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Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 313
IJP (2018), Vol. 5, Issue 6 (Review Article)
Received on 09 February, 2018; received in revised form, 21 March, 2018; accepted, 30 March, 2018; published 01 June, 2018
PHARMACOLOGICAL ASPECTS OF CURCUMIN: REVIEW ARTICLE
Ali Alsamydai * and Nisrein Jaber
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Jordan,
Amman, Jordan.
ABSTRACT: Turmeric (Curcuma longa) is widely used popular
Indian medicinal plant which belongs to the family of
Zingiberaceae. Curcumin, an important constituent of turmeric, is
known for various biological activities, primarily due to its
antioxidant mechanism. Epidemiological observations are
suggestive that turmeric consumption may reduce the risk of some
form of cancers and render other protective biological effects in
humans like antidiabetic, anti-inflammatory, anti-angiogenic, anti-
oxidant, wound healing and anti-cancer effects. This review
summarizes the most interesting biological effects of curcumin.
INTRODUCTION: Turmeric is an Indian
rhizomatous herbal plant (Curcuma longa) of the
ginger family (Zingiberaceae) of well-known
medical benefits 1, 2. Fig. 1 shows Curcuma longa.
The medicinal benefits of turmeric could be
attributed to the presence of active principles called
curcumin oids. One of the most interesting
components of curcumin oid is curcumin, which is
a small molecular weight polyphenolic compound
and lipophillic in nature, hence insoluble in water
and also in ether but soluble in ethanol,
dimethylsulfoxide, and other organic solvents 3.
Curcumin is stable at the acidic pH of the stomach
4. The other constituents present are volatile oils
including tumerone, atlantone and zingiberone and
sugars, proteins and resins 2. The active constituent
of turmeric- curcumin is isolated from curcuma
longa and it provides colour to turmeric.
QUICK RESPONSE CODE
DOI:
10.13040/IJPSR.0975-8232.IJP.5(6).313-326
Article can be accessed online on:
www.ijpjournal.com
DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.5(6).313-326
Such bioactive component has been thoroughly
investigated 5. Curcumin (1, 7-bis (4-hydroxy-3-
methoxyphenyl)-1, 6-heptadiene-3,5-dione) is also
called diferuloylmethane 6. It is a tautomeric
compound existing in enolic form in organic solvents
and as a keto form in water Fig. 2.
FIG. 1: CURCUMA LONGA
FIG. 2: CHEMICAL STRUCTURES OF CURCUMIN OIDS
Keywords:
Curcumin, Curcuma longa,
Zingiberaceae, Pharmacological uses,
Anticancer, Antidiabetic, Antioxidant
Correspondence to Author:
Ali Alsamydai
Department of Pharmaceutics
and Pharmaceutical Technology,
Faculty of Pharmacy, University of
Jordan, Amman, Jordan.
Email: Phalimahmoud2012@yahoo.com
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 314
It was found that curcumin oids in the herb C.
longa are synthesized by a collaboration of two
type III Polyketide synthases, diketide-CoA
synthase (DCS) and curcumin synthase 1 (CURS1,
the first identified CURS) (Fig. 3A). DCS catalyzes
formation of feruloyldiketide CoA (4) from
feruloyl-CoA (5) and malonyl-CoA. CURS1
catalyzes formation of curcumin from feruloyl-
CoA (5) and the feruloyldiketide-CoA produced by
the action of DCS (4). Thus, DCS and CURS1
catalyze the formation of curcumin. Both enzymes
accept p-coumaroyl-CoA (6), but at low efficiency,
and are also capable of synthesizing bisdemethoxy
curcumin (3) from p-coumaroyl-CoA (6) and
malonyl-CoA via p-coumaroyldiketide-CoA (7)
formation. Although a pair of DCS and CURS
produces a mixture of Curcumin oids; i.e., Curcumin
(1), demethoxyCurcumin (2) and bisdemethoxy
curcumin, from feruloyl-CoA (5), p-coumaroyl-
CoA (6) and malonyl-CoA in-vitro, it yields the
mixture of products with a composition different
from that of an ethyl acetate extract of the rhizome
of turmeric; the rhizome of turmeric contains a
relatively larger amount of bisdemethoxy curcumin
(3) than the in-vitro reaction products by a pair of
DCS and CURS. Therefore, it was assumed that the
composition of curcumin oids in the mixture might
be regulated by the concentrations of p-coumaroyl-
CoA and feruloyl-CoA in-vivo.
CURSs catalyze the formation of curcumin oids (1-
3) from cinnamoyl-CoA (10), p-coumaroyl-CoA
(6) and feruloyl-CoA (5), when incubated with
cinnamoyldiketide-N-acetylcysteamine (NAC) (8),
an analogue of diketide-CoA Fig. 3 137.
FIG. 3: THE BIOSYNTHESIS PATHWAY OF CURCUMIN OIDS
Turmeric is the boiled, dried, cleaned and polished
rhizomes of curcuma longa. After harvesting the
whole rhizomes are collected. These rhizomes are
transported as whole rhizomes. They are usually
like fingers 2 to 8 cm long and 1 to 2 cm wide
having bulbs and splits. The dried rhizomes are
further processed and reprocessed to obtain the
turmeric powder 2.
The use of turmeric dates back nearly 4000 years to
the Vedic culture in India, where it was used as a
culinary spice and had some religious significance
7. It has different names in different cultures and
countries. In North India, turmeric is commonly
called “haldi,” and in the south, it is called “manjal,”
It is known as terre merite in French and simply as
“yellow root” in many languages. In Arabic, it is
called Kurkum, Uqdah safra. In Sanskrit, turmeric
has at least 53 different names 7. Curcumin has
been used in tradition as a medical herb due to its
various advantages such as: antioxidant 8, anti-
inflammatory 9 antimutagenic 10, antimicrobial 11
and several therapeutic properties 12. Curcumin
shows poor absorption, rapid metabolism, and rapid
elimination. Several agents have been introduced to
improve the bioavailability of curcumin. Most
interesting one is piperine, it enhances curcumin
bioavailability by blockage of the metabolic
pathway of curcumin 13.
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 315
Pipierine results in an increase of 2000% in the
bioavailability of curcumin 14.
Curcumin is available in several forms including
capsules, tablets and ointments 15. Curcumin oids
have been approved by the US Food and Drug
Administration (FDA) as “Generally Recognized as
Safe” (GRAS) 16. It is the purpose of this review to
provide a brief overview of the potential health
benefits of curcumin.
Medicinal Uses of Curcumin:
Anti-Diabetic Activity: Curcumin was reported to
possess anti-diabetic activity. The effect of anti-
diabetic activity could be attributed to the
antioxidant property of curcumin 17. In their study,
researchers demonstrated curcumin positive effect
through the improvement of diabetes-induced
endothelial dysfunction by decreasing superoxide
production and vascular protein kinase C inhibition.
Interestingly, recent studies demonstrated the ability
of curcumin to have the capacity to directly quench
reactive oxygen species (ROS) that can contribute
to oxidative damage 18.
This property is known to contribute to the overall
protective effects of curcumin. Curcumin can
attenuate cell death caused by oxidative stress,
indirectly through induction and/or activation of
antioxidant/ cytoprotective enzymes, such as heme
oxygenase-1 (HO-1). The protective mechanisms of
HO-1 in diabetes could present some emerging
therapeutic options for HO-1 expression in treating
diabetic diseases 18.
Curcumin was evaluated for the prevention of type
2 diabetes in pre-diabetic human population 19. The
subjects received curcumin capsules for 9 month
period versus placebo capsule group. The curcumin
-treated group showed a better overall function of
β-cells, with higher HOMA-β and lower C-peptide.
The curcumin treated group showed a lower level
of HOMA-IR and higher adiponectin, when
compared with the placebo group. The results
indicated that curcumin intervention may have
positive effect to a prediabetic population 19.
Wound Healing Activity: Wound healing includes
the repair of tissues in a complex process that
involves inflammation, granulation, and remodeling
of the tissue 20. Enhancement of wound healing was
reported by curcumin in animals. The mechanisms
of action of wound healing effect of curcumin
include: immunohistochemical localization of
transforming growth factor-β1 showed an increase
in curcumin-treated wounds as compared with
untreated wounds 22 and modulating collagen and
decreasing reactive oxygen species 21.
In addition, curcumin showed earlier re-
epithelialization, improved neovascularization,
increased migration of various cells including
dermal myofibroblasts, fibroblasts, and
macrophages into the wound bed, and higher
collagen content 22, 23.
Anti-arthritis Activity: Rheumatoid arthritis (RA)
is a chronic inflammatory disease that is
characterized by hyperplasia of the synovial
fibroblasts. Curcumin is known to possess potent
anti-inflammatory and anti-arthritic properties 24.
Curcumin treatment was carried out on patients
with active rheumatoid arthritis and compared with
diclofenac sodium reference group. Interestingly,
the curcumin group showed the highest percentage
of improvement in overall rheumatoid arithritis
scores and these scores were significantly better
than the patients in the diclofenac sodium group.
More importantly, curcumin group was found to be
safe and did not relate with any adverse events
compared to diclofenac sodium group 25.
It is believed that curcumin antioxidant anti-
proliferative, anti-inflammatory and immune-
suppressive activities shared in the improvement of
symptoms to patients suffering from rheumatoid
arthritis 26. One of the important consequences of
RA could be the decreased apoptosis. Exposure of
the synovial fibroblasts to curcumin resulted in
growth inhibition and the induction of apoptosis, as
measured by MTT assay, fluorescent microscopy
and Annexin-V-based assay. These results show
that curcumin might help against hyperplasia of the
synovial fibroblasts in RA 27.
Anti-Alzheimer Activity: Alzheimer disease (AD)
is by far the most common cause of dementia
globally. This neurodegenerative disorder of the
brain is chronic and progressive, characterized
clinically by the deterioration in the key symptoms
of behavioral and cognitive abilities. Researchers
reported the advantages of curcumin oids as anti-
alzheimer agents 28.
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International Journal of Pharmacognosy 316
Curcumin action was demonstrated through the
inhibition of the accumulation of amyloid β-peptide
(Aβ) and the formation of β-amyloid fibrils (fAβ)
from Aβ, as well as the destabilization of
preformed fAβ in the central nervous system.
Consequently, curcumin would be an attractive
therapeutic target for the treatment of Alzheimer's
disease 29.
Anti-Parkinson Activity: Oxidative stress has
been implicated in the degeneration of
dopaminergic neurons in the substantia nigra (SN)
of Parkinson's disease (PD) patients. An important
biochemical feature of presymptomatic PD is a
significant depletion of the thiol antioxidant
glutathione (GSH) in these neurons resulting in
oxidative stress, mitochondrial dysfunction, and
ultimately cell death. Curcumin restores depletion
of GSH levels, protects against protein oxidation,
and preserves mitochondrial complex I activity
which normally is impaired due to GSH loss. Thus,
it helps in treatment of PD 30.
Overexpression and abnormal accumulation of
aggregated α-synuclein (αS) have been linked to
Parkinson's disease (PD) and other synucleinopathies.
αS can misfold and adopt a variety of morphologies
but recent studies implicate oligomeric forms as the
most cytotoxic species. Curcumin can alleviate αS-
induced toxicity, reduce intracellular reactive
oxygen species ROS levels and protect cells against
apoptosis. Thus, curcumin could be used as anti-
Parkinson 31.
Anti-inflammatory Activity: Curcumin possesses
significant anti-inflammatory activity in acute as
well as in chronic models of inflammation. It is as
potent as phenylbutazone in the carrageenan
oedema test but only half as potent in chronic
tests 32. Curcumin has been demonstrated to be safe
in six human trials and has demonstrated anti-
inflammatory activity. It may exert its anti-
inflammatory activity by inhibition of a number of
different molecules that play a role in inflammation
33. Curcumin has been shown to regulate numerous
transcription factors, cytokines, protein kinases,
adhesion molecules, redox status and enzymes that
have been linked to inflammation 24.
Anti-Venom Activity: Curcumin was listed as a
herbal plant metabolite that can effective against
Snake Venom PLA2 34. Researchers studied the
structural relationship between medicinally
important herbal compounds such as acalyphin,
chlorogenic acid, stigmasterol, curcumin and
tectoridin and PLA2 from Russell's viper. The
molecular modeling studies revealed favorable
interactions with the amino acid residues at the
active site of venom PLA2 that could result in the
inhibition 35.
Anti-Angiogenesis Activity: Curcumin was tested
for its ability to inhibit the proliferation of primary
endothelial cells in the presence and absence of
basic fibroblast growth factor (bFGF), as well as its
ability to inhibit proliferation of an immortalized
endothelial cell line. Curcumin was tested for its
ability to inhibit phorbol ester-stimulated vascular
endothelial growth factor (VEGF) mRNA
production 36. Curcumin effectively inhibited
endothelial cell proliferation in a dose-dependent
manner. Curcumin demonstrated significant
inhibition of bFGF-mediated corneal neovascu-
larization in the mouse. Curcumin had no effect on
phorbol ester-stimulated VEGF production. These
results indicate that curcumin has direct anti-
angiogenic activity in-vitro and in-vivo 37.
Anti-Oxidant Activity: Curcumin demonstrated
the antioxidant activity by evaluation curcumin
using various in-vitro antioxidant assays such as
1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH)
scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-
sulfonic acid) (ABTS) radical scavenging
activity, N,N-dimethyl-p-phenylenediamine dihydro-
chloride (DMPD) radical scavenging activity, total
antioxidant activity determination by ferric
thiocyanate, total reducing ability determination by
the Fe3+– Fe2+ transformation method, superoxide
anion radical scavenging by the riboflavin/
methionine/illuminate system, hydrogen peroxide
scavenging and ferrous ions (Fe2+) chelating
activities 38.
Protective against Cardio Toxicity and Liver
Toxicity: Researchers investigate the protective
effects of curcumin on experimentally induced
hepatotoxicity, and cardio toxicity using various
animal models with biochemical parameters like
serum marker enzymes and antioxidants in target
tissues. The increased relative weight of liver and
heart in CCl4 induced liver injury and isoproterenol
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 317
induced cardiac necrosis were also reduced by
Curcumin treatment. Elevated serum marker
enzymes, aspartate aminotransferase (AST),
alanine aminotransferase (ALT) and alkaline
phosphatase (ALP) increased lipid peroxidation,
decreased gluthione (GSH), glutathione peroxidase
(GPx) and superoxide dismutase (SOD) in
edematous, granulomatus, liver and heart tissues
during liver injury and cardiac necrosis,
respectively. The study demonstrated the in-
vitro and in-vivo protective effect of curcumin on
experimentally induced hepatotoxicity and cardio-
toxicity in rats 39.
Anti-Bacterial Activity: The antibacterial study of
curcumin shows the ability to inhibit growth of a
variety of periodontopathic bacteria and
Porphyromonas gingivitis Arg- and Lys-specific
proteinase (RGP and KGP, respectively) activities
63. In addition, curcumin suppressed P. gingivitis
homotypic and Streptococcus gordonii biofilm
formations in a dose-dependent manner 64. Bacterial
growth was suppressed almost completely at very
low concentrations of curcumin. A concentration of
20 µg/mL of curcumin inhibited these P. gingivitis
biofilm formations by more than 80%. On the other
hand, 100 µg/mL of curcumin did not suppress the
growth of Aggregatibacter actinomycetemcomitans
63. Furthermore, at relatively high concentrations,
curcumin targets bacterial membranes (Escherichia
coli).
Additionally, many features of a bacterial apoptosis
-like response were observed after treatment with
curcumin at the MIC, including membrane
depolarization, Ca 2+ influx, PS exposure and DNA
fragmentation. A bacterial apoptosis-like response,
induced by curcumin, by causing reactive oxygen
species generation and DNA damage 65. The study
on E. coli and B. subtilis demonstrated that
curcumin by the inhibitory effect against FtsZ
polymerization could suppress the FtsZ assembly
leading to disruption of prokaryotic cell division 66.
On another hands, Curcumin - Polymyxin B used
clinically for topical therapy to treat or prevent
traumatic wound infections of the skin. It would
not only increase the spectrum of activity to include
Gram-positive bacteria but also combat those
isolated resistant. The use of the combination may
also reduce the emergence of resistant isolates
during treatments, due to the multiple antimicrobial
targets of duel drug therapy and ease the selective
pressure produced by broad-spectrum antibiotics 67.
Additionally, curcumin loaded in zein (zein-CUR)
fibers showed good antibacterial activity towards S.
aureus and E. coli and the inhibition efficiency
increased with the increase of curcumin contents.
Due to the different cell membrane constituent and
structure, the antibacterial activity towards S.
aureus was better than that towards E. coli. The
study displayed that the zein-CUR fibers might
have potential as a promising material for
antimicrobial applications to inhibit bacterial
growth and propagation in food packaging 68. Also,
antibacterial activity of curcumin-chitosan film
against Staphylococcus aureus and Rhizoctonia
solani was studied by the zone inhibition method
69. A better antibacterial activity was certified
compared to PCH film, which is an important
consideration in food packaging. The natural blend
films of curcumin and chitosan could be as a
promising antimicrobial packaging for food and
agriculture products 70.
Novel fibrous materials from cellulose acetate (CA)
and polyvinylpyrrolidone (PVP) contain curcumin.
The incorporation of PVP resulted in increased
hydrophilicity of the fibers and in faster curcumin
release. Likewise, curcumin was found in the
amorphous state in the curcumin containing fibers
and these mats exhibited antibacterial activity
against Staphylococcus aureus (S. aureus). The
Curc/CA+Curc/PVP mat prepared by dual-
spinneret electrospinning killed all the bacteria at
the 4 h. Curcumin fibrous materials are potential
antibacterial for wound dressing applications 71.
In addition, Surface charge as well as the small size
of curcumin nanoparticles plays a key role in
enhancing cell-antimicrobial interaction and anti-
microbial efficacy. The fabricated curcumin nano-
particles showed the best antimicrobial activity
against Listeria monocytogenes. A size reduction to
nano-scale is a recently developed strategy used to
improve drug/food delivery and matching the
public demand for effective and safe antimicrobial
formulations for control of food borne pathogen 72.
In-vivo study of antibacterial effect of curcumin on
H. pylori compared to OAM (Omeprazole,
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 318
Amoxicillin and Metronidazole) treatment revealed
poor activity for eradication of H. pylori (5.9%
versus 78.9% for OAM treatment). The reduction
in inflammatory cytokine production was not
reported from pylori-infected patients treated with
curcumin 73. The in-vivo study of 1-week
nonantibiotic therapy comprised of curcumin,
pantoprazole, N-acetylcysteine, and lactoferrin
against H. pylori infection was not effective for the
eradication of H. pylori. However, the decrease in
immunological criteria of gastric inflammation and
dyspeptic symptoms was reported after 2 months of
treatment schedule 74.
Nevertheless, the curcumin administration to the
rats with H. pylori-induced gastric inflammation
revealed a significant reduction in macromolecular
leakage and NF activation 75. In an in-vivo study of
H. pylori-infected C57BL/6 mice administered with
curcumin exhibited immense therapeutic potential
and pronounced eradication effect against H. pylori
infection associated with restoration of gastric
damage 76.
Anti-Fungal Activity: Substances and extracts
isolated from different natural resources especially
plants have always been a rich arsenal for
controlling the fungal infections and spoilage. Due
to extensive traditional use of curcumin in food
products, various researches have been done in
order to study curcumin with the aspect of controlling
fungal related spoilage and fungal pathogens 77.
The study of addition the curcumin powder in plant
tissue culture showed that curcumin at the 0.8 and
1.0 g/L had appreciable inhibitory activity against
fungal contaminations 78. The possible mechanism
underlying the mentioned antifungal effect was
found to be downregulation of desaturase (ERG3)
leading to significant reduction in ergosterol of
fungal cell. Reduction in production of ergosterol
results in accumulations of biosynthetic precursors
of ergosterol which leads to cell death via
generation of ROS 138. Reduction in proteinase
secretion and alteration of membrane-associated
properties of ATPase activity are other possible
critical factors for antifungal activity of curcumin
79. Finding new anti-candida substances seems to
be crucial due to development of resistant strain
against existing antifungal drug 56. The study of
curcumin, against 14 strains of Candida, showed
that curcumin is a potent fungicide compound
against Candida species with MIC values range
from 250 to 2000 μg/mL 79.
In another study, anti-candida activity of curcumin
was demonstrated against 38 different strains of
Candida including some fluconazole resistant
strains and clinical isolates of C. albicans, C.
glabrata, C. tropicalis, C. guilliermondii, and C.
krusei. The MIC90 values for sensitive and resistant
strains were 250-650 and 250-500 μg/mL, res-
pectively. Intracellular acidification via inhibition
of H+-extrusion was identified as possible
mechanism for cell death of Candida species 80.
The development of hyphae was proved to be
inhibited by curcumin through targeting the global
suppressor thymidine uptake 1 (TUP1). Curcumin
exhibited potent antifungal effect via mechanisms
associated with disruption of plasma membrane
in Candida albicans 81.
Curcumin also showed inhibitory effect on
Cryptococcus neoformans and C. dubliniensis with
MIC value of 32 mg/L 79. One of the major
complications during therapies against chronic
asthma is oropharyngeal candidiasis. Curcumin as a
potential candidate for the treatment of candidiasis
with anti-inflammatory activity was studied in a
murine model of asthma. Oral administrator of
curcumin is more effective than dexamethasone in
reducing fungal burden in BALB/c mice. It also
significantly decreased pathological changes in
asthma 82. Adhesion of Candida species isolated
from AIDS patients to buccal epithelial cells is also
markedly inhibited by curcumin and it was found to
be more effective compared to fluconazole 83.
The investigation of curcumin mediation for photo-
dynamic therapy can reduce the biofilm biomass
of C. albicans, C. glabrata and C. tropicalis. The
results demonstrated that association of four LED
influences for light excitation with 40 μM
concentration of curcumin at 18 J/cm2 inhibited up
to 85% metabolic activity of the tested Candida
species. The use of curcumin with light proved to
be an effective method for noteworthy improvement
in the antifungal activity against planktonic form of
the yeasts 84. Photodynamic effect considerably
decreased C. albicans viability in either planktonic
or biofilm cultures probably through increasing the
uptake of curcumin by cells. However, to a lesser
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International Journal of Pharmacognosy 319
extent, photodynamic therapy was found to be
phototoxic to the macrophages 85.
The strong antifungal activity of C. longa rhizome
and its low side effect were the main reasons to
investigate its probable synergistic effect with
existing fungicides. The synergistic activity of
curcumin with five azole and two polyene drugs
including voriconazole, itraconazole, ketoconazole,
miconazole, fluconazole, amphotericin B and
nystatin showed 10-35-fold reduction in the MIC
values of the fungicides against 21 clinical isolates
of C. albicans. The synergistic activity of curcumin
with amphotericin B and fluconazole could be
associated with the accumulation of ROS which
will be suppressed by adding an antioxidant 46.
Anti-Viral Activity: Lack of effective therapeutics
for the most of viral diseases, emergence of
antiviral drug resistance and high cost of some
antiviral therapies necessitate finding new effective
antiviral compounds 57, 58. Additionally, the existing
antiviral therapies are not always well-tolerated or
quite effective and satisfactory 46. Hence, the
increasing requirement for antiviral substances will
be more highlighted. Plants as a rich source of
phytochemicals with different biological activities
including antiviral activities are in interest of
scientists 59.
It has been demonstrated that curcumin as a plant
derivative has a wide range of antiviral activity
against different viruses: papillomavirus virus
(HPV), influenza virus, Hepatitis B virus (HBV),
Hepatitis C virus (HCV), adenovirus, coxsackie virus,
Human norovirus (HuNoV), Respiratory syncytial
virus (RSV) and Herpes simplex 1 (HSV-1) 86, 87,
88, 89, 90. Curcumin functionalized graphene oxide
shown synergistic antiviral effect against
respiratory syncytial virus infection 87. Respiratory
syncytial virus (RSV), which is considered as the
major viral pathogen of the lower respiratory tract
of infants, has been implicated in severe lung
disease 86.
Developing a β-cyclodextrin (CD) functionalized
graphene oxide (GO) composite, which displayed
excellent antiviral activity and curcumin loading
efficiently, showed that the composite could
prevent RSV from infecting the host cells by
directly inactivating virus and inhibiting the viral
attachment, which possessed the prophylactic and
therapeutic effects towards virus 86. The antiviral
effect of curcumin was a dose-dependent manner
91. Curcumin inhibit activity of inosine-mono
phosphate dehydrogenase (IMPDH) enzyme in
either noncompetitive or competitive manner. By
inhibition of IMPDH this led to reduce the level of
intracellular guanine nucleotides which required for
adequate RNA and DNA synthesis 86, 88, 92.
Curcumin mechanism involve in viral entry or
other life cycle stages rather than the replication of
viral RNA 91. Therefore, by inhibition of IMPDH
Curcumin have potential anti-proliferative, antiviral
and antiparasitic effects 92.
Anti-Cancer Activity: Cancer is the second largest
single cause of death claiming over six million
lives every year worldwide 93. Scientific studies of
plants used in various types of ethnic medicine
have led to the discovery of many valuable drugs,
including taxol, camptothecin, vincristine and
vinblastine 94, 44. Many studies pointed out
anticancer activities of curcumin alone or in
combination with conventional chemotherapy
drugs in treatment of cancer and its cancer-related
complications 94, 95, 96, 97. In-vitro and in-vivo studies
have indicated that curcumin prevents car-
cinogenesis by affecting two primary processes:
Angiogenesis and tumor growth 96, 97 98. Curcumin
has exhibited efficient anticancer and antifungal
activities alone or in combination with conventional
chemotherapy drugs and antifungal agents 99.
Curcumin analogs S1- S3 containing sulfone
strongly inhibited the growth of human prostate,
colon, lung and pancreatic cancer cells 100, 101.
FIG. 4: STRUCTURE OF CURCUMIN ANALOGS
CONTAINING SULFONE
Curcumin significantly inhibited the growth of
human breast cancer cell by inducing apoptosis in a
dose and time dependent manner, accompanied by
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International Journal of Pharmacognosy 320
a decrease in MCF-7 cell viability 98. The antitumor
action of curcumin is mediated via its anti-
proliferative effect in multiple cancers, inhibitory
action on transcription factors and downstream
gene products, modulatory effect on growth factor
receptors and cell adhesion molecules involved in
angiogenesis, tumor growth and metastasis, while
recent works showed the possibility curcumin
could exert its antitumor potential by telomerase
inhibition 102, 103 , 104. Curcumin oil have bi-functional
effects by blocking anti-apoptotic signaling but also
blocking anti-oncogenic signaling and interferon-γ
production 105, 106. Moreover, Curcumin showed a
higher uptake in tumor cells compared to normal
cells, suggesting potential diagnostic applications
in this field 107.
In a study, the Gallium-Curcumin complexes
showed an uptake in A549 lung cancer cells, at
least equivalent to the respective free curcumin,
confirming potential applications as cancer-
detecting radiotracers. Natural products play a
major role in chemotherapy drugs, and primarily
target proliferating tumor cells 94. Their use could
be of great interest and is considered to be an
inexpensive, safe and accessible approach to cancer
control and management. However, in spite of the
useful biological activities of curcumin but it
limited due to its poorly bioavailability, water
solubility and some possible adverse effects 96, 109.
The development of formulations of curcumin in
the form of nanoparticles, liposomes, micelles, or
phospholipid complexes to enhance its bio-
availability and efficacy is still in its early stages
110. Various nano-sized curcumin delivery systems,
such as nanoparticles, nanospheres, solid lipid
nanoparticles, micelles, and liposomes have been
shown to overcome these shortcomings and
significantly improve the anticancer and antifungal
activities of curcumin. Many studies on curcumin
and its nanoformulations are still in the preclinical
stage at present 110, 111.
PLGA curcumin nanoparticles efficiently inhibit
growth of prostate cancer cells both in-vitro and in-
vivo. This was achieved through lysosomal activity,
apoptosis, and inhibition of Androgen receptor and
nuclear b-catenin activity. PLGA-CUR NPs
significantly modulate the expression of miR-21
and miR-205 genes. Shown significant prostate
tumor specific targeting in a xenograft mouse
model 112. Curcumin exhibits the ability to
modulate multiple targets via the regulation of
diverse transcription factors, inflammatory
cytokines, growth factors, different protein kinases,
and various other enzymes. Furthermore, safety and
tolerability as evidenced by multiple clinical trials
carried out thus far together with cost-effectiveness
are some other added yet inevitable advantages
offered by this agent 113.
Delay of Cataract Development: Cataract is
responsible for more than one third of blindness
worldwide. Twenty-five percent of people over the
age of 65 and 50% of people larger than an age of
80 have a serious defeat of vision due to cataracts
114, 115. Cataract extraction surgery is the majority
treatment for cataract. Whereas cataract surgery is
considered to be not dangerous and mature,
irreversible blindness is a possible risk. There is no
recognized drug which can treat or overturn
cataract. If cataract onset is late by 10 years, it is
expected to decrease the risk for cataract surgery by
50%. Thus, much emphasis is being laid on
identifying compounds with high effectiveness and
low toxicity that can either avoid the onset or delay
cataract progression.
It is supposed that oxidative damage to the eye lens
responsible to the development of different kinds of
cataracts 116. The antioxidant characteristics of
curcumin are the main anti-cataract mechanism 117.
In cultured human lens epithelial cells (hLECs) in-
vitro, curcumin inhibit peroxiredoxin 6 (a pleiotropic
oxidative stress-response protein). By reversing the
activity of increasing the activities of superoxide
dismutase (SOD), decreasing ROS, and antioxidant
enzymes, the bioactive derivatives of curcumin
were reported to inhibit the selenite inducing
cataract 118, 119, 120.
Additionally, curcumin was found to have a
protective effect against cataract development
and/or progression of diabetic cataract in
numerous in-vitro and in-vivo cataract models 120,
121. Vitamin C is a potent non-enzymic antioxidant,
and the level of Vitamin C is high in human lens,
suggesting that Vitamin C may have a preventive
role in cataract progression. The decreased levels of
Vitamin C linked with selenite-induced rat
cataracts. So by administration of Curcumin was
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 321
found to increase Vitamin C levels so protect rat
eyes 122. Pretreatment of curcumin may prevent
oxidative damage and delay the development of
cataracts 118.
Hepatoprotective Activity: The liver is one of the
most important organs of the body, that plays an
important role in maintaining various physiological
processes and is involved in numerous vital
functions, such as metabolism, secretion, and
storage 123. Also participating in the biochemical
processes of growing, providing nutrients,
supplying energy, and reproducing.
In addition, it aids in the metabolism of
carbohydrates and fats, in the secretion of bile, and
in the storage of Vitamins It plays a central role in
detoxify endogenous (waste metabolites) and/or
exogenous (toxic compounds) substances of
organisms, as well as for synthesize useful agents,
has been analyzed since the 1970s by many
researchers. Curcumin has been discussed by
various researchers for their hepatoprotective. New
evidence has proven hepatoprotective activity of
curcumin, but its underlying mechanisms remain to
be elucidated.
Phytosome Curcumin had a strong protective effect
against paracetamol-induced with acute hepatic
damage in mice. The hepatoprotective effect of
phytosome curcumin may be explained by
increasing levels of antioxidant enzymes and
decreasing the lipid peroxidation and liver enzyme
on paracetamol-induced damage in mice.
Furthermore, in investigation of the protective
effect of curcumin on hepatic damage via
measuring the antioxidant capacity and regulation
of different enzymes. Curcumin treatment of bile
duct ligated rats led by elevation of antioxidant
(thiols, SOD and catalase) and hepatic enzymes
(ALP, AST and ALT). And Curcumin attenuated
liver damage through down-regulating of Ras-
related C3 botulinum toxin substrate 1, Rac1-GTP,
and NADPH oxidase 1 as well as reducing oxidative
stress in serum and liver tissue of BDL rats.
Curcumin may serve as effective hepatoprotective
agents for mercuric chloride-induced
hepatotoxicity. The protective effect is due to their
free radical scavenging activities and recovery of
antioxidant enzymes and function markers of the
liver. In additionally, the protective effects of
curcumin against Diethyl Nitrosamine induced
hepato- carcinogenesis in albino rats is due to
modulated the hepatic pathological alteration, liver
function enzymes serum levels, induced the hepatic
anti-oxidant system and suppressed the
prionflamatory cytokines.
Anti-Fibrotic Activity: Idiopathic pulmonary
fibrosis (IPF) is a progressive disease of unknown
etiology that can result in respiratory failure. The
resulting fibrotic changes in lung architecture lead
to decreased gas exchange and pulmonary
compliance. Notably, curcumin effectively
reduces profibrotic effects in fibroblasts in-vitro via
the inhibition of key steps in the signaling pathway
of transforming growth factor beta (TGF-b) a
multifunctional cytokine belonging to the
transforming growth factor.
It was reported that the activation of peroxisome
proliferator-activated receptor gamma (PPAR-g) by
curcumin blocked platelet derived growth factor
(PDGF) signaling pathway in hepatic satellites
cells. However, the relationship of PPAR- g and
PDGF signaling pathway is unclear in TGF-b
induced differentiation of lung fibroblasts to
myofibroblasts. Curcumin inhibits TGF-β2 driven
differentiation of mouse lung fibroblasts to
myofibroblasts. Curcumin and PPAR-γ could
potentially be used for effective treatment of IPF.
Anti-Atherosclerosis and Anti-hypertension
Activity: Atherosclerosis and hypertension can
potentially progress into dangerous cardiovascular
diseases such as myocardial infarction and stroke.
Statins are widely used to lower cholesterol levels
while antihypertensive agents such as captopril are
widely prescribed to treat high blood pressure.
Curcumin, a phenolic compound isolated
from Curcuma domestica, has been proven
effective for a broad spectrum of diseases,
including hypertension and hypercholesterolemia.
Therefore, curcumin is quite promising as an
alternative therapeutic compound. By studying the
effects of Curcumin on hyperlipidemia and hepatic
steatosis in high-fructose-fed wistar rats, the results
showed the ability of curcumin in treatment high-
fructose induced fatty liver, lipid derangements and
obesity through modulation of lipid metabolism in
the liver as evidenced by decreased expression of
Alsamydai and Jaber, IJP, 2018; Vol. 5(6): 313-326. E- ISSN: 2348-3962, P-ISSN: 2394-5583
International Journal of Pharmacognosy 322
lipogenic enzymes and transcription factors.
Therefore, it is suggested that the use of curcumin
may be beneficial as an adjuvant in the prevention
and management of diet-induced obesity and its
associated complications.
Another study reported that encapsulated of
curcumin in a nanoemulsion showed significant
cholesterol-lowering activity compared to a
standard drug, pravastatin and this encapsulated
increased not only the 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibition, but also
Angiotensin converting enzyme inhibitors like
effect by producing vasodilation by inhibiting the
formation of angiotensin II. These effects are
suggested to be the result of improved solubility in
the nanoemulsion system.
CONCLUSION: The wisdom and scientific
knowledge of curcumin, a highly pleiotropic agent,
which were used for its therapeutic effects in many
countries as traditional medicine. For that the
pharmacological properties and applications of
curcumin is a rapidly growing, progressing, and
expanding enterprise, as evidenced by the studies
reviewed above and the many more being reported
every day.
Of the most obvious therapeutic weight of
curcumin, researchers typically pointed at diseases
like diabetes, wound healing, arthritis, alzheimer,
parkinson, inflammatory, venom, angiogenesis,
cataract, cancer, atherosclerosis and hypertension
etc, which is in use since ages owing to its multiple
pharmacological activities. Curcumin is enriched
with many useful phytoconstituents, which are
responsible for its efficacy proven by experimentally
and clinically. It has been established beneficial in
treating anti-inflammatory, anti-allergic, anti-
oxidant, anti-hyperglycaemic, anti-cancer, anti-
microbial, antiatherosclerosis and anti-hypertension
properties. Because of curcumin facility to affect a
large range of molecular targets and a good safety
profile, was established to be a potential candidate
for the avoidance or/and treatment of a number of
diseases.
ACKNOWLEDGEMENT: We respect and thank
Prof. Dr. Mohammad Hudaib for providing us an
opportunity to do the project work in
(Pharmacological Aspects of Curcumin: Review
article) and giving us all support and guidance
which made us complete the project duly. We are
extremely thankful to Dr. Mayada Shihadeh for
providing such a nice support and guidance.
CONFLICT OF INTEREST: Nil
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How to cite this article:
Alsamydai A and Jaber N: Pharmacological aspects of curcumin: review article. Int J Pharmacognosy 2018; 5(6): 313-26. doi link:
http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.5(6).313-26.
