigallocatechin gallate and curcumin on HUVEC
and Jurkat cells, relevant for diabetes mellitus. Food Chemistry
and Toxicology 61, 86-93.
Patel, P.S., Buras, E.D., and Balasubramanyam, A. (2013) e
Curcumin and diabetes 141
role of the immune system in obesity and insulin resistance.
Journal of Obesity 2013, 616193.
Shehzad, A., Rehman, G., and Lee, Y.S. (2013) Curcumin in
inammatory diseases. Biofactors 39, 69-77.
Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran,
R., and Srinivas, P.S. (1998) Inuence of piperine on the
pharmacokinetics of curcumin in animals and human volunteers.
Planta Medicine 64, 353-356. doi:10.1055/s-2006-957450.
Siriwardhana, N., Kalupahana, N.S., Cekanova, M., Lemieiux,
M., Greer, B., Moustaid-Moussa, N. (2013) Modulation of
adipose tissue inammation by bioactive food compounds.
Journal of Nutrition and Biochemistry 24, 613-623.
Soetikno, V., Sari, V., Sukumaran, F.R., Lakshmanan, A.P.,
Mito, S., Harima, M., andavarayan, R.A., Suzuki, K., Nagata,
M., Takagi, R., and Watanabe, K. (2012) Curcumin prevents
diabetic cardiomyopathy in streptozotocin-induced diabetic
rats: possible involvement of PKC-MAPK signaling pathway.
European Journal of Pharmaceutical Science 47, 604-614.
Soetikno, V., Sari, F.R., Sukumaran, V., Lakshmanan, A.P.,
Harima, M., Suzuki, K., Kawachi, H., and Watanabe, K.
(2013) Curcumin decreases renal triglyceride accumulation
through AMPK-SREBP signaling pathway in streptozotocin-
induced type 1 diabetic rats. Journal of Nutrition and
Biochemistry 24, 796-802.
Soetikno, V., Sari, F.R., Veeraveedu, P.T., andavarayan,
R.A., Harima, M., Sukumaran, V., Lakshmanan, A.P., Suzuki,
K., Kawachi, H., and Watanabe, K. (2011a) Curcumin
ameliorates macrophage inltration by inhibiting NF-κB
activation and proinammatory cytokines in streptozotocin
induced-diabetic nephropathy. Nutrition and Metabolism 8,
Soetikno, V., Watanabe, K., Sari, F.R., Harima, M.,
andavarayan, R.A., Veeraveedu, P.T., Arozal, W., Sukumaran,
V., Lakshmanan, A.P., Arumugam, S., and Suzuki, K. (2011b)
Curcumin attenuates diabetic nephropathy by inhibiting
PKC-α and PKC-β1 activity in streptozotocin-induced type I
diabetic rats. Molecular Nutrition and Food Research 55, 1655-
Sparks, S., Gai, L., Robbins, K.J., and Lazo, N.D. (2012)
Curcumin modulates the self-assembly of the islet amyloid
polypeptide by disassembling α-helix. Biochemistry and
Biophysics Research Communication 422, 551-555.
Takikawa, M., Kurimoto, Y., and Tsuda, T. (2013) Curcumin
stimulated glucagon-like peptide 1secretion in GLUTag cells
via Ca/calmodulin-dependent kinase II activation. Biochemistry
and Biophysics Research Communication 435, 165-170.
Xie, W., and Du, L. (2011) Diabetes is an inammatory
disease: evidence from traditional Chinese medicine. Diabetes
Obesity and Metabolism 13, 289-301.
Yu, W., Wu, J., Cai, F., Xiang, Z., Zha, W., Fan, D., Guo,
S., Ming, Z., and Liu, C. (2012) Curcumin alleviates diabetic
cardiomyopathy in experimental diabetic rats. PloS One 7,
Yue, L., Yong, Z., De-Bao, L., Hai-Ying, L., Wu-Gang H., and
Yu-Shu, D. (2013) Curcumin attenuates diabetic neuropathic
pain by downregulating TNF-α in a rat model. International
Journal of Medical Science 10, 377-381.
Zhang, D., Fu, M., Gao, C.H., and Liu, J.L. (2013)
Curcumin and diabetes: a systematic review. Evidence-Based
Complementary and Alternative Medicine 2013, 636053.
Zhao, W.C., Zhang, B., Liao, M.J., Zhang, W.X., He, W.Y.,
Wang, H.B., and Yang, C.X. (2014) Curcumin ameliorated
diabetic neuropathy partially by inhibition of NADPH oxidase
mediating oxidative stress in the spinal cord. Neuroscience
Letters 560, 81-85.
Zheng, M., Zhang, Q., Joe, Y., Lee, B.H., Ryu Do, G., Kwon,
K.B., Ryter, S.W., and Chung, H.T. (2013) Curcumin induces
apoptotic cell death of activated human CD4+ T cells via
increasing endoplasmic reticulum stress and mitochondrial
dysfunction. International Immunopharmacology 15, 517-523.
142 Curcumin and diabetes