ArticlePDF AvailableLiterature Review

Abstract

Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has strong antioxidative, anti-inflammatory, and antibacterial properties. Due to these properties, curcumin has been used as a remedy for the prevention and treatment of skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin cancer. Curcumin has protective effects against skin damage caused by chronic ultraviolet B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its low bioavailability, limited aqueous solubility, and chemical instability. In this regard, the present review is focused on recent studies concerning the use of curcumin for the treatment of skin diseases, as well as offering new and efficient strategies to optimize its pharmacokinetic profile and increase its bioavailability.
Received: 23 February 2018
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Accepted: 28 June 2018
DOI: 10.1002/jcp.27096
REVIEW ARTICLE
Evidence of curcumin and curcumin analogue effects in skin
diseases: A narrative review
Yunes Panahi
1
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Omid Fazlolahzadeh
2
|
Stephen L. Atkin
3
|
Muhammed Majeed
4
|
Alexandra E. Butler
5
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Thomas P. Johnston
6
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Amirhossein Sahebkar
7,8,9
1
Chemical Injuries Research Center, Systems
Biology and Poisonings Institute, Baqiyatallah
University of Medical Sciences, Tehran, Iran
2
Department of Chemistry, Faculty of Science,
K. N. Toosi University of Technology, Tehran, Iran
3
Weill Cornell Medicine Qatar, Doha, Qatar
4
Sabinsa Corporation, East Windsor, New Jersey
5
Life Sciences Research Division, AntiDoping
Laboratory Qatar, Doha, Qatar
6
Division of Pharmaceutical Sciences, School
of Pharmacy, University of MissouriKansas
City, Kansas City, Missouri
7
Biotechnology Research Center, Pharmaceutical
Technology Institute, Mashhad University of
Medical Sciences, Mashhad, Iran
8
Neurogenic Inflammation Research Center,
Mashhad University of Medical Sciences,
Mashhad, Iran
9
School of Pharmacy, Mashhad University of
Medical Sciences, Mashhad, Iran
Correspondence
Omid Fazlolahzadeh, Department of Chemistry,
Faculty of Science, K. N. Toosi University of
Technology, 163151618, Tehran, Iran.
Email: o.fazlolahzadeh@gmail.com
Amirhossein Sahebkar, Department of Medical
Biotechnology, School of Medicine, Mashhad
University of Medical Sciences, Mashhad
9177948564, Iran.
Email: sahebkara@mums.ac.ir;
amir_saheb2000@yahoo.com
Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has
strong antioxidative, antiinflammatory, and antibacterial properties. Due to these
properties, curcumin has been used as a remedy for the prevention and treatment of
skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin
cancer. Curcumin has protective effects against skin damage caused by chronic ultraviolet
B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its
low bioavailability, limited aqueous solubility, and chemical instability. In this regard, the
present review is focused on recent studies concerning the use of curcumin for the
treatment of skin diseases, as well as offering new and efficient strategies to optimize its
pharmacokinetic profile and increase its bioavailability.
KEYWORDS
curcumin, dermatology, inflammation, skin, topical use
J Cell Physiol. 2018;114. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc.
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Abbreviations: 5LOX, 5lipoxygenase; AAPK, autophosphorylationactivated protein kinase; AATF1, arylamine Nacetyltransferases 1; AHR, aryl hydrocarbon receptor; AP1, activating
protein 1; AR, androgen receptor; Bcl2, Bcell lymphoma protein 2; Ca
2+
PK, Ca
2+
dependent protein kinase; CKCR4, chemokine (CXC motif) receptor 4; COX2, cyclooxygenase 2; CREBBP,
CREBbinding protein; CTGF, connective tissue growth factor; DFF40, DNA fragmentation factor 40 kDa subunit; DNA Pol, DNA polymerase; DR5, death receptor 5; EGF, epidermal growth
factor; EGFR, EGF receptor; EGFRK, EGF receptor kinase; ELAM1, endothelial leukocyte adhesion molecule 1; EPCR, endothelial protein C receptor; ERE, electrophile response element; ERK,
extracellular receptor kinase; ERα, estrogen receptorα; FAK, focal adhesion kinase; FGF, fibroblast growth factor; FPT, farnesyl protein transferase; FR, Fas receptor; GCL, glutamyl cysteine
ligase; GST, gluthathioneStransferase; H2R, histamine (2) receptor; HER2, human epidermal growth factor receptor 2; HGF, hepatocyte growth factor; HIF1, hypoxiainducible factor 1; HO,
hemeoxygenase 1; HSP70, heatshock protein 70; IAP1, inhibitory apoptosis protein 1; ICAM1, intracellular adhesion molecule 1; IL1, interleukin 1; IL12, interleukin 12; IL18, interleukin
18; IL1R AK, IL1 receptorassociated kinase; IL2, interleukin 2; IL5, interleukin 5; IL6, interleukin 6; IL8 R, interleukin 8 receptor; IL8, interleukin 8; iNOS, inducible nitric oxide synthasel;
IR, integrin receptor; JAK, janus kinase; JNK, cjun Nterminal kinase; LDLR, low density lipoproteinreceptor; MaIP, macrophage inflammatory protein; MAPK, mitogenactivated protein
kinase; MCP, monocyte chemoattractant protein; MDRP, multidrug resistance protein; MIP, migration inhibition protein; MMP, matrix metalloproteinase; NFκB, nuclear factor κlightchain
enhancer of activated B cells; NGF, nerve growth factor; NQO1, NAD(P)H: quinoneoxidoreductase 1; Nrf, nuclear factor 2related factor; ODC, ornithine decarboxylase; PAK, protamine
kinase; PCNA, proliferating cell nuclear antigen; PDGF, plateletderived growth factor; PhPD, phospholipase D; PKA, protein kinase A; PKB, protein kinase B; PKC, prorein kinase C; Pp60ctk,
pp60csrc tyrosine kinase; PPARγ, peroxisome preoliferatoractivated receptorγ; PTK, protein tyrosine kinase; Src2, Src homology 2 domaincontaining tyrosine phosphatase 2; STAT1,
signal transducers and activators of transcription 1; STAT3, signal transducers and activators of transcription 3; STAT4, signal transducers and activators of transcription 4; STAT5, signal
transducers and activators of transcription 5; TF, tissue factor; TGFβ1, transforming growth factorβ1; TMMP3, tissue inhibitor of metalloproteinase 3; TNFα, tumor necrosis factor α; uPA,
urokinasetype plasminogen activator; VCAM1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor; WTG1 , Wilmstumor gene 1.
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INTRODUCTION
This review focuses on curcumin, the compound that imparts the yellow
color to turmeric and that is used to flavor food. For centuries, turmeric
has been used as a remedy for multiple conditions including dyspepsia,
liver disorders, flatulence, jaundice, urinary tract diseases, colds, biliary
disorders, rheumatism, sinusitis, chronic otorrhea, diabetic ulcers, cough,
and various skin conditions (Hewlings & Kalman, 2017). Turmeric
possesses more than 300 different components, including phenolic
compounds and terpenoids (B. B. Aggarwal, Yuan, Li, & Gupta, 2013).
Turmeric contains three naturally occurring curcuminoids: Curcumin or
diferuloylmethane (75%), demethoxycurcumin (20%), and bisdemethox-
ycurcumin (5%; Akbik, Ghadiri, Chrzanowski, & Rohanizadeh, 2014).
Chemically, curcumin is a lipophilic molecule (1,7bis(4hydroxy3
methoxyphenyl)1,6heptadiene3,5dione) and a natural polyphenol. Its
chemical structure includes ketoenol tautomerism (depending on
whether curcumin resides in an acidic or alkaline medium). The molecule
rapidly permeates cell membranes and acts on multiple targets in various
cellular pathways to elicit various therapeutic actions in a variety of
diseases. Due to variable efficacy and the side effect profiles of many
modern medications, it is an appropriate time to assess the therapeutic
usefulness of ancient and traditional medications, including curcumin
(Kocaadam & Sanlier, 2017). Curcumins simple molecular structure,
along with its varied therapeutic effectsanditsuseinmanydisease
conditions has attracted much attention (Cheppudira et al., 2013;
Kunnumakkara et al., 2017). Curcumin can be used as an effective
treatment in several diseases by targeting different molecular targets and
with minimal toxicity to both humans and animals (Cheppudira et al.,
2013; Kocaadam & Sanlier, 2017; Kunnumakkara et al., 2017).
Curcumin is well known to exert therapeutic effects against a variety
of pathological conditions including cancer (Iranshahi et al., 2010;
Momtazi et al., 2016; Teymouri, Pirro, Johnston, & Sahebkar, 2017),
chemotherapyinduced adverse reactions (Mohajeri & Sahebkar, 2018;
Rezaee, Momtazi, Monemi, & Sahebkar,2017),metabolicsyndrome
(Panahi et al., 2015; Panahi, Khalili, Hosseini, Abbasinazari, & Sahebkar,
2014), osteoarthritis (Panahi, Rahimnia, et al., 2014; Sahebkar & Henrotin,
2016), dyslipidemias (Cicero et al., 2017; Ganjali et al., 2017; Sahebkar,
2014; Sahebkar et al., 2016; SimentalMendia et al., 2017), diabetes
(Hajavi et al., 2017; Panahi et al., 2017, 2018), nonalcoholic fatty liver
disease (Rahmani et al., 2016), endothelial dysfunction (Karimian, Pirro,
Johnston, Majeed, & Sahebkar, 2017), hyperuricemia (Panahi et al., 2016),
respiratory diseases (Lelli, Sahebkar, Johnston, & Pedone, 2017; Panahi,
Ghanei, Bashiri, Hajihashemi & Sahebkar, 2015; Panahi, Ghanei,
Hajhashemi & Sahebkar, 2016), and autoimmune diseases (Abdollahi,
Momtazi, Johnston, & Sahebkar, 2018; MomtaziBorojeni et al., 2018).
According to the literature, turmeric has been orally and topically used in
the prevention and treatment of skin diseases, which include parasitic
skin infections, infected wounds, premature aging, inflammation, and
psoriasis (Vaughn, Branum, & Sivamani, 2016).
Skin is the largest organ of the human body and is responsible for
covering, separating, and protecting the body from the external
environment, receiving sensory stimuli, and regulating body
temperature. Premature aging of the skin may be related to extrinsic
factors and personal lifestyle choice such as smoking, solar radiation
exposure, low air humidity, poor diet, and excess alcohol intake, as
well as systemic diseases such as diabetes mellitus. According to the
literature, curcumin possesses significant therapeutic effects for
various skin conditions, including antiinflammatory properties (B. B.
Aggarwal et al., 2013), ultraviolet (UV) protection (H. Li et al., 2016),
antioxidant effects (Xie et al., 2015), chemopreventive and che-
motherapeutic activity (Jiang, Jiang, Li, & Zheng, 2015; Lelli, Pedone,
& Sahebkar, 2017; Qiu et al., 2014; Toden et al., 2015), wound
healing benefits (Akbik et al., 2014), and antimicrobial effects (Krausz
et al., 2015). Due to its freeradical scavenging and antiinflammatory
properties, topical application of curcumin has allowed new
therapeutic avenues for wound healing, protection against oxidative
skin damage, skin cancer treatment (Qiu et al., 2014), control of pain
resulting from dermal burns (J. Kim et al., 2016; Mehrabani et al.,
2015), androgendependent skin disorders (Liao et al., 2001), and
decreasing skin irritation and reducing the symptoms of autoim-
munerelated skin disorders such as psoriasis (Kang et al., 2016).
However, recent studies have highlighted curcumins poor
bioavailability, low aqueous solubility, chemical instability, rapid
degradation, and rapid systemic elimination as major limitations for
its use in clinical practice (Kharat, Du, Zhang, & McClements, 2017).
This review aims to provide recent evidence for the usefulness of
curcumin in dermatology, as well as to suggest strategies to increase
its effectiveness and stability in vivo.
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ANTIOXIDANT
Exposure of human skin to solar radiation, chemical pollutants, and
mechanical stress results in the generation of free radicals. Free
radicals, like reactive oxygen species (ROS), are unstable chemical
entities that are highly reactive, cause skin damage through
inflammation, and may result in skin cancer. The resultant destruc-
tion of proteins, collagen, and elastic fibers is reflected in the signs of
skin aging (Poljsak & Dahmane, 2012). Antioxidants are compounds
that are protective by quenching free radical activity. The antioxidant
system in the skin includes superoxide dismutases (SOD), catalases,
and peroxidases (seleniumdependent glutathione peroxidases [GPx],
for example). Aging and prolonged exposure to ROSgenerating
factors, which include poor nutrition, alcohol intake, UV radiation,
stress, and environmental pollution, result in ROS accumulation,
which in turn damages the skin (Lee et al., 2013).
While most of the antioxidants have either a phenolic functional
group or adiketone group, there are different functional groups including
the Bdiketo group, carboncarbon double bonds, and phenyl rings
containing varying amounts of hydroxyl and methoxy entities that make
curcumin a unique and potent antioxidant. Curcumins antioxidant
activity is attributed to its diketone and phenol moieties (diferuloyl
methane portion of the molecule), which are free radical quenchers (Lee
et al., 2013). Masuda et al. (2001) proposed that the antioxidant
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PANAHI ET AL.
mechanism of curcumin includes an oxidative coupling reaction at the 3ʹ
position of the curcumin structure with lipid and a subsequent
intramolecular DielsAlder reaction. Curcumin functions as a mediator
in the regulation of genes related to the generation of proteins with
antioxidant characteristics such as heme oxygenase1, transcription and
growth factors, and inflammatory cytokines (Kou et al., 2013; OToole
et al., 2016). Curcumin also regulates antioxidant enzymes, scavenges
hyperglycemiainduced ROS, and profoundly increases the intracellular
antioxidant, reduced glutathione (GSH), which serves to decrease lipid
peroxidation. Studies have also shown strong protective effects of
curcumin against damage to the keratinocytes and fibroblasts in the skin
induced by H
2
O
2
(Phan, See, Lee, & Chan, 2001). Tetrahydrocurcumi-
noids obtained by hydrogenating cucuminoids (Prakash & Majeed, 2009)
are one of the major colorless metabolites of curcumin, in the form of its
glucuronide conjugate in bile. This conjugate compound has been shown
to have enhanced antioxidant properties with superior free radical
scavenging, free radical formation prevention, and increased lipid
peroxidation inhibition compared to curcumin and vitamin E (Prakash &
Majeed, 2009).
Therefore, the literature suggests that curcumin and its deriva-
tives may be promising and effective antioxidants that can be used
both orally and topically.
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ANTIINFLAMMATORY AND WOUND
HEALING
Acute and chronic inflammation are part of the bodys defense
mechanisms and involve immune cells, blood vessels, and molecular
mediators in response to harmful stimuli such as pathogens or
irritants. Pain, redness, immobility, swelling, and heat are the
hallmark signs of skin inflammation. Cytokines and hormonelike
polypeptide mediators like tumor necrosis factor α(TNFα, a key
proinflammatory cytokine) induce proinflammatory cytokines such as
interleukins 1, 6, 8, 10, and 21 and result in the activation of nuclear
factor κlightchainenhancer of activated B cells (NFκB), cJun
NH
2
terminal kinase, and mitogenactivated protein kinase (MAPK)
in the skin. These factors play a major role in the pathogenesis of
many inflammatory skin diseases and in the immunoregulatory
responses. Most inflammatory skin disorders are associated with
the overproduction of cytokines, dysregulation of cytokines, or
alterations in cytokine receptors (Figure 1).
Curcuminsantiinflammatory properties have been unequivocally
established (R. Agrawal, Sandhu, Sharma, & Kaur, 2015; Koop, de Freitas,
de Souza, Savi, & Silveira, 2015) in several different organs such liver and
skin through modulation of autoimmune disease and prevention of injury
to these organstissues (R. Agrawal et al., 2015). The primary mechanism
by which curcumin modulates inflammation is by reducing the expression
of the two main cytokines that are released by monocytes and
macrophages (Figure 1; Akbik et al., 2014; Kang et al., 2016). These
molecules are interleukin 1 (IL1) and TNFα, which have important roles
in the regulation of the inflammatory response. Also, curcumin inhibits
the activity of the proinflammatory transcriptional factor, NFκB, which is
responsible for the regulation of many genes involved during the initial
onset of the inflammatory response. A variety of kinases (AKT, PI3K, and
IKK) activate NFκB (Jagetia & Rajanikant, 2015). Suppression of NFκB
activation causes downregulation of cyclooxygenase2andinducible
nitric oxide synthase, and prevents upregulation of vascular endothelial
FIGURE 1 Activation of NFκB plays a
major role in the pathogenesis of many
inflammatory skin diseases. NFκB: nuclear
factor κlightchainenhancer of activated
B cells [Color figure can be viewed at
wileyonlinelibrary.com]
PANAHI ET AL.
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3
growth factor (VEGF) messenger RNA and microvascular angiogenesis
during inflammatory conditions. Curcuminsantiinflammatory actions
can be utilized to control inflammation of the skin resulting from different
skin diseases. For example, Arunraj et al. (2014) studied the anti
inflammatory actions of curcumin and curcumin nanospheres (CNSs) to
prevent denaturation of bovine serum albumin and compared it with
diclofenac sodium (a nonsteroidal antiinflammatory drug) both in vitro
and ex vivo. The results of in vitro stability testing for heattreated
albumin at physiological pH showed that CNSs had a greater anti
inflammatory effect in comparison with curcumin and diclofenac across a
dose range (251,000 μg/ml).
Skin is an essential protective organ for the body against the
environment. Chronic injuries in skin cause the body to initiate a
dynamic and multistep process of repair to regain tissue integrity. Four
processes are involved during the wound healing process: hemostasis,
inflammation, proliferation, and remodeling (Hussain, Thu, Ng, Khan, &
Katas, 2017; Margolis et al., 2011). At the initiation of the injury, rapid
aggregation of platelets via hemostasis causes clot formation. Migration
of neutrophils and macrophages to the wound site and release of
cytokines, thereby promoting fibroblast migration, results in inflamma-
tion at the wound site. Reepithelialization, generation of new blood
vessels (termed angiogenesis or neovascularization), and extracellular
matrix protein deposition by fibroblasts (collagen fibers, granulation
tissue, for example) occur to protect cell ingrowth. Collagen is used as
the building block during this proliferation phase (Hussain et al., 2017;
Margolis et al., 2011). The collagen remodeling and formation of scar
tissue is the final phase of wound healing. Inflammation, part of the acute
injury response, attracts neutrophils to the injured site resulting in the
release of inflammatory mediators such as TNFαand IL1(Arunrajetal.,
2014). Neutrophils in the wound area are associated with high levels of
destructive proteases and ROS molecules, which cause inflammation and
result in tissue damage, as well as prolonging the inflammatory phase.
The ROS molecules, bacterial infection, and protracted inflammation are
the major reasons for delays in wound healing (Guo & Dipietro, 2010;
Sorg, Tilkorn, Hager, Hauser, & Mirastschijski, 2017). Therefore,
curcumins potent antioxidant, antiinflammatory, and antiinfectious
actions can play a healing role in the process of wound resolution (Akbik
et al., 2014; Mohanty & Sahoo, 2017). Topical application of curcumin
has been shown to promote reepithelialization in burn wound areas to
increase the rate of wound healing (Kulac et al., 2013; LopezJornet,
CamachoAlonso, JimenezTorres, OrdunaDomingo, & GomezGarcia,
2011). Clinical studies have indicated an increased rate of epidermal
growth, increased thickness of the cuticular layer, and significant
improvement in wound healing in curcumintreated subjects when
compared to untreated subjects (Kulac et al., 2013; J. Li, Chen, & Kirsner,
2007; Wen, Wu, Chen, Yang, & Fu, 2012).
Kulac et al. (2013) reported that topical treatment with curcumin at a
concentration of 100 mg/kg body weight on burn wound healing in rats
enhanced the healing process compared to the control group, with a
decrease in inflammatory cells, and enhanced collagen deposition,
angiogenesis, granulation tissue formation, and epithelialization. Castan-
gia et al. (2014) used curcumin nanovesicles for wound healing in chronic
cutaneous pathologies in both in vivo and in vitro studies. They showed
that nanoentrapped curcumin prevented the formation of skin lesions
and inhibited the biochemical processes that normally lead to epithelial
damage. Based upon epidemiological evidence, they recommended the
daily topical application of curcuminloaded nanovesicles for patients at a
higher risk of skin wound infection to afford better protection. Using
liposomes and penetration enhancer-containing vesicles (PEVs) showed
an additional benefit by enhancing skin penetration. Krausz et al. (2015)
showed that topical use of curcuminencapsulated nanoparticles in an in
vivo murine wound model enhanced granulation tissue, reepithelializa-
tion and decreased wound area after 14 days of treatment leading to
improved wound healing. The results showed statistically significant
acceleration of wound healing in mice treated with curcuminencapsu-
lated nanoparticles (curcnp) compared to untreated, silver sulfadiazine,
coconut oil, control, control np, and curcumin (curc). Topical curcumin
used in breastfeeding women suffering lactationinduced mastitis showed
that curcumin effectively decreased mastitisrelated pain, breast tender-
ness, and erythema. This reduction in inflammation occurred within 72 hr
of administration without any side effects showing the efficacy of
curcumin in this situation (Afshariani, Farhadi, Ghaffarpasand, &
Roozbeh, 2014).
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PSORIASIS TREATMENT
Psoriasis is an epidermal hyperproliferative and autoimmune dermal
chronic inflammatory disease caused by genetic and immunologic
factors and normally affects the skin and joints (Lowes, SuarezFarinas,
& Krueger, 2014). Psoriasis shows triggering of intraregional
Tlymphocytes that prime basal stem keratinocytes to proliferate
excessively. Enhanced cell proliferation results in an excessive buildup
of cells on the surface of the skin and rapidly forms scales and red
patches that are itchy, inflamed, and sometimes painful. External
triggers like stress, alcohol, injury, infection, and medications may
initiate new psoriasis lesions. Psoriasis initiates from the premature
maturation of keratinocytes induced by an inflammatory cascade in the
dermis by dendritic cells, macrophages, and T cells. These immune cells
move from the dermis to the epidermis and secrete inflammatory
chemical signals (cytokines) such as IL 36γ,interferonγ(IFNγ), TNFα,
IL17, IL6, IL8, and IL22, that stimulate keratinocytes to proliferate.
Consequently, skin cells are replaced every 35 days rather than the
usual 2830 days, resulting in scales on the surface of skin.
Reports suggest that the antiinflammatory effect of curcumin
may allow it to act as an antipsoriasis agent (H. Liu, Danthi, &
Enyeart, 2006; Sun et al., 2017). Some reports on the inhibitory
activity of curcumin suggest that its action on the potassium
channel subtype Kv1.3 in T cells plays a central role in psoriasis
(Kang et al., 2016; H. Liu et al., 2006). Recently, Kang et al. (2016)
showed that generation of Tcell inflammatory factors, such as
IL17, IL22, IFNγ,IL2, IL8, and TNFα,decreasedby3060% in
mice with psoriasislike diseases after 20 days of oral curcumin.
Over 50% of Tcell proliferation was interrupted by application
of a 100μM curcumin preparation, and curcumin significantly
decreased the signs of psoriasis and improved the condition of the
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PANAHI ET AL.
skin. Curcumin (10 μM) reduced the generation of inflammatory
agents (IL17, IL22, IFNγ,IL2, IL8, and TNFα)invitroin
Tcellsby3060%. Sun et al. (2017) studied different formulations
of curcumin (dose: 0.25 mg·day
1
·mouse
1
) and tacrolimus (dose:
0.1 mg·day
1
·mouse
1
) on the imiquimod (IMQ)induced psoriasis
like mouse model both in vitro and in vivo, compared to a placebo
vehicle as control. Their results showed that treatment using
tacrolimus and 50 nm CurNPs gel reduced the white scale
thickness and the pink hue in inflamed skin. Also, they demon-
strated that encapsulation of curcumin into a poly(lacticco
glycolic) acid (PLGA)based nanoparticlecontaining hydrogel fa-
cilitated penetration through the skin and into the circulation (Sun
et al., 2017). In fact, this formulation had a superior performance
when compared to curcumin hydrogel in this imiquimod (IMQ)
induced psoriasislike mouse model, significantly improving the
antipsoriasis activity of curcumin.
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|
RADIATION PROTECTION
Solar radiation induces both an acute and chronic reaction in animal and
human skin. One of the most important agents causing ROS production in
the body is UVB irradiation, which causes oxidative modification of
cellular lipids, proteins, and nucleic acids and can lead to inflammation,
gene mutation, and immunosuppression (Dupont, Gomez, & Bilodeau,
2013; Natarajan, Ganju, Ramkumar, Grover, & Gokhale, 2014). High
levels of UV radiation kill most of the skin cells in the upper skin layer,
and cells that are not killed are damaged. In its mildest form, sunburn
leads to erythema on skin; however, severe sunburn may cause the skin
to blister and peel, which is not only painful but also leaves the new skin
unprotected and more prone to UV damage. Excessive UV radiation
damages the skins cellular DNA, producing genetic mutations that can
lead to precancers like actinic keratoses, and to skin cancers including
melanoma. UVB (290320 nm) radiation is highly mutagenic and
carcinogenic in animal experiments compared to UVA (320400 nm)
radiation.
Recently, several research groups have studied curcumins
protective effects against skin damage caused by chronic UVB
irradiation (Khandelwal et al., 2016). They showed that curcumin
exhibited photoprotective activity against acute UVB irradiation
induced photo damage. Topical application of curcumin before
chronic UV irradiation delayed the appearance of dermal tumors,
inflammation, and skin aging. H. Li et al. (2016) demonstrated that
shortterm topical application of emulsified curcumin (2 mg/ml
curcumin was prepared in 0.5% carboxymethyl cellulose sodium
[CMCNa]) protected against acute UVB irradiationinduced
inflammation and photoagingassociated damage in mouse skin
without any adverse effects. They show that curcumin attenuated
lactate dehydrogenase release induced by acute UVB irradiation in
HaCaT cells. The photoprotective effect of curcumin can be
attributed to its antioxidant properties and inhibition of UVB
induced oxidative damage by regulating the Nrf2 signaling path-
way in mouse skin and HaCaT cells (Khandelwal et al., 2016; H. Li
et al., 2016). Curcumin inhibited the generation of metallopro-
teases and NFκB in human dermal fibroblasts, which play a key
role in UVB exposureinduced skin damage.
Chopra et al. (2016) encapsulated curcumin with a biodegradable
polymer, PLGA (150 nm size range), and termed this formulation
preparation PLGACurNPs. They studied the protective effect of
curcumin in mouse fibroblasts (NIH3T3) and human keratinocytes
(HaCaT) against UV rays in vitro. They demonstrated sustained
release of curcumin at a low level from the PLGACurNPs and
suggested that this formulation could be an effective agent to protect
skin from exposure to UV irradiation. The results of this study
suggest that slow release of curcumin from PLGACurNPs could
counteract the adverse effects of photodegradation on curcumin
formulations upon exposure to UVA and UVB irradiation. UVB
exposure can induce cyclobutane pyrimidine dimers, leading to DNA
damage and skin cancer. According to various studies, considerable
DNA damage occurred with free curcumin, whereas this was not the
case with PLGACurNPs (Chopra et al., 2016).
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CANCER PREVENTION
Preclinical studies (Elad et al., 2013; H. Kim, Park, Tak, Bu, & Kim, 2014;
Kuttan, Sudheeran, & Josph, 1987; Phillips et al., 2013, 2011) on
curcumin have established its anticancer properties in breast, cervical,
skin, and pancreatic cell lines. However, rapid systemic clearance, low
aqueous solubility, poor physicochemical stability, and low cellular
uptake have limited the applications of curcumin. Recently, use of
nanotechnology for encapsulation of curcumin has improved its
therapeutic index, delivery, and bioavailability (Mangalathillam et al.,
2012). One of the most lethal skin cancers is melanoma, a result of
carcinogenic transformation of melanocytes (the pigmentcontaining
cells of the skin). The DNA damage caused by UV light exposure is
central to the development of melanoma in people with low levels of
skin pigment (Autier & Dore, 1998). Studies showed that cytokine
expression can support the growth and metastasis of melanoma cells.
Elias et al. reported that over 80% of human melanoma cell lines
produce excessive levels of several cytokines and growth factors, such
as transforming growth factor β(TGFβ), IL8, IL6, IL1α, VEGF, platelet
derived growth factorAA, and osteopontin (OPN), that are capable of
stimulating tumor growth, invasion, and angiogenesis.
Jiang et al. (2015) studied the human melanoma cell lines A375, MV3,
and M14 and the human normal lung fibroblast cell line MRC5invitro,
and showed that the viability of melanoma cells decreased with
increasing concentrations of curcumin from 5 to 50 μm. They demon-
strated that curcumin suppresses proliferation and induces double strand
break, suppressing the activation of NFκB (involved in tumor cell
proliferation) and causing apoptosis in melanocytes. Curcumin also
suppresses Bcell lymphoma protein 2 (Bcl2) and myeloid cell leukemia1
(Mcl1) expression and upregulates the expression of Bax (a p53), which
are primary drivers for apoptosis. Following curcumin treatment, the
tbax to Bcl2 ratio increased, demonstrating that curcumin induced
apoptosis. The regulation of Bax, Bcl2, and Mcl1 expressions indicates
PANAHI ET AL.
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5
that mitochondrial pathways play a key role in curcumininduced
apoptosis; thus, curcumin may provide antitumor efficacy and may offer
hope to those with melanoma. Additionally, Huang et al. (1997) showed
that topical application of very low doses (13,000 nM) of curcumin on
mouse epidermis inhibited the mean values of the 12Otetradecanoyl-
phorbol13acetateinduced epidermal oxidized DNA base 5hydroxy-
methyl29deoxyuridine and, hence, tumor promotion. Jose, Labala,
Ninave, Gade, and Venuganti (2018) studied the synergistic effect of
encapsulated curcumin in 1,2-dioleoyl-3-trimethylammonium-propane
(DOTAP)based cationic liposomes, as well as complexed with signal
transducers and activators of transcription 3 (STAT3) small interfering
RNA (siRNA); they demonstrated that in an animal model of melanoma
skin cancer, liposomal encapsulation of curcumin and STAT3siRNA
significantly inhibited tumor weight and volume progression when
compared with either liposomal curcumin or STAT3 siRNA alone.
Consequently, these data suggest that curcumin may inhibit skin cancer
and may provide adjuvant therapy without side effects in skin cancer
treatment.
7
|
ANTIAGING EFFECT
The in vivo study on male Wistar rats (Bala et al., 2006) showed that
curcumin can significantly decrease the normal agingrelated factors such
as lipid peroxidation, lipofuscin concentration, and intraneuronal lipofus-
cin accumulation, and enhance the enzymes SOD, GPx, and Na(+), K(+)
adenosine triphosphatase. Curcumin prevents premature aging of skin by
quenching free radicals and reducing inflammation, and has antiproli-
ferative properties through inhibition of NFkB, TNFα,andMAPK
pathway inhibition, as well as suppression of TGFβ(Tsai et al., 2012).
Curcumin also partially prevents UV damage that may decrease the
development of skin tumors and be an effective factor for prevention of
premature aging (Bala et al., 2006).
8
|
ANTIINFECTIVE PROPERTIES
Infectious diseases are a global issue and a wide range of synthetic
semisynthetic antibiotics have been developed for their treatment.
The development of multidrug resistant bacteria is an evolving health
problem and a major concern; hence, the need for new antibacterial
agents. The major drawbacks of many of these new drugs are their
expense, limited therapeutic window, mode of delivery, rapid
bacterial resistance and their side effects. Minimal or limited side
effects associated with natural products has led to an increasing
research focus to further investigate their use in this scenario.
Curcumins antimicrobial effects have been demonstrated in
several studies (Krausz et al., 2015; Luer, Troller, Jetter, Spaniol, &
Aebi, 2011). Krausz et al. (2015) studied the effect of curcnp as
antimicrobial agents on wound healing. According to this study, curc
np exhibited a significant antimicrobial effect against methicillin
resistant Staphylococcus aureus strain (MRSA) and Pseudomonas
aeruginosa (97.0% reduction of MRSA growth and 59.2% reduction
of P. aeruginosa growth by colony-forming unit (CFU) quantification)
from 8 hr onwards, in comparison to both untreated control and
control np (p0.0001). They showed that curcumin decreases the
bundling of FtsZ protofilaments (which are associated with binding
ability to the cellular proteins FtsZ32 and sortase A). As a result,
cytokinesis and cellular adhesion are interrupted, which also
interferes with the formation of a biofilm. Curcumins antibacterial
mechanisms involve suppression of bacterial cell proliferation due to
the inhibition of assembly dynamics of FtsZ (FtsZ polymerization) in
the Zring, which subsequently leads to interruption of prokaryotic
cell division. Also, Tortik, Steinbacher, Maisch, Spaeth, & Plaetzer
(2016) showed that curcumin has high photo killing efficiency against
microorganisms and a high photobleaching effect using a photo-
dynamic inactivation technique. This technique combines a harmless
visible light and a photosensitizer to kill pathogens through ROS
generation. Natural photoactive compounds, like curcumin, are cost
effective and provide excellent biocompatibility for most conceivable
applications. Consequently, the photosensitivity of human skin due to
prolonged exposure is decreased. According to several studies, it is
notable that the antibacterial effect of curcumin is greater against
Grampositive rather than Gramnegative species (due to less
interaction with Gramnegative bacterial cell membranes; Afshariani
et al., 2014; Bhawana, Basniwal, Buttar, Jain, & Jain N., 2011; Krausz
et al., 2015; Luer et al., 2011; Tortik et al., 2016). To increase the
antimicrobial effect of curcumin on Gramnegative species like
Escherichia coli, Tortik et al. (2016) added calcium chloride to increase
permeability of the Gramnegative bacterial cell membranes.
Curcumin can also work synergistically with antibiotics (Bhawana
et al., 2011; Mun et al., 2013), such as penicillin, ampicillin, oxacillin,
and norfloxacin, against the MRSA. Curcumins poor solubility in
water can be improved by the preparation of polyvinylpyrrolidone
curcumin (Tortik et al., 2016), which is efficacious against liquid
cultures of Grampositive S. aureus as well as Gramnegative E. coli
after in vitro permeabilization is enhanced with the inclusion of
CaCl
2
. Izui et al. (2016) studied the effect of curcumin against
homotypic and heterotypic biofilm formation. Their results showed
that curcumin prevented Porphyromonas gingivalis OMZ314 homo-
typic biofilm formation and that this effect was dosedependent,
inhibition surpassing 70% and 80% using 10 and 20 μg/ml of
curcumin, respectively. The effect of curcumin in preventing the
formation of heterotypic biofilm formation using P. gingivalis
OMZ314 and Streptococcus gordonii G9B showed curcumins inhibi-
tion of heterotypic biofilm formation was again dosedependent,
curcumin inhibiting biofilm formation by 55%, 80%, and 90% using
5, 10, and 20 μg/ml, respectively. Consequently, the antiinfective
properties of curcumin make it a promising natural agent for wound
healing, acne treatment and treatment of skin infections.
9
|
ACNE TREATMENT
Acne vulgaris is a longterm and cutaneous pleomorphic skin
disease of the pilosebaceous unit involving abnormalities in
6
|
PANAHI ET AL.
TABLE 1 Studies of curcumins effects in dermatological diseasesIn vivo
Condition
application Formulation Test model
Experimental
design
Duration of
exposure
treatment References
Photodamage
treatment
2 mg/ml curcumin in 0.5%
CMCNa (topical) 10 mM for the
treatment of HaCaT cells
Hairless mice and HaCaT
cells
In vivo, in vitro 14
days; 24 hr
Curcumin is an active agent for
preventing and treating UV radiation
induced acute inflammation and
photoaging due to antioxidant defenses
and inhibition of oxidative damages via
regulating Nrf2 signaling pathway
H. Li et al. (2016)
1030 μM curcumin Human foreskin (human
dermal fibroblasts)
In vitro 24 hr Curcumin inhibit the UVBinduced
expression of MMPs and blocks ROS
production and the MAPK/NFjB/AP1
signalling pathway in human dermal
fibroblasts (HDFs). Therefore, an
effective therapeutic candidate for
preventing and treating of skin
photoageing
Phillips et al. (2013)
10 μmol/L curcumin Murine epidermal In vitro 24 hr Prevent UVBinduced both mTOR and
FGFR2 signaling potentially leading to
a new therapeutic candidate for
advanced cancer with dual pathway
dysregulation
Khandelwal
et al. (2016)
Skin cancer
treatment
25 μM curcumin Melanoma cell culture In vitro 24 hr Curcumininduced melanoma cell
death by associated with mPTP
opening
Qiu et al. (2014)
15 mg/100 µl (topical and oral) SKH1 hairless mice In vivo Curcumin inhibits UV radiation
induced skin cancer and prolong time
to tumor onset
Phillips et al. (2013)
0.02% wt/wt (oral) Mouse In vivo 114 weeks Curcumin present high
anticarcinogenic activity in skin
cancer through the inhibition of IGF1
signaling
H. Kim et al. (2014)
5 and 15 mg/day (oral) SCID mice In vivo 24 days Curcumin inhibit skin squamous cell
carcinoma growth and blocks tumor
progression by inhibiting pS6 and
mTOR pathway
Phillips et al. (2011)
0.11.0 mg/ml CCNGs Human melanoma cell,
human dermal fibroblast,
and porcine skin
In vitro 624 hr Effective transdermal penetration of
CCNGs could leading to specific
advantage for the treatment of
melanoma
Mangalathillam
et al. (2012)
Curcumin nanoniosome gel
(3.15 ± 0.086 drug loading;
topical)
Swiss albino mice In vivo 7 weeks Effective transdermal penetration of
curcumin nanoniosome significantly
inhibit proliferation of squamous cell
carcinoma in DMBAtreated animals
R. Agrawal
et al. (2015)
(Continues)
PANAHI ET AL.
|
7
TABLE 1 (Continued)
Condition
application Formulation Test model
Experimental
design
Duration of
exposure
treatment References
Antimicrobial 0.00030.0004 g/L curcumin
loaded nanocubosomal hydrogel
Escherichia coli In vitro 24 hr Enhance bioavailability of curcumin
able to increase curcumin
antibacterial activity in topical drug
delivery
Arunraj
et al. (2014)
50 or 100 μM curcuminbound to
polyvinylpyrrolidone
Staphylococcus aureus,E. coli Ex vivo
(porcine skin
model)
24 hr Increase water solubility of curcumin
and highly efficient against S. aureus
an antibacterial against E. coli
Tortik et al. (2016)
510 mg/ml curcumin
encapsulated nanoparticles
Pseudomonas aeruginosa,
methicillinresistant S.
aureus strain
In vitro 24 hr Inhibit growth of Grampositive and
Gramnegative organisms
Krausz et al. (2015)
100400 μg/ml curcumin
nanoparticles
S. aureus, Bacillus subtilis, E.
coli, P. aeruginosa,
Penicillium chrysogenum,
Aspergillus niger
In vitro 24 hr Higher aqueous solubility and more
effective antimicrobial activity of
curcumin nanoparticle compare to
curcumin
Bhawana
et al. (2011)
7250 μg/ml curcumin S. aureus In vitro 24 hr Curcumin has synergistic effect in
combination with antibiotics
Mun et al. (2013)
Wound healing 2 g/L curcumin in chloroform
including dissolved
polyvinylpyrrolidone and ethyl
cellulose (topical)
Rat In vivo 21 days A combination of polyvinylpyrrolidone
and ethyl cellulose significantly
improve the permeation of curcumin
transdermal patch leading to
acceleration of wound healing and
repair
Gadekar, Saurabh,
Thakur, and
Saurabh (2012)
Curcumin cream (200 mg per
pump; topical)
Breastfeeding women with
lactational mastitis
Clinical 72 hr Topical application of curcumin
significantly decrease the signs of
lactational mastitis such as pain,
breast tension, and erythema
Afshariani
et al. (2014)
2% concentration curcumin
ointment (topical)
Rat In vivo 21 days A decrease in size of the burn wounds
and a reduction in inflammation after
14th day
Mehrabani
et al. (2015)
200 mg/cm
2
of curcumin (topical) Minipig In vivo 35 days Reduce expression of cyclooxygenase
2 and NFkB, and decrease the
epithelial desquamation lead to
stimulation of wound healing
J. Kim et al. (2016)
10 mg/ml quercetin and curcumin
loaded phospholipid liposome
nanovesicles (topical)
Newborn pig skin, mice In vitro, in vivo 1 day,
4 days
Increase drug bioavailability and
prevent the formation of skin lesion
Castangia
et al. (2014)
100 mg/kg body weight (topical) Wistaralbino rats In vivo 12 days Rise in the hydroxyproline levels and
expression of PCNA in skin
tissuesbytopical application of
curcumin leading much faster wound
healing
LopezJornet
et al. (2011)
(Continues)
8
|
PANAHI ET AL.
TABLE 1 (Continued)
Condition
application Formulation Test model
Experimental
design
Duration of
exposure
treatment References
Encapsulated curcumin loaded in
polymeric micelles in thermo
sensitive hydrogel composite
(topical)
SpragueDawley albino rat In vivo 7 days Very good wound healing activity
present in both linear incision and
fullthickness excision wound model
in rats
Krausz et al. (2015)
Curcuminloaded hydrogel of
xanthan and galactomannan
(topical)
Rat In vitro, in vivo 12 hr,
21 days
Curcumin loaded into xanthan
galactomannan hydrogels present
good skin permeation and topical
inflammation inhabitor
Koop et al. (2015)
Anti
inflammation
2 g/L of curcuminloaded vesicular
system (topical)
Female Laca mice and male
Wistar rats
Ex vivo, in vitro 24 hr Improve the skin permeability of
curcumin and bioavailability leading
to significant inflammatory
inhabitation.
R. Agrawal
et al. (2015)
0.145% wt/wt nanocurcumin gel
(topical)
Wistar rat In vivo 12 days High shelf life and effective anti
inflammatory
AlRohaimi (2015)
Psoriasis
treatment
40 mg/kg curcumin (oral) Mice In vivo 20 days Depress expression of cytokines and
Tcell proliferation though Kv1.3
channelinhabitation lead to a great
therapeuticeffect without obvious
side effects.
Kang et al. (2016)
Tablets containing 100 mg of
standardized Curcuma longa
extract with 12 mg of curcumin
per tablet (oral)
Patient male and female Clinical 75 days Combination of the oral curcuma
extract and UVA or visible light
irradiation improve treatment rate of
moderatetosevere plaque psoriasis
CarrionGutierrez
et al. (2015)
10 μM of curcumin (oral) Mouse In vivo 20 days Significantly inhibited secretion of
inflammatory factors including
interleukins, TNFαin T cells and a
great potential to treat psoriasis
without toxicity to kidney
Kang et al. (2016)
Encapsulation of curcumin in poly
(lacticcoglycolic acid)
nanoparticles (topical)
Mice In vivo 7 days Significantly increase curcumin
dispersion, sustainedrelease,
accumulation, skin penetration and
entrance the blood circulation, which
improves antipsoriasis activity
Sun et al. (2017)
(Continues)
PANAHI ET AL.
|
9
sebum production that occurs when hair follicles are clogged with
dead skin cells and oil from the skin. Five important factors in the
pathophysiology of acne generation are (a) excess sebum
secretion from sebaceous glands, (b) bacterial infection (Propio-
nibacterium acnes), (c) follicular epidermal hyperproliferation, (d)
inflammation, and (e) genetics (Beylot et al., 2014; Williams,
Dellavalle, & Garner, 2012). Different gene candidates have been
proposed, including certain variations in TNFα,IL1α,and
CYP1A1 genes, among others. Acne can create either nonin-
flammatory or inflammatory lesions, mostly affecting the face but
also the back and chest. Although the use of antibiotics is a
currently acceptable method to treat acne, the side effects of
antibiotics and development of antibiotic resistance in Staphylo-
coccus epidermidis demonstrates the need for nontraditional
antimicrobial agents in the treatment of acne vulgaris.
Curcumins antiinflammatory and antimicrobial properties make
it an ideal candidate for acne treatment. C. H. Liu & Huang (2012)
developed a curcuminloaded myristic acid microemulsion which was
shown to be an excellent vehicle for delivering curcumin and
inhibiting S. epidermidis (a bacteria involved in acne). Thus, curcumin
is a promising therapeutic agent for the topical treatment of acne
vulgaris. Also, in other studies by C. H. Liu & Huang (2013)), an
emulsion of curcuminloaded lauric acid lipid vehicles showed
antibacterial activity against propionibacteria species (the primary
agent involved in inflammatory acne). The effectiveness of this
emulsion was considerably increased by the nanosized vehicle due to
enhanced effective contact with the bacteria and increased cell
membrane penetration.
10
|
CURCUMIN ANALOGUES
In spite of these numerous advantages, the limitations to the use of
curcumin, which include bioavailability challenges, low stability, low
skin penetration, limited water solubility, and instability following
exposure to light in the UVvisible range, has meant that this
bioactive compound has found limited use as a pharmaceutical
ingredient (Jafari, Sabahi, & Rahaie, 2016; Liang, Friedman, &
Nacharaju, 2017). Notably, reports (Arunraj et al., 2014) have
shown that curcumins antioxidant and antiinflammatory proper-
ties are not only decreased following light exposure but, in
addition, it can induce oxidative stress, apoptosisnecrosis, cell
injury, and cell death. In fact, the phototoxic and photosensitizing
effects of crude curcumin are controversial. According to the
literature (Mondal, Ghosh, & Moulik, 2016), the absorption spectra
of curcumin falls in the UVvisible range, indicating its photo-
degradability. Additionally, poor bioavailability of curcumin (W. Liu
et al., 2016; Prasad, Tyagi, & Aggarwal, 2014) makes it a class II
drug in the biopharmaceutics classification system. In the last
couple of decades, nanotechnology has been used to increase the
stability of drugs, decrease side effects, and improve their delivery
(Arunraj et al., 2014; Rachmawati, Budiputra, & Mauludin, 2015).
Recently, to overcome some of the limitations of curcumin,
TABLE 1 (Continued)
Condition
application Formulation Test model
Experimental
design
Duration of
exposure
treatment References
Acne treatment 0.43 µg/ml of Curcumin Pig skin In vitro 24 hr Combined curcuminlauric acid in the
nanosized vehicles significantly inhibit
the growth of Propionibacterium acnes
and present a treatment of acne
vulgaris
C. H. Liu and
Huang (2013)
100 mg/kg curcumin (oral) Mouse In vivo 20 days Significant raise the glutathione
concentration and activities of GPx
and SOD enzymes in skin, whereas
lipid peroxidation declined
significantly meaning to antioxidant
status of Curcumin
Jagetia and
Rajanikant (2015)
Note.AP1: activating protein 1; CCNG: curcuminloaded chitinnanogel; DMBA: 7,12Dimethylbenz[a]anthracene; FGFR2: Fibroblast growth factor receptor 2; GPx: glutathione peroxidase; IGF1: Insulinlike
growth factor 1; MAPK: mitogenactivated protein kinase; mPTP: 1methyl4phenyl1,2,3,6tetrahydropyridine; mTOR: mammalian target of rapamycin; NFkB: nuclear factor κlightchainenhancer of
activated B cells; PCNA: proliferating cell nuclear antigen; ROS: reactive oxygen species; SOD: superoxide dismutase; TNFα: tumor necrosis factor α; UVB: ultraviolet B.
10
|
PANAHI ET AL.
different curcumin encapsulated formulations on a nanosize
and microsize scale, including liposomesphospholipid (Manconi
et al., 2017), nanogels (Mangalathillam et al., 2012), monooleine
aqueous dispersion (Puglia et al., 2013), nanostructured lipid
carriers (Chanburee & Tiyaboonchai, 2017), nanoemulsions (Kumar
et al., 2016), polymeric micelles (M. Li et al., 2016) and polymeric
nanoparticles (Yin, Zhang, Wu, Huang, & Chen, 2013), elastic
vesicular systems (R. Agrawal et al., 2015), and lamellar and
hexagonal mesophases (FonsecaSantos, Dos Santos, Rodero,
Gremiao, & Chorilli, 2016) have been investigated and have
demonstrated improved aqueous solubility, bioavailability, and
increased targeting potential. Additionally, continuous, lowlevel
release of curcumin from encapsulated formulations should protect
encapsulated compounds (including curcumin) from airinduced
oxidation and may afford longterm activity and stability. As an
example, AlRohaimi (2015) has shown that the permeation rate,
drug release parameters, shelflife, and antiinflammatory activity
of curcumin noticeably improved by using amorphous NanoCur as
the source of curcumin, which was then incorporated into a
nanoemulsion (o/w) using a water titration method and subse-
quently evaluated for topical drug delivery. Also, some research
groups (Jeengar, Rompicharla, et al., 2016; Jeengar, Shrivastava,
Mouli Veeravalli, Naidu, & Sistla, 2016) have introduced the use of
emu oil as a carrier for topical curcumin application due to
increased solubility and improved skin penetration, resulting in a
synergistic antiinflammatory effect. It should, however, be noted
that the use of emu oil as an antiinflammatory agent is
controversial. On the other hand, ethanol, dimethyl sulfoxide, and
propylene glycol were used as solvents for curcumin in aqueous
formulations such as curcumin gels. Menthol has been proposed as
a penetration enhancing agent in preparations of curcumin gels for
topical application due to enhanced percutaneous flux and
transdermal absorption of curcumin (Patel, Patel, & Patel, 2009).
Also, some polymers, such as carbopol, hydroxypropyl methylcel-
lulose, and sodium alginate have been introduced into formulations
to serve as gelling agents and have shown enhanced bioavailability
and dermal permeation of curcumin (Patel et al., 2009).
11
|
CONCLUSION
Curcumin exhibits a variety of important properties and holds
promise for the treatment of dermatological diseases as summarized
in Table 1. Recently, clinical research and preclinical scientific studies
have demonstrated curcumins remarkable antioxidant, antiinflam-
matory, and antibacterial activities, which can be effectively
utilized to treat acne, psoriasis, dermal wounds, sun burn, premature
aging, melanoma, and ROS agglomeration.
Finally, it would appear that the limitations of poor bioavailability
and low stability of curcumin can be overcome using nanotechnology,
including liposomesphospholipid, nanogels, nanostructured lipid
carriers, nanoemulsions, polymeric micelles, and various polymeric
nanoparticulate methods, though further studies are needed to
clarify the utility of curcumin.
ACKNOWLEDGMENT
The authors are thankful to the Clinical Research Development Unit
of the Baqiyatallah Hospital (Tehran, Iran).
CONFLICT OF INTERESTS
Muhammed Majeed is the Founder and Chairman of Sabinsa
Corporation and Sami Labs Limited. For remaining authors, there
are no conflicts of interest.
ORCID
Stephen L. Atkin http://orcid.org/0000-0002-5887-7257
Amirhossein Sahebkar http://orcid.org/0000-0002-8656-1444
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How to cite this article: Panahi Y, Fazlolahzadeh O, Atkin SL,
et al. Evidence of curcumin and curcumin analogue effects in
skin diseases: A narrative review. J Cell Physiol. 2018;114.
https://doi.org/10.1002/jcp.27096
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... 46 Curcumin Curcumin originates from turmeric or Curcuma longa and belongs to the family of Zingiberaceae or ginger that is usually used as spice for food flavouring. 49,50 Turmeric is commonly-used in South Asia, India, and Indonesia and is often used as a dye or food color since it exists in bright orange-yellow crystals. 51 According to Panahi et al 49 turmeric contains curcuminoids which include curcumin or specifically, deferuloymethane (75%), demethoxycurcumin (20%), and bisdemethoxycurcumin (5%). ...
... It is a keto-enol tautomer and is a natural polyphenol that have many important uses. 49 Additionally, curcumin is used in the treatment of several diseases since the molecule rapidly penetrates the cell membranes and acts on multiple targets in different-cellular pathways. Some studies reported that curcumin is 1) a useful antimicrobial agent, 2) a preservative, and 3) possesses different therapeutic actions against cancer, dyslipidemia, skin diseases, osteoarthritis, diabetes, metabolic syndrome, endothelial dysfunction, autoimmune disease, non-alcoholic fatty liver disease, respiratory disease, depression, premenstrual syndrome, and hyperuricemia. ...
... Some studies reported that curcumin is 1) a useful antimicrobial agent, 2) a preservative, and 3) possesses different therapeutic actions against cancer, dyslipidemia, skin diseases, osteoarthritis, diabetes, metabolic syndrome, endothelial dysfunction, autoimmune disease, non-alcoholic fatty liver disease, respiratory disease, depression, premenstrual syndrome, and hyperuricemia. 49,51 Since curcumin has antioxidant and anti-inflammatory properties, it can be used to treat skin disorders. Panahi et al 49 reported that curcumin has minimal toxicity to humans and animals, while Patel et al 51 stated that, except for gastrointestinal distress, no major toxicity occurs upon oral administration of curcumin. ...
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The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.
... CUR has been shown to modulate signal transducers and transcription activators like JAK-STAT, Nrf2, Notch-1 and nuclear factor kappa B (NF-kB) as well as the protein kinases Akt and MAPK [16,17]. The anti-inflammatory effects of CUR are used to target and control skin inflammation in different skin diseases; its mechanism of action involves reducing the expression of cytokines released by immune cells [18]. ...
... Studies on mechanisms involved on the inhibition activity of CUR suggested a targeted action on the potassium channels of immune cells, which have a central role in chronic immune pathologies such as psoriasis [58]. For this reason, it has been suggested that CUR may be considered antipsoriatic due to these anti-inflammatory effects [18,20]. ...
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... Nevertheless, there are a vast number of studies conducted with curcumin to investigate anti-inflammatory, antioxidant, anti-carcinogenic, antiviral, and anti-infection activities. Owing to its antibacterial, antioxidant, anti-inflammatory, and antiseptic properties, curcumin has been proven useful in treating several skin diseases, such as psoriasis, infection, acne, skin inflammation, and skin cancer [180] . Curcumin controlled the in vitro growth of Staphylococcus aureus and Pseudomonas aeruginosa in an in vivo murine wound model, and topical administration accelerated healing [181] . ...
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... There is no consensus on the definition of the best concentration of curcumin for topical treatments of skin diseases, with concentrations of curcumin ranging generally from 1% to 2% (w/w) in topical formulations. In this sense, in the research effort entertained herein, biopolysaccharide gels were produced integrating 1.0, 1.5 and 2.0% (w/w) of pure curcumin (Kim and Lio, 2020;Panahi et al., 2019;Vollono et al., 2019). The pharmaceutical form ''gel" was therefore used to evaluate the effectiveness of CAGE-IL in enhancing the delivery of curcumin via the transdermal route. ...
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Curcumin, the bioactive component of turmeric, has been used for the treatment of several diseases including diabetes and its complications. Curcumin has been shown to exert pleiotropic effects by modulating different signaling molecules, including transcription factors, chemokines, cytokines, and adipokines. Disturbed regulation of adipokines, which include adiponectin, leptin, resistin, and visfatin, are implicated in the development of insulin resistance and Type 2 Diabetes. Here, we review the findings of in vitro, in vivo, and clinical studies on the modulating effects that curcumin treatment exerts on adipokines. Additionally, we examine the potential beneficial effects of the activity of curcumin in the prevention and treatment of diabetes and its comorbidities.
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