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Therapeutic Potential of Turmeric in Alzheimer's Disease: Curcumin or

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 PHYTOTHERAPY RESEARCH
Phytother. Res. (2013)
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/ptr.5030

REVIEW
Therapeutic Potential of Turmeric in Alzheimer's
Disease: Curcumin or Curcuminoids?

Touqeer Ahmed1 and Anwarul-Hassan Gilani2,3*

1
Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, H-12 Kashmir Highway, Islamabad
44000, Pakistan
2
Natural Products Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College,
Karachi 74800, Pakistan
3
College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia

Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics,
and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and al-
ternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric
possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin,
demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that
curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological
profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constit-
uents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. There-
fore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in
making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medic-
inal value better than curcumin alone. The progress in understanding the disease etiology demands a
multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes
this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.

Keywords: turmeric; curcumin; curcuminoids; synergy; dementia; therapy.

lifespan is prolonged owing to improved health care. Cor-

ALZHEIMER'S DISEASE
Alzheimer's disease (AD) is the most common cause of
dementia originally elucidated by German psychiatrist
Alois Alzheimer (1864–1915) in 1906. Hence, the dis-
ease was named as “Alzheimer's disease,” and this
name was given by Kraepelin (Blennow et al., 2006).
AD is a chronic progressive neurodegenerative disease,
and it accounts for 50–60% of all dementia cases
(Blennow et al., 2006). AD is characterized by clinical
symptoms such as cognitive dysfunction, agitation, de-
pression, delusion, hallucination, insomnia, and wander-
ing (Burns and Iliffe, 2009; Burns et al., 1990; Lahiri
et al., 2002). AD progresses from memory loss to sub-
stantial dementia and death within 8 years of the disease
onset (Avramopoulos, 2009).
It is estimated that half of the people over the age of
85 years are affected with AD (Suh and Checler, 2002),
affecting around 10% of the world population (Vagnucci
and Li, 2003). The prevalence of dementia in the
population below 60–64 years of age is 1%, but this in-
creases exponentially with increasing age, and at the
age of >85 years, the prevalence is 25–33% in the western
population (Blennow et al., 2006; Ferri et al., 2005). AD
represents the sixth leading cause of death, and these fig-
ures are growing at an alarming rate, particularly as the
* Correspondence to: Anwarul-Hassan Gilani, Natural Products Research
Unit, Department of Biological and Biomedical Sciences, The Aga Khan
University Medical College, Karachi-74800, Pakistan.
E-mail: anwar.gilani@aku.edu
Copyright © 2013 John Wiley & Sons, Ltd.
responding data from developing countries are sparse,
but 60% of the AD patients are presumed to live in these
countries (Blennow et al., 2006). Finally, a recent estimate
indicates that there are over 50 million people living with
dementia (Alzheimer's Association Report, 2011). In
terms of its economic impact, the estimated cost of
dementia was $US608bn in 2010, and 70% of this cost
occurred in Western Europe and North America
(Alzheimer's Association Report, 2011). On the basis of
this increasing number of AD cases, there is a need to ex-
plore new therapeutic candidates that offer more effica-
cious, safe, and cost-effective treatment. Drugs having a
potential to delay disease progression are strongly needed
for AD. Medicinal plants can be a rich starting point to
identify new drug candidates for AD, because they have
shown potential in dementia (May et al., 2009).
TURMERIC IN ALZHEIMER'S DISEASE:
BEYOND ITS ROLE AS A CURRY SPICE
Turmeric (a rhizome of Curcuma longa) is a well-known
culinary herb particularly in South Asia, considered as
an essential item in the kitchen and used as a coloring
agent in dietary items (Ammon and Wahl, 1991;
Govindarajan, 1980). Turmeric has a high medicinal
value in the traditional medicine system of South Asia,
which includes aiding in wound healing, inflammatory
conditions, and blood purification (Aggarwal et al., 2007;
Received 3 May 2013
Revised 28 May 2013
Accepted 28 May 2013
 T. AHMED AND A.-H. GILANI
Kapoor, 1990; Krishnaswamy, 2008; Nadkarni, 1976). It
has also been used in asthma, epilepsy, gall stones,
cramps, high cholesterol, congestion, runny nose, cough,
sinusitis, liver disorders, anorexia, rheumatism, diabetic
wounds, and AD (Araujo and Leon, 2001; Duke, 2002;
Gilani et al., 2005). Turmeric also has a long history of
use in traditional Chinese medicines to treat diseases as-
sociated with abdominal pain (Aggarwal et al., 2004).
Turmeric is specifically known for its wound healing and
antiinflammatory properties (Aggarwal et al., 2007;
Krishnaswamy, 2008), which makes it useful in a variety
of diseases, particularly AD and cancers.
Turmeric is a well-studied spice, and multiple studies
have validated its list of medicinal uses, which include be-
ing an antioxidant (Sreejayan and Rao, 1997),
antiinflammatory (Ammon and Wahl, 1991; Brouet and
Ohshima, 1995), anticarcinogenic (Aggarwal and Sung,
2009; Azuine and Bhide, 1992), hepatoprotective (Kiso
et al., 1983), thrombosuppressive (Srivastava et al., 1985),
cardioprotective and anti-ischemic (Dikshit et al., 1995;
Nirmala and Puvanakrishnan, 1996; Venkatesan, 1998), va-
sodilator (Gilani et al., 2005), antispasmodic and broncho-
dilator (Gilani et al., 2005), antidepressant (Yu et al.,
2002), neuroprotective (Rajakrishnan et al., 1999), hypo-
glycemic (Arun and Nalini, 2002; Babu and Srinivasan,
1995; Srinivasan, 1972), and anti-arthritic (Deodhar et al.,
1980) and being effective in AD (Shytle et al., 2012). These
listed studies indicate that turmeric has immense potential
in multiple pathological states.
Furthermore, what is even more fascinating about
turmeric is that it is very safe even when used in large
amounts, according to the studies conducted in animal
(Qureshi et al., 1992; Shankar et al., 1980) and human
subjects (Lao et al., 2006). Although there is limited
supportive scientific evidence; the lower prevalence of
AD in India is generally attributed to the turmeric con-
sumption as a part of curry, and it is assumed that people
who use turmeric regularly have a lower incidence of
AD (Ganguli et al., 2000). A study by Ng et al. was
conducted to show such association, and it was found
that elderly people who frequently consume curry have
better cognitive performance, but additional studies are
required to strengthen the scientific evidence for this
finding (Ng et al., 2006).
CHEMICAL CONSTITUENTS OF TURMERIC IN
RELATION TO ALZHEIMER'S DISEASE:
CURCUMIN OR CURCUMINOIDS?
There is a long list of compounds that have been
isolated from turmeric and studied. These include
curcumin, bisdemethoxycurcumin, demethoxycurcumin,
eugenol, dihydrocurcumin, azulene, borneol, D-camphene,
caprylic acid, cineol, turmerone, and zingiberine
(Duke, 1992). It is also reported to contain β-caryophyllene,
β-bisabolene, and β-sesquiphellandrenendrene (Qin et al.,
2007). Studies on various components of turmeric, such as
curcumin, bisdemethoxycurcumin, and demethoxycurcumin
(Fig. 1), have provided insights that support turmeric's
medicinal use in AD. These three compounds are found
in turmeric in a specific ratio (3–5% bisdemethoxycurcumin,
15–20% demethoxycurcumin, and 75–80% curcumin), and
this combination is called curcuminoids or the curcuminoid
Copyright © 2013 John Wiley & Sons, Ltd.
Figure 1. Chemical structure of curcumin (A), demethoxycurcumin
(B), and bisdemethoxycurcumin (C).
mixture (Ahmed and Gilani, 2009), which is known as a vital
ingredient of turmeric (Aggarwal et al., 2007).
There are two types of studies found in the literature
regarding the purity of curcuminoids. In the first case,
scientists use the name of curcumin and curcuminoid
mixture (also known as commercial curcumin) inter-
changeably. In the second case, curcumin is used as a
single chemical. Some studies even use the word “curry
spice” for turmeric and curcumin. We feel that it is im-
portant to highlight curcumin and curcuminoids as sepa-
rate entities in terms of their pharmacological profile,
particularly in AD (Ahmed and Gilani, 2009; Ahmed
et al., 2011).
PHARMACODYNAMIC PROPERTIES OF THE
CURCUMINOID MIXTURE AND ITS
INDIVIDUAL CONSTITUENTS
The curcuminoid mixture shows an array of activities
that can be helpful in ameliorating AD symptoms acting
on various target sites (Dohare et al., 2008; Lin et al.,
2008; Sreejayan and Rao, 1994). Curcuminoids are
known to clear Aβ by promoting its uptake in cell cul-
ture systems (Zhang et al., 2006), and the mode of
phagocytic activity is reported to be noninflammatory,
suggestive of their potential in neurodegenerative dis-
eases (Bisht et al., 2009). Curcuminoids not only inhibit
Aβ fibril formation (Kim et al., 2005) but also prevent
the cellular insult induced by the Aβ peptide (Kim
et al., 2001). These studies indicate that curcuminoids
probably interfere with the formation of plaques and
reduce their toxic nature, but the exact mechanism
remains to be elucidated.
There is a list of studies elaborated in Table 1 that dem-
onstrate the neuroprotective potential of curcuminoids in
various models, which highlights that curcuminoids act as
a mixture through multiple mechanisms in AD. However,
the contribution of the individual components needs fur-
ther investigation. On the basis of the data from our and
other laboratories, potential targets of curcuminoids in
AD are illustrated in Fig. 2.
Curcuminoids are a mixture of three compounds
(curcumin, bisdemethoxycurcumin, and demethoxycurcumin);
therefore, studying the contribution of each component in
the curcuminoid mixture will further help us better under-
stand their pharmacological profile. Already some of the
Phytother. Res. (2013)
 THERAPEUTIC POTENTIAL OF TURMERIC IN AD

Table 1. Studies on curcuminoids showing neuroprotective effect in different models:

studies have demonstrated a distinct effect of each com-
ponent of the curcuminoid mixture (Table 2).
As shown in Table 2, all three compounds have variable
efficacy or potency in different models, with no clear su-
premacy of curcumin over the other two compounds or
Copyright © 2013 John Wiley & Sons, Ltd.
the mixture. In fact, the parent mixture has not been
widely studied as such to compare its efficacy with that
of individual compounds. Sandur et al. (2007) showed
the mixture as being more effective than curcumin or
other the two individual compounds in TNF-induced
Phytother. Res. (2013)
 T. AHMED AND A.-H. GILANI
Figure 2. Therapeutic targets of curcuminoids in Alzheimer's dis-
ease. This diagram shows therapeutic targets of curcuminoids at
various levels with appropriate citations in the square brackets.
(1) Decrease in formation of neurotoxic Aβ from the amyloid pre-
cursor protein (Zhang et al., 2010a). (2) Rescue of Aβ-induced syn-
aptic impairments and improvement of memory (Ahmed et al.,
2010, 2011). (3) Decrease in inflammatory stress and improve-
ment in neuronal survival by inhibiting cell death (Ahmed and
Gilani, 2011). (4) Inhibition of nuclear factor κB (NF-κB) and attenua-
tion of stress-inducing cytokines (Sandur et al., 2007; Zhang et al.,
2010b). (5) Improvement in neuronal survival by inhibiting cell death
(Kim et al., 2001). (6) Reduction in tau hyperphosphorylation and
resulting decrease in neurofibrillary tangles (Ma et al., 2009; Park
et al., 2008). (7) Attenuation of muscarinic insufficiency by inhibiting
acetylcholinesterase enzyme, resulting in increased cognitive func-
tion (Ahmed and Gilani, 2009). This figure is available in colour online
at wileyonlinelibrary.com/journal/ptr
nuclear factor κB suppression. Similarly, studies
conducted in our laboratory on the curcuminoid mixture
and its comparison with individual compounds clearly
Table 2. Showing list of studies, where curcuminoids are compared for different activities:
Copyright © 2013 John Wiley & Sons, Ltd.
showed that curcumin was not the most effective in all
models of AD, whereas in some cases, the parent mixture
was more effective or as effective as some of the individ-
ual compounds (Ahmed and Gilani, 2009; Ahmed et al.,
2010, 2011). Therefore, the need to conduct detailed com-
parative studies of the curcuminoid mixture and its indi-
vidual compounds in different models to assess and
analyze their bioavailability and therapeutic potential
arises.
Various in vivo studies provided supporting evidence
and highlighted the therapeutic potential of curcumin in
AD. Administration of curcumin to an AD mouse model
resulted in a decreased serum Aβ level as well as reduced
Aβ burden in the brain, and this effect was prominently
shown in the neocortex and hippocampus of the AD
mouse model (Wang et al., 2009). Curcumin crosses the
blood–brain barrier and inhibits Aβ fibril formation and
is capable of inducing disaggregation of preformed Aβ
fibrils and their extension (Garcia-Alloza et al., 2007;
Ono et al., 2004; Yang et al., 2005). Curcumin inhibited
Aβ fibril formation more efficiently than naproxen or ibu-
profen (Yang et al., 2005). Curcumin treatment rescued
the distorted neuritic morphology present near plaques,
thereby providing a useful therapeutic effect in AD
(Garcia-Alloza et al., 2007). Production and maturation
of amyloid precursor protein (APP) is another pathway
disrupted in AD (Suh and Checler, 2002). Curcumin was
found to reduce the production of Aβ with a simultaneous
decrease in presenilin 1 gene expression, suggesting its
role in γ-secretase modulation (Xiong et al., 2011). More-
over, it is also possible that the decreased production of
APP is due to the effect of curcumin on attenuating
APP maturation (Zhang et al., 2010a). Further studies
are required to elaborate the detailed mechanism of
curcumin and other components of curcuminoid mixture.
Curcumin is one of the most extensively studied com-
pounds, and it is generally believed that curcumin is the
compound responsible for the therapeutic success of
turmeric in a wide range of disorders. However, a large
group of pharmacologists believe in the philosophy that
no single compound can be a true representative of a
plant (Gilani & Atta-ur-Rahman, 2005), as the single
Phytother. Res. (2013)
 THERAPEUTIC POTENTIAL OF TURMERIC IN AD
plant can contain as many as thousands of chemicals.
Hence, we also studied the other two compounds of the
curcuminoid mixture, and we demonstrated that
bisdemethoxycurcumin was the most potent component
of the curcuminoid mixture, when studied in the in vitro
acetylcholinesterase enzyme inhibition assay (Ahmed
and Gilani, 2009). On the other hand, the curcuminoid
mixture was found more effective in the in vivo system
in inhibiting the acetylcholinesterase enzyme in the hip-
pocampal area (Ahmed and Gilani, 2009). In a rat
model of AD, curcumin was found to be more effective
compared with the parent curcuminoid mixture or the
other individual compounds (bisdemethoxycurcumin
and demethoxycurcumin) for its effect on memory when
evaluated in the Morris water maze test (Ahmed et al.,
2010). Furthermore, these findings were supported by
the rescuing effect of curcumin on long-term potentiation
in the presence of Aβ peptide application (Ahmed et al.,
2011). In the same model, demethoxycurcumin was found
to be more effective for its effect on the calcium/calmodu-
lin-dependent protein kinase type IV expression, showing
that each component contributed distinctly (Ahmed et al.,
2010). When the curcuminoid mixture and its indivi-
dual components were studied for their effect on
antiinflammatory gene expression, bisdemethoxycurcumin
and demethoxycurcumin decreased glial fibrillary acidic
protein levels more efficiently than did curcumin,
whereas only demethoxycurcumin decreased the levels
of inflammatory cytokine interleukin-1β, suggesting
antiinflammatory properties of these constituents
(Ahmed and Gilani, 2011) and showing their distinct effects.
Medicinal plants that are known to contain multiple
constituents are considered to possess an “effect en-
hancing and/or side-effect neutralizing combination of
activities” (Gilani & Atta-ur-Rahman, 2005). This also
appears to be true for the turmeric/curcuminoid mix-
ture, and from the studies described earlier, it is con-
cluded that each compound of the curcuminoid
mixture plays a distinct, important role towards the con-
tribution of the pharmacological profile of curcuminoid
mixture or turmeric in AD. This makes it clear that it
is not only curcumin but also the other constituents in
the curcuminoid mixture that are equally important,
rendering the curcuminoid mixture as the true represen-
tative of turmeric, rather than curcumin alone. Further
studies are required to elaborate the detailed mecha-
nism of curcumin and other components of the
curcuminoid mixture.
PHARMACOKINETIC PROPERTIES OF
CURCUMINOIDS
Curcuminoids have limited bioavailability when taken
orally, although this can be overcome if proper mea-
sures are taken. Studies at different levels have long
been conducted to understand the pharmacokinetics of
these compounds (Wahlstrom and Blennow, 1978).
When curcuminoids are taken orally, their bioavailabil-
ity is low (Wahlstrom and Blennow, 1978). There are
very few studies measuring the bioavailability of the
individual compounds other than the curcuminoid
mixture; however, in reality, these compounds are
detectable in plasma when high doses are administered
Copyright © 2013 John Wiley & Sons, Ltd.
(Cheng et al., 2001; Dhillon et al., 2008; Lao et al.,
2006). Various studies have shown that following admin-
istration of curcumin, brain levels were found to be in
the range of 400–900 ng/g of brain tissue (Ireson et al.,
2001; Pan et al., 1999; Perkins et al., 2002), suggesting
the ability of curcumin to cross the blood–brain barrier.
Recently, scientists have been trying to find a vehicle
medium for the administration of the curcuminoids.
The solubility of the curcuminoids in various aqueous
media has not shown promising results, which adds an-
other limitation along with being less bioavailable. Inter-
estingly, recent data show that bisdemethoxycurcumin
is the most stable component when prepared in
serum media (Quitschke, 2008). The order of the
stability is reported to be bisdemethoxycurcumin >
demethoxycurcumin > curcumin, and these compounds
are stable over days in this medium under different condi-
tions (Quitschke, 2008). Hence, bisdemethoxycurcumin is
present in the lowest amount but stable for the longest
time, which makes bisdemethoxycurcumin an equally
vital constituent of the curcuminoid mixture, which in-
cludes demethoxycurcumin and curcumin. Further stud-
ies are required to investigate the combined effects of
curcuminoids on stability.
WAYS TO IMPROVE BIOAVAILABILITY OF
CURCUMINOIDS
There are several ways to improve the bioavailability of
curcumin, such as heating (Kurien and Scofield, 2009)
or combining with piperine, which is an active principal
of black pepper (Shoba et al., 1998). A study conducted
on animals and humans showed that co-administration
of piperine, which blocks hepatic and intestinal
glucuronidation, enhanced curcumin bioavailability by
preventing its metabolism (Shoba et al., 1998). Solubili-
zation of curcumin in turmeric oil also increases
bioavailability in rats and humans (Antony et al.,
2008). Because curcumin is able to cross the blood–
brain barrier (Begum et al., 2008; Pan et al., 1999;
Perkins et al., 2002), newer ways to improve its solubility
will increase its bioavailability and further augment
brain penetration. Intestinal permeation of curcumin is
more efficient in its natural form (from turmeric) than
in its isolated chemical form (Shishu and Maheshwari,
2010). Thus, it is reasonable to speculate that the bio-
availability of individual compounds, in particular
curcumin, will be enhanced if taken in the natural form
as compared with when taken alone. Further studies in
this direction will provide useful information about the
pharmacokinetics of curcuminoids.
METABOLITES OF CURCUMINOIDS AND
THEIR POTENTIAL IN ALZHEIMER'S DISEASE
It is interesting to know that curcumin and a few of its
metabolites have shown therapeutic potential for AD
(Begum et al., 2008; Mishra et al., 2011). Curcumin is pri-
marily metabolized to reductive metabolites (Hoehle
et al., 2006), and most of these metabolites and parent
compounds are subject to conjugation (Holder et al.,
Phytother. Res. (2013)
 T. AHMED AND A.-H. GILANI
1978; Ireson et al., 2001). Commonly known reductive
metabolites of curcumin are tetrahydrocurcumin,
hexahydrocurcumin, and octahydrocurcumin (Begum
et al., 2008; Hoehle et al., 2006). On the other hand,
metabolic products of bisdemethoxycurcumin and
demethoxycurcumin are less studied than those of
curcumin.
Comparison of tetrahydrocurcumin and curcumin
showed that only curcumin was effective in reducing
plaque burden (Begum et al., 2008). A recent study has
reported that tetrahydrocurcumin showed protection par-
ticularly against Aβ-oligomer-induced toxicity, which was
attributed to its antioxidant activity (Mishra et al., 2011).
Under in vivo conditions, tetrahydrocurcumin was shown
to reduce the neuroinflammation but ineffective in reduc-
ing plaques and insoluble Aβ (Begum et al., 2008).
Ferulic acid is another metabolite of the curcumin
(Begum et al., 2008) that is known to possess antioxidant
(Graf, 1992; Scott et al., 1993) and antiinflammatory ac-
tivities (Fernandez et al., 1998; Ozaki, 1992). Ferulic acid
inhibited fibril Aβ formation and extension from amy-
loid beta-peptide in a dose-dependent manner (Ono
et al., 2005). When tested under the in vivo conditions
in a transgenic AD mouse model (Tg2576), ferulic acid
did not show a therapeutically significant effect on the
amyloid profile (Hamaguchi et al., 2009), which is pre-
sumably due to the fact that ferulic acid has poor brain
penetration (Begum et al., 2008).
Little is known about the metabolic products of the
demethoxycurcumin (Zeng et al., 2007); therefore,
pharmacological studies of these metabolites to eluci-
date their role in AD would generate promising
knowledge in this field. It is known that curcumin and
demethoxycurcumin are chemically less stable as com-
pared with bisdemethoxycurcumin (Hoehle et al.,
2006); therefore, if we can identify metabolites that
can therapeutically support parent curcuminoids in
AD, this would augment the value of curcuminoids.
LIMITATIONS ASSOCIATED WITH
CURCUMINOIDS
Turmeric and curcuminoids are relatively safe in human
beings, even when administered in high doses (Lao
et al., 2006). Although limited side effects are reported
for the curcuminoids, curcumin is known to cause contact
REFERENCES
Alzheimer's Association Report. 2011.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H. 2007.
Curcumin: the Indian solid gold. Adv Exp Med Biol 595: 1–75.
Aggarwal BB, Sung B. 2009. Pharmacological basis for the role of
curcumin in chronic diseases: an age-old spice with modern
targets. Trends Pharmacol Sci 30: 85–94.
Aggarwal BB, Takada Y, Oommen OV. 2004. From chemopreven-
tion to chemotherapy: common targets and common goals.
Expert Opin Investig Drugs 13: 1327–1338.
Ahmed T, Enam SA, Gilani AH. 2010. Curcuminoids enhance
memory in an amyloid-infused rat model of Alzheimer's dis-
ease. Neuroscience 169: 1296–1306.
Ahmed T, Gilani AH. 2009. Inhibitory effect of curcuminoids on
acetylcholinesterase activity and attenuation of scopolamine-
induced amnesia may explain medicinal use of turmeric in
Alzheimer's disease. Pharmacol Biochem Behav 91: 554–559.
Copyright © 2013 John Wiley & Sons, Ltd.
dermatitis (Liddle et al., 2006) and is contraindicated in
patients with biliary tract obstruction, because of its
ability to induce gall bladder contraction (Rasyid and
Lelo, 1999; Rasyid et al., 2002). Curcumin has been taken
into clinical trials for various ailments, but clinical trials
with reference to AD have not shown noteworthy thera-
peutic potential. Two studies are important to highlight,
where curcumin was administered for a 6-month duration
in AD patients, but no significant improvement was
observed (Baum et al., 2008; Ringman et al., 2008). There-
fore, further clinical studies using curcuminoid mixture
may produce a meaningful outcome.
CONCLUSION
A literature search revealed that curcuminoid mixture
and its individual components show variation in their
effects in different pharmacological activities (Table 1).
Moreover, from the studies summarized in Table 2, it
is evident that the different constituents of the
curcuminoid mixture show different biological activities
with different efficacy and potency. Especially, there are
some studies (Table 2) where curcumin was less effec-
tive as compared with the other two compounds or par-
ent curcuminoid mixture. Hence, this review provides
evidence that curcuminoids, being a mixture of three
compounds (acting through multiple pathways), shows
cumulative or synergistic properties of its individual
constituents and each constituent in the parent mixture
plays an important role by either acting through distinct
pathway(s) or being stable for a longer time. Therefore,
the curcuminoid mixture offers better therapeutic
potential in AD as compared with pure curcumin and
offers promising therapeutic potential in AD.
Acknowledgements
We thank Dr. Graeme Cane, past Head, Center of English Language,
for language correction.
Conflict of Interest
All authors declare no conflict of interest.
Ahmed T, Gilani AH. 2011. A comparative study of curcuminoids
to measure their effect on inflammatory and apoptotic gene
expression in an A beta plus ibotenic acid-infused rat model
of Alzheimer's disease. Brain Res 1400: 1–18.
Ahmed T, Gilani AH, Hosseinmardi N, Semnanian S, Enam SA,
Fathollahi Y. 2011. Curcuminoids rescue long-term potentia-
tion impaired by amyloid peptide in rat hippocampal slices.
Synapse 65: 572–582.
Ammon HP, Wahl MA. 1991. Pharmacology of Curcuma longa.
Planta Med 57: 1–7.
Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. 2008. A
pilot cross-over study to evaluate human oral bioavailability of
BCM-95CG (biocurcumax), a novel bioenhanced preparation
of curcumin. Indian J Pharm Sci 70: 445–449.
Araujo CC, Leon LL. 2001. Biological activities of Curcuma longa
L. Mem Inst Oswaldo Cruz 96: 723–728.
Phytother. Res. (2013)
 THERAPEUTIC POTENTIAL OF TURMERIC IN AD
Arun N, Nalini N. 2002. Efficacy of turmeric on blood sugar and
polyol pathway in diabetic albino rats. Plant Foods Hum Nutr
57: 41–52.
Avramopoulos D. 2009. Genetics of Alzheimer's disease: recent
advances. Genome Med 1: 34.
Azuine MA, Bhide SV. 1992. Chemopreventive effect of turmeric
against stomach and skin tumors induced by chemical carcin-
ogens in Swiss mice. Nutr Cancer 17: 77–83.
Babu PS, Srinivasan K. 1995. Influence of dietary curcumin and
cholesterol on the progression of experimentally induced dia-
betes in albino rat. Mol Cell Biochem 152: 13–21.
Bala K, Tripathy BC, Sharma D. 2006. Neuroprotective and anti-
ageing effects of curcumin in aged rat brain regions.
Biogerontology 7: 81–89.
Baum L, Lam CW, Cheung SK, et al. 2008. Six-month randomized,
placebo-controlled, double-blind, pilot clinical trial of curcumin
in patients with Alzheimer disease. J Clin Psychopharmacol
28: 110–113.
Begum AN, Jones MR, Lim GP, et al. 2008. Curcumin structure–
function, bioavailability, and efficacy in models of
neuroinflammation and Alzheimer's disease. J Pharmacol Exp
Ther 326: 196–208.
Bhutani MK, Bishnoi M, Kulkarni SK. 2009. Anti-depressant like ef-
fect of curcumin and its combination with piperine in
unpredictable chronic stress-induced behavioral, biochemical
and neurochemical changes. Pharmacol Biochem Behav 92:
39–43.
Bisht K, Choi WH, Park SY, Chung MK, Koh WS. 2009. Curcumin
enhances non-inflammatory phagocytic activity of RAW264.7
cells. Biochem Biophys Res Commun 379: 632–636.
Blennow K, de Leon MJ, Zetterberg H. 2006. Alzheimer's disease.
Lancet 368: 387–403.
Brouet I, Ohshima H. 1995. Curcumin, an anti-tumour promoter
and anti-inflammatory agent, inhibits induction of nitric oxide
synthase in activated macrophages. Biochem Biophys Res
Commun 206: 533–540.
Burns A, Iliffe S. 2009. Alzheimer's disease. BMJ 338: b158.
Burns A, Jacoby R, Levy R. 1990. Psychiatric phenomena in
Alzheimer's disease. IV: disorders of behaviour. Br J Psychia-
try 157: 86–94.
Cheng AL, Hsu CH, Lin JK, et al. 2001. Phase I clinical trial of
curcumin, a chemopreventive agent, in patients with high-
risk or pre-malignant lesions. Anticancer Res 21: 2895–2900.
Dairam A, Limson JL, Watkins GM, Antunes E, Daya S. 2007.
Curcuminoids, curcumin, and demethoxycurcumin reduce
lead-induced memory deficits in male Wistar rats. J Agric Food
Chem 55: 1039–1044.
Deodhar SD, Sethi R, Srimal RC. 1980. Preliminary study on anti-
rheumatic activity of curcumin (diferuloyl methane). Ind J
Med Res 71: 632–634.
Dhillon N, Aggarwal BB, Newman RA, et al. 2008. Phase II trial of
curcumin in patients with advanced pancreatic cancer. Clin
Cancer Res 14: 4491–4499.
Dikshit M, Rastogi L, Shukla R, Srimal RC. 1995. Prevention of
ischaemia-induced biochemical changes by curcumin & quini-
dine in the cat heart. Ind J Med Res 101: 31–35.
Dohare P, Garg P, Jain V, Nath C, Ray M. 2008. Dose dependence
and therapeutic window for the neuroprotective effects of
curcumin in thromboembolic model of rat. Behav Brain Res
193: 289–297.
Duke JA. 1992. Handbook of Phytochemical Constituents of
GRAS Herbs and Other Economic Plants. CRC Pres: Boca
Raton, Florida.
Duke JA. 2002. Hand Book of Medicinal Herbs. CRC Press. Boca
Raton, Florida.
El-Demerdash FM, Yousef MI, Radwan FM. 2009. Ameliorating ef-
fect of curcumin on sodium arsenite-induced oxidative dam-
age and lipid peroxidation in different rat organs. Food Chem
Toxicol 47: 249–254.
Fernandez MA, Saenz MT, Garcia MD. 1998. Anti-inflammatory
activity in rats and mice of phenolic acids isolated from
Scrophularia frutescens. J Pharm Pharmacol 50: 1183–1186.
Ferri CP, Prince M, Brayne C, et al. 2005. Global prevalence of de-
mentia: a Delphi consensus study. Lancet 366: 2112–2117.
Frautschy SA, Hu W, Kim P, et al. 2001. Phenolic anti-
inflammatory antioxidant reversal of A beta-induced cognitive
deficits and neuropathology. Neurobiol Aging 22: 993–1005.
Ganguli M, Chandra V, Kamboh MI, et al. 2000. Apolipoprotein E
polymorphism and Alzheimer disease: the Indo-US Cross-
National Dementia Study. Arch Neurol 57: 824–830.
Copyright © 2013 John Wiley & Sons, Ltd.
Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ.
2007. Curcumin labels amyloid pathology in vivo, disrupts
existing plaques, and partially restores distorted neurites in
an Alzheimer mouse model. J Neurochem 102: 1095–1104.
Gilani AH, Atta-ur-Rahman. 2005. Trends in ethnopharmacology. J
Ethnopharmacol 100: 43–49.
Gilani AH, Shah AJ, Ghayur MN, Majeed K. 2005. Pharmacological
basis for the use of turmeric in gastrointestinal and respiratory
disorders. Life Sci 76: 3089–3105.
Govindarajan VS. 1980. Turmeric—chemistry, technology, and
quality. Crit Rev Food Sci Nutr 12: 199–301.
Graf E. 1992. Antioxidant potential of ferulic acid. Free Radic Biol
Med 13: 435–448.
Hamaguchi T, Ono K, Murase A, Yamada M. 2009. Phenolic com-
pounds prevent Alzheimer's pathology through different ef-
fects on the amyloid-beta aggregation pathway. Am J Pathol
175: 2557–2565.
Hoehle SI, Pfeiffer E, Solyom AM, Metzler M. 2006. Metabolism of
curcuminoids in tissue slices and subcellular fractions from rat
liver. J Agric Food Chem 54: 756–764.
Holder GM, Plummer JL, Ryan AJ. 1978. The metabolism and excre-
tion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,
6-heptadiene-3,5-dione) in the rat. Xenobiotica 8: 761–768.
Ireson C, Orr S, Jones DJ, et al. 2001. Characterization of metab-
olites of the chemopreventive agent curcumin in human and
rat hepatocytes and in the rat in vivo, and evaluation of their
ability to inhibit phorbol ester-induced prostaglandin E2 pro-
duction. Cancer Res 61: 1058–1064.
Ishrat T, Hoda MN, Khan MB, et al. 2009. Amelioration of cognitive
deficits and neurodegeneration by curcumin in rat model of
sporadic dementia of Alzheimer's type (SDAT). Eur
Neuropsychopharmacol 9: 636–647
Isik AT, Celik T, Ulusoy G, et al. 2009. Curcumin ameliorates im-
paired insulin/IGF signalling and memory deficit in a
streptozotocin-treated rat model. Age (Dordr) 31: 39–49.
Kapoor L. 1990. Handbook of Ayurvedic Medicinal Plants. CRC
Press: Boca Raton, Florida.
Kim DS, Park SY, Kim JK. 2001. Curcuminoids from Curcuma
longa L. (Zingiberaceae) that protect PC12 rat pheochromocy-
toma and normal human umbilical vein endothelial cells from
beta A(1–42) insult. Neurosci Lett 303: 57–61.
Kim H, Park BS, Lee KG, et al. 2005. Effects of naturally occurring
compounds on fibril formation and oxidative stress of beta-
amyloid. J Agric Food Chem 53: 8537–8541.
Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H. 1983.
Antihepatotoxic principles of Curcuma longa rhizomes. Planta
Med 49: 185–187.
Krishnaswamy K. 2008. Traditional Indian spices and their health
significance. Asia Pac J Clin Nutr 17 Suppl 1: 265–268.
Kulkarni SK, Bhutani MK, Bishnoi M. 2008. Antidepressant activity
of curcumin: involvement of serotonin and dopamine system.
Psychopharmacology (Berl) 201: 435–442.
Kumar P, Padi SS, Naidu PS, Kumar A. 2007. Possible
neuroprotective mechanisms of curcumin in attenuating 3-
nitropropionic acid-induced neurotoxicity. Methods Find Exp
Clin Pharmacol 29: 19–25.
Kurien BT, Scofield RH. 2009. Increasing aqueous solubility of
curcumin for improving bioavailability. Trends Pharmacol Sci
30: 334–335; author reply 335.
Lahiri DK, Farlow MR, Greig NH, Sambamurti K. 2002. Current
drug targets for Alzheimer's disease treatment. Drug Dev
Res 56: 267–281.
Lao CD, Ruffin MTt, Normolle D, et al. 2006. Dose escalation of a
curcuminoid formulation. BMC Complement Altern Med 6: 10.
Li YC, Wang FM, Pan Y, et al. 2009. Antidepressant-like effects of
curcumin on serotonergic receptor-coupled AC-cAMP path-
way in chronic unpredictable mild stress of rats. Prog
Neuropsychopharmacol Biol Psychiatry 33: 435–449.
Liddle M, Hull C, Liu C, Powell D. 2006. Contact urticaria from
curcumin. Dermatitis 17: 196–197.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. 2001.
The curry spice curcumin reduces oxidative damage and amy-
loid pathology in an Alzheimer transgenic mouse. J Neurosci
21: 8370–8377.
Lin R, Chen X, Li W, Han Y, Liu P, Pi R. 2008. Exposure to metal
ions regulates mRNA levels of APP and BACE1 in PC12 cells:
blockage by curcumin. Neurosci Lett 440: 344–347.
Ma QL, Yang F, Rosario ER, et al. 2009. Beta-amyloid oligomers
induce phosphorylation of tau and inactivation of insulin
receptor substrate via c-Jun N-terminal kinase signaling:
Phytother. Res. (2013)
 T. AHMED AND A.-H. GILANI
suppression by omega-3 fatty acids and curcumin. J Neurosci
29: 9078–9089.
May BH, Lit M, Xue CC, et al. 2009. Herbal medicine for dementia:
a systematic review. Phytother Res 23: 447–459.
Mishra S, Mishra M, Seth P, Sharma SK. 2011.
Tetrahydrocurcumin confers protection against amyloid beta-
induced toxicity. Neuroreport 22: 23–27.
Nadkarni KM. 1976. Indian Materia Medica. Popular Prakashan:
Bombay.
Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. 2006. Curry con-
sumption and cognitive function in the elderly. Am J Epidemiol
164: 898–906.
Nirmala C, Puvanakrishnan R. 1996. Protective role of curcumin
against isoproterenol induced myocardial infarction in rats.
Mol Cell Biochem 159: 85–93.
Ono K, Hasegawa K, Naiki H, Yamada M. 2004. Curcumin has po-
tent anti-amyloidogenic effects for Alzheimer's beta-amyloid
fibrils in vitro. J Neurosci Res 75: 742–750.
Ono K, Hirohata M, Yamada M. 2005. Ferulic acid destabilizes
preformed beta-amyloid fibrils in vitro. Biochem Biophys Res
Commun 336: 444–449.
Ozaki Y. 1992. Antiinflammatory effect of tetramethylpyrazine and
ferulic acid. Chem Pharm Bull (Tokyo) 40: 954–956.
Pae HO, Jeong SO, Zheng M, et al. 2009. Curcumin attenuates
ethanol-induced toxicity in HT22 hippocampal cells by activat-
ing mitogen-activated protein kinase phosphatase-1. Neurosci
Lett 453: 186–189.
Pan MH, Huang TM, Lin JK. 1999. Biotransformation of curcumin
through reduction and glucuronidation in mice. Drug Metab
Dispos 27: 486–494.
Pan R, Qiu S, Lu DX, Dong J. 2008. Curcumin improves learning
and memory ability and its neuroprotective mechanism in
mice. Chin Med J (Engl) 121: 832–839.
Park SY, Kim DS. 2002. Discovery of natural products from
Curcuma longa that protect cells from beta-amyloid insult: a
drug discovery effort against Alzheimer's disease. J Nat Prod
65: 1227–1231.
Park SY, Kim HS, Cho EK, et al. 2008. Curcumin protected PC12
cells against beta-amyloid-induced toxicity through the inhibi-
tion of oxidative damage and tau hyperphosphorylation. Food
Chem Toxicol 46: 2881–2887.
Perkins S, Verschoyle RD, Hill K, et al. 2002. Chemopreventive ef-
ficacy and pharmacokinetics of curcumin in the min/+ mouse,
a model of familial adenomatous polyposis. Cancer Epidemiol
Biomarkers Prev 11: 535–540.
Qin NY, Yang FQ, Wang YT, Li SP. 2007. Quantitative determina-
tion of eight components in rhizome (Jianghuang) and tuber-
ous root (Yujin) of Curcuma longa using pressurized liquid
extraction and gas chromatography–mass spectrometry. J
Pharm Biomed Anal 43: 486–492.
Quitschke WW. 2008. Differential solubility of curcuminoids in se-
rum and albumin solutions: implications for analytical and ther-
apeutic applications. BMC Biotechnol 8: 84.
Qureshi S, Shah AH, Ageel AM. 1992. Toxicity studies on Alpinia
galanga and Curcuma longa. Planta Med 58: 124–127.
Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP.
1999. Neuroprotective role of curcumin from Curcuma
longa on ethanol-induced brain damage. Phytother Res 13:
571–574.
Rajeswari A. 2006. Curcumin protects mouse brain from oxidative
stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Eur Rev Med Pharmacol Sci 10: 157–161.
Rastogi M, Ojha RP, Rajamanickam GV, Agrawal A, Aggarwal A,
Dubey GP. 2008. Curcuminoids modulates oxidative damage
and mitochondrial dysfunction in diabetic rat brain. Free Radic
Res 42: 999–1005.
Rasyid A, Lelo A. 1999. The effect of curcumin and placebo on
human gall-bladder function: an ultrasound study. Aliment
Pharmacol Ther 13: 245–249.
Rasyid A, Rahman AR, Jaalam K, Lelo A. 2002. Effect of different
curcumin dosages on human gall bladder. Asia Pac J Clin Nutr
11: 314–318.
Ringman JM, Younkin SG, Pratico D, et al. 2008. Biochemical
markers in persons with preclinical familial Alzheimer disease.
Neurology 71: 85–92.
Sandur SK, Pandey MK, Sung B, et al. 2007. Curcumin,
demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin
and turmerones differentially regulate anti-inflammatory and anti-
proliferative responses through a ROS-independent mechanism.
Carcinogenesis 28: 1765–1773.
Copyright © 2013 John Wiley & Sons, Ltd.
Scott BC, Butler J, Halliwell B, Aruoma OI. 1993. Evaluation of the
antioxidant actions of ferulic acid and catechins. Free Radic
Res Commun 19: 241–253.
Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK. 2005. De-
sign, synthesis, biological evaluation and molecular docking of
curcumin analogues as antioxidant, cyclooxygenase inhibitory
and anti-inflammatory agents. Bioorg Med Chem Lett 15:
1793–1797.
Sethi P, Jyoti A, Hussain E, Sharma D. 2009. Curcumin attenuates
aluminium-induced functional neurotoxicity in rats. Pharmacol
Biochem Behav 93: 31–39.
Shankar TN, Shantha NV, Ramesh HP, Murthy IA, Murthy VS.
1980. Toxicity studies on turmeric (Curcuma longa): acute
toxicity studies in rats, guinea pigs & monkeys. Indian J Exp
Biol 18: 73–75.
Sharma D, Sethi P, Hussain E, Singh R. 2009a. Curcumin counter-
acts the aluminium-induced ageing-related alterations in oxi-
dative stress, Na(+), K(+) ATPase and protein kinase C in
adult and old rat brain regions. Biogerontology 10: 489–502.
Sharma S, Zhuang Y, Ying Z, Wu A, Gomez-Pinilla F. 2009b.
Dietary curcumin supplementation counteracts reduction in
levels of molecules involved in energy homeostasis after brain
trauma. Neuroscience 161: 1037–1044.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. 2008.
Epigallocatechin-3-gallate and curcumin suppress amyloid
beta-induced beta-site APP cleaving enzyme-1 upregulation.
Neuroreport 19: 1329–1333.
Shishu, Maheshwari M. 2010. Comparative bioavailability of
curcumin, turmeric and Biocurcumax™ in traditional vehicles
using non-everted rat intestinal sac model. J Functional Foods
2: 60–65.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
1998. Influence of piperine on the pharmacokinetics of curcumin
in animals and human volunteers. Planta Med 64: 353–356.
Shukla PK, Khanna VK, Khan MY, Srimal RC. 2003. Protective ef-
fect of curcumin against lead neurotoxicity in rat. Hum Exp
Toxicol 22: 653–658.
Shytle RD, Tan J, Bickford PC, et al. 2012. Optimized turmeric ex-
tract reduces beta-amyloid and phosphorylated tau protein
burden in Alzheimer's transgenic mice. Curr Alzheimer Res 9:
500–506.
Sreejayan, Rao MN. 1994. Curcuminoids as potent inhibitors of
lipid peroxidation. J Pharm Pharmacol 46: 1013–1016.
Sreejayan, Rao MN. 1997. Nitric oxide scavenging by curcuminoids.
J Pharm Pharmacol 49: 105–107.
Srinivasan M. 1972. Effect of curcumin on blood sugar as seen in a
diabetic subject. Ind J Med Sci 26: 269–270.
Srivastava R, Dikshit M, Srimal RC, Dhawan BN. 1985. Anti-
thrombotic effect of curcumin. Thromb Res 40: 413–417.
Suh YH, Checler F. 2002. Amyloid precursor protein, presenilins,
and alpha-synuclein: molecular pathogenesis and pharmaco-
logical applications in Alzheimer's disease. Pharmacol Rev
54: 469–525.
Tang H, Lu D, Pan R, Qin X, Xiong H, Dong J. 2009. Curcumin im-
proves spatial memory impairment induced by human immu-
nodeficiency virus type 1 glycoprotein 120 V3 loop peptide
in rats. Life Sci 85: 1–10.
Vagnucci AH, Jr., Li WW. 2003. Alzheimer's disease and angio-
genesis. Lancet 361: 605–608.
Venkatesan N. 1998. Curcumin attenuation of acute adriamycin
myocardial toxicity in rats. Br J Pharmacol 124: 425–427.
Wahlstrom B, Blennow G. 1978. A study on the fate of curcumin in
the rat. Acta Pharmacol Toxicol (Copenh) 43: 86–92.
Wang R, Li YB, Li YH, Xu Y, Wu HL, Li XJ. 2008. Curcumin pro-
tects against glutamate excitotoxicity in rat cerebral cortical
neurons by increasing brain-derived neurotrophic factor level
and activating TrkB. Brain Res 1210: 84–91.
Wang YJ, Thomas P, Zhong JH, et al. 2009. Consumption of grape
seed extract prevents amyloid-beta deposition and attenuates
inflammation in brain of an Alzheimer's disease mouse.
Neurotox Res 15: 3–14.
Xiong Z, Hongmei Z, Lu S, Yu L. 2011. Curcumin mediates presenilin-
1 activity to reduce beta-amyloid production in a model of
Alzheimer's disease. Pharmacol Rep 63: 1101–1108.
Yang F, Lim GP, Begum AN, et al. 2005. Curcumin inhibits forma-
tion of amyloid beta oligomers and fibrils, binds plaques, and
reduces amyloid in vivo. J Biol Chem 280: 5892–5901.
Yousef MI, El-Demerdash FM, Radwan FM. 2008. Sodium arsenite
induced biochemical perturbations in rats: ameliorating effect
of curcumin. Food Chem Toxicol 46: 3506–3511.
Phytother. Res. (2013)
 THERAPEUTIC POTENTIAL OF TURMERIC IN AD
Yu ZF, Kong LD, Chen Y. 2002. Antidepressant activity of aqueous
extracts of Curcuma longa in mice. J Ethnopharmacol 83:
161–165.
Zeng Y, Qiu F, Liu Y, Qu G, Yao X. 2007. Isolation and identification
of phase 1 metabolites of demethoxycurcumin in rats. Drug
Metab Dispos 35: 1564–1573.
Zhang C, Browne A, Child D, Tanzi RE. 2010a. Curcumin de-
creases amyloid-beta peptide levels by attenuating the matu-
ration of amyloid-beta precursor protein. J Biol Chem 285:
28472–28480.
Zhang L, Fiala M, Cashman J, et al. 2006. Curcuminoids enhance
amyloid-beta uptake by macrophages of Alzheimer's disease
patients. J Alzheimers Dis 10: 1–7.
Copyright © 2013 John Wiley & Sons, Ltd.
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Zhang L, Wu C, Zhao S, et al. 2010b. Demethoxycurcumin, a natural
derivative of curcumin attenuates LPS-induced pro-
inflammatory responses through down-regulation of intracellu-
lar ROS-related MAPK/NF-kappaB signaling pathways in N9
microglia induced by lipopolysaccharide. Int Immunopharmacol
10: 331–338.
Zhang LJ, Wu CF, Meng XL, et al. 2008. Comparison of inhibitory po-
tency of three different curcuminoid pigments on nitric oxide
and tumor necrosis factor production of rat primary microglia in-
duced by lipopolysaccharide. Neurosci Lett 447: 48–53.
Zhao J, Zhao Y, Zheng W, Lu Y, Feng G, Yu S. 2008.
Neuroprotective effect of curcumin on transient focal cerebral
ischemia in rats. Brain Res 1229: 224–232.
Phytother. Res. (2013)