Review Article

Skin Pharmacology
and Physiology Received: May 10, 2023
Skin Pharmacol Physiol 2023;36:235–248
Accepted: October 27, 2023
DOI: 10.1159/000535100 Published online: November 26, 2023

Clinical Studies on Topical Curcumin

Ritamaria Di Lorenzo a Federica Forgione a Antonietta Bernardi b
Antonia Sacchi a Sonia Laneri a Giovanni Greco a
a
Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, Naples, Italy; bNeatique Srl, Developing

Downloaded from [Link] by guest on 30 December 2024

and Consulting Service Agency, Naples, Italy

Keywords Introduction
Curcumin · Turmeric · Curcuma longa · Topical application ·
Skin diseases · Skin health · Dermatology · Cosmeceuticals · Curcumin is one of the most frequently employed
Nutricosmetics natural components of nutraceutical products. It is also
increasingly being used in cosmeceutical formulations
although its intense yellow-orange color is an unwelcome
Abstract feature [1]. The recognized reputation of curcumin in
Background: Curcumin is a polyphenolic compound these two markets can be mainly ascribed to its antiox-
present in turmeric (Curcuma longa). Curcumin, turmeric idant, anti-inflammatory, and antimicrobial properties
powder, and extracts are widely used in traditional Indian [2] combined with an excellent safety profile [3].
medicine and are active ingredients of dietary supple- Oral usage of curcumin is complicated by poor bio-
ments and cosmeceutical products. The pharmacological availability due to an extremely low water solubility, a
properties of curcumin/turmeric as well as the studies high chemical reactivity with water and oxygen, and a
performed in vitro, in animal models, and in volunteers first-pass effect [4]. To circumvent this problem, several
have been the objects of a vast literature. Most of the technological approaches have been devised [5]. Efforts
clinical studies report on the effects of curcumin/turmeric have likewise been made to optimize its topical
administered orally, while only a few describe its topical delivery [6].
applications. Summary: This review focuses on clinical Curcumin can be used either as a single ingredient or
studies in which curcumin/turmeric was applied topically as the main component of extracts obtained from the
to treat various skin conditions based on its antioxidant, rhizome of Curcuma longa (turmeric). The complex
anti-inflammatory, and antimicrobial properties. pharmacology of curcumin encompasses at least the
Key Messages: The clinical studies employing curcumin/ following activities: antioxidant, anti-inflammatory, an-
turmeric as the only active ingredient allow us to ap- timicrobial, anticancer, neuroprotective, cardiovascular,
preciate its therapeutic potential without confounding and metabolic disease preventing [7]. Such a peculiar
contributions coming from additional pharmacologically pharmacological profile results from a multitude of
active substances present in the same formulation. biochemical targets hit by curcumin, including tran-
Curcumin/turmeric was regarded as an attractive alter- scription and growth factors, protein kinases, enzymes,
native to conventional drugs, such as corticosteroids and cytokines, and others [8].
antibiotics, thanks to its characteristics of a safe and well- Most of the clinical studies concerning curcumin/
tolerated natural substance. © 2023 S. Karger AG, Basel turmeric refer to oral administration, while only a few

karger@[Link] © 2023 S. Karger AG, Basel Correspondence to:

[Link]/spp Sonia Laneri, slaneri @ [Link]
Giovanni Greco, ggreco @ [Link]
 Table 1. Clinical trials reporting efficacy assessment of curcumin or turmeric for topical treatment

236
No. Intervention and dosage (w/w) Skin condition Trial Type of Statistical Reference
design outcome significance
of results

1 1% curcumin Psoriasis OL, Clinical, Yes Heng et al. [10] (2000)

AC, NTC instrumental
2 Turmeric (ns) Psoriasis R, DB, PC Clinical Yes Sarafian et al. [11] (2015)
3 Turmeric (ns) Scalp psoriasis R, DB, PC Clinical Yes Bahraini et al. [12] (2018)
4 12% curcumin Hypertrophic scarring CR Clinical No Heng et al. [13] (2011)
5 Turmeric (ns) Vitiligo R, DB, PC Clinical Yes Jalalmanesh et al. [14] (2022)
6 200 mg curcumin per pump Lactational mastitis R, DB, PC Clinical Yes Afshariani et al. [15] (2014)
7 0.5% curcumin Skin and mucosae NC Clinical Yes Kuttan et al. [16] (1987)
cancerous lesions
8 4% curcumin Radiodermatitis R, PB, Clinical No Ryan Wolf et al. [17] (2020)

DOI: 10.1159/000535100
PC, AC
9 5% C. longa Androgenetic R, DB, Clinical No Pumthong et al. [18] (2012)
alopecia PC, AC
10 Turmeric (ns), sandalwood oil (ns) Radiodermatitis R, OL, PC Clinical Yes Palatti et al. [19] (2014)
11 0.1% curcumin, 0.1% piperine, 0.03% capsaicin Alopecia areata R, OL, AC Clinical, Yes Mao et al. [20] (2022)

Skin Pharmacol Physiol 2023;36:235–248

instrumental
12 Turmeric (ns), neem (ns) Scabies NC Clinical No Charles et al. [21] (1992)
13 Turmeric (ns), A. indica (ns), C. tora (ns) Tinea corporis R, SB, PC Clinical, Yes R et al. [22] (2022)
instrumental
14 0.5% turmeric, 10% henna Capecitabine- R, TB, PC Clinical No Elyasi et al. [23] (2022)
related HFS
15 Turmeric (ns), C. gigantea (ns), P. glabra (ns), S. Eczema NC Clinical Yes Rawal et al. [24] (2009)
xanthocarpum (ns), C. camphora (ns), J. regia (ns)
16 Turmeric (ns), A. barbadensis (ns), A. indica (ns), H. Acne R, DB, PC Clinical Yes Lalla et al. [25] (2001)
indicus (ns), T. chebula (ns), T. arjuna (ns), W.
somnifera (ns)
17 16.0% turmeric, 0.1% turmeric oil, 8.0% S. album, Pruritus R, OL, AC Clinical No Chatterjee et al. [26] (2005)
3.0% L. inermis, 3.0% O. sanctum, 0.5% G. glabra,
0.5% V. zizanioides, 0.5% surasar, 0.1% A. moschatus,
0.025% C. sativus, 0.00032% Swarna Bhasma
18 C. zedoaria (ns), A. membranaceus (ns), S. pharbitidis MPE R, DB, PC Clinical, No Freize et al. [27] (2017)
(ns), cassia twig (ns), P. arecae (ns), borneol (ns) instrumental

Laneri/Greco
19 0.02% curcumin, 1.0% tocopheryl acetate, 1.0% Skin aging R, DB, PC Clinical, Yes Di Lorenzo et al. [28] (2022)
acerola fruit, 0.5% selenomethionine (calcium instrumental
phosphate)

AC, active-controlled; CR, case report; DB, double-blind; NC, non-comparative; NTC, no-treatment-controlled; ns, not specified, OL, open label; PB, partially blind;
PC, placebo-controlled; R, randomized; SB, single-blind; TB, triple-blind.

Di Lorenzo/Forgione/Bernardi/Sacchi/
Downloaded from [Link] by guest on 30 December 2024
report its topical applications. After a brief recall of the as a yellow-orange crystal powder. Its hydrophobic
chemical and physical properties of curcumin and cur- character (estimated logP = 3.2 [32, 33]) and high melting
cuminoids, this review covers the most significant clinical point (183°C [34]), this latter related to a high lattice
studies in which curcumin (alone or as the principal energy, are consistent with an extremely low solubility in
component of turmeric extracts) was applied topically to water (less than 10 mg dissolves in 1 mL [35, 36]).
relieve symptoms of skin diseases or to improve skin Curcumin exists in the solid state as a keto-enol
health care. Compared with a review by Vaughn et al. [9] tautomer (4, Fig. 2) characterized by an intramolecular
discussing the effects of orally and topically administered hydrogen bond, whereas in aqueous solutions it pre-
curcumin/turmeric on skin health, this article represents dominates as diketo form (1, Fig. 1) with intermolecular
an update as it includes additional works, most of which hydrogen bonds engaged between the two carbonyl ox-
published after 2015. ygens and water [37]. In aqueous solutions, it behaves as a
A special attention has been given to investigations triprotic weak acid with pKa1, pKa2, and pKa3 values of
where curcumin/turmeric was employed as a single active 7.8, 8.5, and 9.0, the former related to the enol hydrogen
ingredient. We have also summarized clinical studies of the keto-enol tautomer and the remaining ones to the
employing curcumin/turmeric in combination with other two phenol hydroxyls [38]. Curcumin can be easily

Downloaded from [Link] by guest on 30 December 2024

active constituents in the same topical formulation al- dissolved in acetone and is sparingly soluble in
though such studies do not permit to single out the ethanol [39].
specific effects exerted by curcumin/turmeric. The main As mentioned, the clinical use of curcumin is ham-
features of the clinical studies discussed in the present pered not only by low solubility in water but also by poor
paper are listed in Table 1. chemical stability [40, 41]. In fact, it rapidly degrades in
aqueous solutions with a pH above 3 through hydrolysis
[42] and autoxidation [43]. However, the speed of these
Curcuminoids: Sources, Chemical, and Physical reactions is much slower in non-aqueous solvents (e.g.,
Properties ethanol, isopropanol) and reasonable stability can also be
obtained in 10–20% w/v ethanol aqueous solutions [40].
Turmeric is the common name of C. longa, a flowering The incorporation of curcumin into oil-in-water emul-
plant belonging to the ginger family (Zingiberaceae) sions has been found to improve its water dispersibility
cultivated in India and Southeast Asia. The rhizomes of and chemical stability [41].
this plant are dried and ground to yield a yellow-orange
powder used as a spice or a dye. Solid and liquid extracts
of turmeric are the active ingredients of dietary supple- Curcumin or Turmeric as a Single Ingredient
ments and topical products in the form of gels, creams, or
ointments. In this section, the discussion focuses on nine studies
Turmeric contains several chemically related com- (#1–9 in Table 1) in which curcumin or turmeric was
pounds, known as curcuminoids, in concentrations used as the only active ingredient in topical formulations
varying from 3% to 5% w/w [29]. The most abundant and used to treat various skin diseases.
biologically active curcuminoids are curcumin (1), de-
methoxycurcumin (2), and bisdemethoxycurcumin (3) Curcumin and Turmeric to Treat Psoriasis
(structures in Fig. 1) present in crude extracts in relative Psoriasis, an inflammatory disease characterized by an
amounts (w/w) of 60–70%, 20–27%, and 10–15%, re- abnormal proliferation of epidermal cells [44], has been
spectively [30]. Since curcuminoids display similar bio- associated with overactivity of phosphorylase kinase
logical activities, curcumin, curcuminoids, and curcumin (PhK) [45]. PhK is a regulatory protein kinase that
extracts are often employed as synonyms in literature. stimulates glycogen breakdown. It receives input from
Although curcumin can be synthesized [31], its hormonal and neuronal signals transmitted through
industrial-scale production is based on extraction the second messengers Ca2+ and cAMP and responds
methods from turmeric. Good quality dry extracts of by phosphorylating and thus activating glycogen
turmeric are commercially available which contain up to phosphorylase [46].
95% w/w of curcuminoids. The evidence that curcumin is a selective non-
Curcumin belongs to the chemical class of polyphe- competitive inhibitor of PhK [47] was the rationale of
nols. It is a symmetric molecule incorporating two fer- an open-label (OL) clinical study which tested the hy-
uloyl moieties separated by a methylene linker. It appears pothesis that the anti-psoriatic property of curcumin is

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 237

Studies DOI: 10.1159/000535100
linked to its capability of counteracting the PhK effects in the vehicle might have contributed to a small extent to the
the skin [10]. Thus, PhK activity was measured in the skin beneficial effects of the two gels.
of 40 subjects (four groups of 10). The first 2 groups were Bahraini et al. [12] evaluated the clinical efficacy of
psoriatic patients treated for 4 weeks with 1% curcumin turmeric in mitigating the symptoms of mild-to-
(alcoholic gel) or 0.005% calcipotriol (a vitamin D3 an- moderate psoriasis. This randomized, DB, PC trial in-
alogue); the third group of untreated patients with volved 30 volunteers. The patients were equally divided
psoriasis was the control; the fourth group consisted of into two groups: one receiving a turmeric tonic (whose
non-psoriatic subjects. Psoriasis was resolved by 90% in concentration was not specified) and the other one re-
the curcumin-treated patients after 2–6 weeks (5 out 10 ceiving a placebo tonic. The two formulations – having
subjects) or by 50–85% after 3–8 weeks (the remaining 5 the same color – were applied on the scalp twice daily for
subjects). In the calcipotriol-treated group, 3 patients had 9 weeks. The effectiveness of the treatment was evaluated
70–80% resolution after 4–6 months of treatment and 7 by means of PASI. After completion of the treatment, the
patients had 50–65% improvement after 6–18 months. As mean PASI score in the turmeric-treated group decreased
expected, no improvements of psoriasis occurred in the significantly – from 7 to 3 (−57%) – whereas in the
group of untreated patients. placebo-treated group the PASI score increased from 4 to

Downloaded from [Link] by guest on 30 December 2024

The results of immunochemical measurements 7 (+43%). In the last two studies summarized above [11,
showed that the PhK levels in the groups treated with 12], the anti-psoriatic activity of turmeric was related to
curcumin and calcipotriol decreased by a 5.8- and a 2.2- the capability of curcumin not only to inhibit PhK but
fold compared with the control group, respectively. The also to downregulate receptors of mediators of inflam-
PhK activity in the skin of non-psoriatic subjects was 2- mation, such as 5-lipoxygenase, 5-cyclooxygenase, tumor
fold lower compared with the psoriatic skin treated with necrosis factor-a, interleukin-1, interleukin-6, and
curcumin. Curcumin also reduced keratinocyte trans- interleukin-8.
ferrin receptor expression, severity of parakeratosis, and
density of epidermal CD8+ T cells. Curcumin to Treat Hypertrophic Scarring
A separate OL study was conducted on 6 patients to Hypertrophic scars result from an abnormal inflam-
compare the effect of 1% curcumin alcoholic gel with the matory response of injured skin characterized by an
effect of the vehicle alone. This study confirmed that the overproduction of collagen. They represent an undesir-
observed reduction of the PhK levels in the curcumin- able process in wound healing [49].
treated patients was not influenced by ethanol. The au- Heng et al. [13] have reported six case studies in which a
thors concluded that curcumin is an effective anti- hydro-alcoholic gel of 12% curcumin reduced exceeding
psoriatic agent thanks to its capability of inhibiting PhK. scarring of wounded skin of patients who underwent
The therapeutic value of turmeric in the treatment of excision of a portion of skin affected by carcinoma.
psoriatic lesions was assessed by Serafian et al. [11] in a Curcumin was chosen as a wound-healing agent owing to
randomized, intraindividual, right-left comparative, its capability to inhibit PhK [45] and, consequently, in-
double-blind (DB), placebo-controlled (PC) trial in- terfere with NF-kB activation which is a key step in fi-
volving 40 patients with mild-to-moderate psoriasis. The broblast proliferation and collagen synthesis [50]. Treat-
volunteers applied a hydro-alcoholic gel – containing a ments consisted in topical application of the curcumin gel
turmeric extract or the vehicle alone as the placebo – on twice daily for periods ranging from 2 to 8 weeks.
the right or left lesions twice daily for 9 weeks. The
amount of curcuminoids in the gel was determined ac- Turmeric to Treat Vitiligo
cording to a well-standardized method. However, the Vitiligo is a skin disease characterized by loss of
authors did not detail such a content. The turmeric gel melanocytes and depigmentation. Although the exact
and the placebo gel were identical in their presentation. etiology of vitiligo remains unknown, it is ascertained that
The psoriasis area and severity index (PASI) [48] was it may be related to a chronic autoimmune disorder
assessed to evaluate the clinical efficacy of the treatment. associated with an abnormal inflammatory response [51].
The study was completed by 34 patients. At the end of The well-known anti-inflammatory properties of
the treatment, the turmeric gel was found much more curcumin prompted Jalalmanesh et al. [14] to carry out a
effective than the placebo gel. In fact, the former reduced randomized, DB, PC study in which turmeric was
the mean PASI score from 3.6 to 1.4 (−61%) whereas the evaluated for its effects on skin pigmentation in patients
latter reduced the same score from 3.7 to 3.3 (−11%). The suffering from mild-to-moderate vitiligo. Thirty patients
authors hypothesized that the moisturizing property of were enrolled, and 24 completed the study. Two creams

238 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco
Fig. 1. Structures of curcuminoids: curcu-
min (a), demethoxycurcumin (b), and
bisdemethoxycurcumin (c).

condition are supportive (i.e., massage of the breast to-

ward the nipple to improve breast emptying) and
pharmacological if symptoms do not regress

Downloaded from [Link] by guest on 30 December 2024

(i.e., analgesic, anti-inflammatory, and antibacterial
drugs) [55].
The effectiveness of topical curcumin to treat lacta-
tional mastitis was investigated in a randomized, DB, PC
clinical trial involving 63 breastfeeding women [15]. The
patients were divided into two groups: 32 subjects were
Fig. 2. Keto-enol tautomer of curcumin.
treated with a curcumin cream spray (Neurobiologix, TX,
USA); 31 subjects received a topical moisturizer cream as
the placebo. All patients were asked to apply one pump of
containing turmeric or placebo, identical in appearance, the cream to the affected breast every 8 h. Although the
were given to patients who applied one of the two creams authors did not provide information regarding the
on the right or left side of depigmented skin areas ac- concentration of curcumin in the cream, they specified
cording to a randomized procedure twice daily for 4 the content of curcumin released by each pump (200 mg).
months. The content of turmeric in the cream was not The clinical evaluation was based on a mastitis severity
detailed in the quoted article. Two clinical outcomes were index made up of three different parameters: breast
assessed, namely, the vitiligo area scoring index [52] and tension, erythema, and pain.
the vitiligo noticeability scale (VNS) [53]. After 3 days, the mean values of the symptoms-related
At the end of the treatment, the mean vitiligo area parameters in the curcumin-treated group exhibited
scoring index score of the turmeric-treated skin areas significant favorable changes: tension, erythema, and pain
improved in 14 out of the 24 patients (from 10–25% to decreased from 3.6, 2.5, and 5.2, respectively, to values
more than 50%) whereas treatment with the placebo in 20 below 0.5. In the placebo-treated group, the same pa-
subjects did not lead to any relevant change in this rameters were reduced to a considerably less extent: from
outcome. Regarding the VNS-based assessment, a greater 3.5, 2.9, and 5.6 to 2.4, 2.3, and 3.1, respectively. The
number of patients reported more noticeable patches results of this study show that topical curcumin is a
using the placebo cream while less noticeable patches and valuable anti-inflammatory and antimicrobial agent to
complete responses were recorded in the turmeric manage lactational mastitis.
group. According to the authors, these results support the
topical use of turmeric alone or as adjuvant therapy in Curcumin to Treat Dermatitis Caused by Cancer or
patients suffering from vitiligo. Radiotherapy
The anti-inflammatory and antioxidant properties of
Curcumin to Treat Lactational Mastitis curcumin prompted some authors to test such a sub-
Lactational mastitis is an inflammatory condition stance in relieving symptoms of dermatitis associated
mainly caused by milk stasis in lactiferous ducts which is with cancer or caused by cancer radiotherapy. Curcumin
characterized by a hard, swollen, tense, and erythematous has been employed topically to treat cancerous lesions of
breast accompanied by pain (mastalgia) [54]. Sometimes, skin and mucosae (mouth and vulva) [16]. This non-
mastitis is associated with infection. Treatments for this comparative (NC) clinical trial was conducted on 62

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 239

Studies DOI: 10.1159/000535100
 Wolf et al. [17] on 169 females (those who completed the
study) suffering from breast cancer to compare the ef-
fectiveness of three topical agents in reducing radio-
dermatitis: 4% curcumin gel, a commercially available gel
containing tocopheryl acetate (concentration not given),
and a placebo gel. Most of the skin damage produced by
radiation is principally related to indirect mechanisms
mediated by free radicals; this was the rationale of
Fig. 3. Structure of tetrahydrocurcumin. comparing curcumin versus tocopheryl acetate, both
endowed with strong antioxidant properties. The
blinding of the volunteers was partial because the placebo
patients suffering from recurrent ulcerating tumors gel was the same color (yellow) and consistency as the
characterized by itching, exudates, foul smell, and pain. curcumin gel, whereas the tocopheryl acetate gel was a
All the patients did not respond to standard treatments white lotion. The patients applied the topical agent to
(surgery, chemotherapy, radiotherapy). They were their skin in the radiation area site 3 times daily starting

Downloaded from [Link] by guest on 30 December 2024

treated 3 times daily with 0.5% curcumin in two for- the first day of radiation therapy until 1 week after its
mulations: (i) as an ointment applied on the skin or the completion. Radiation-induced dermatitis was evaluated
vulva and (ii) as a hydro-alcoholic solution (water and according to a radiation-induced dermatitis severity scale.
ethanol 1:1) applied in the oral cavity. During the study, The assessment of the clinical outcomes did not show a
the patients did not receive any anticancer treatment; a significant difference in radiation dermatitis severity
few of them took analgesic drugs, and those hospitalized among the groups of patients treated with the three
received sedative drugs to improve sleep. The skin topical gels.
conditions were evaluated weekly in terms of positive or
negative response of a given symptom to the treatment Curcuma aeruginosa to Treat Androgenic Alopecia
continued not longer than 4 weeks. Androgenetic alopecia is a common form of hair loss
The topical application of curcumin produced bene- in both men and women. In men, this condition is also
ficial effects in most of patients. Particularly, in more than known as male-pattern baldness and has been associ-
90% of the cases the foul smell of the lesions was reduced ated with overactivity of dihydrotestosterone [59].
considerably; in 70% of the patients the exudates de- Therefore, inhibitors of steroid 5-alpha reductase type
creased; the thickness of the lesions was reduced only in 2 – the enzyme converting testosterone in dihy-
10% of the patients. Although half of the patients reported drotestosterone in the epidermis and hair
a decrease in pain, this effect could not clearly be at- follicles – have been claimed as useful agents in the
tributed to curcumin owing to the concomitant admin- treatment of this condition [60]. Curcumin and related
istration of analgesic and sedative drugs. Some patients curcuminoids have been reported to behave as 5-alpha
complained of local irritations likely caused by the eth- reductase type 2 inhibitors [61].
anol content in both topical formulations. Curcumin was A randomized, DB, PC and AC trial evaluated the
not tolerated only in 1 patient due to an allergic reaction. effectiveness of C. aeruginosa [62] (belonging to the same
Despite the limitations in the design of the quoted study, botanical family as C. longa) in the treatment of an-
these results suggest that curcumin may play a beneficial drogenetic alopecia [18]. The study was conducted on 87
role in relieving symptoms related to skin and mucosae men who were divided into four groups to receive twice
cancers. daily for 6 months: (i) 5% n-hexane extract of C. aeru-
A common side effect of cancer radiotherapy is der- ginosa; (ii) 5% minoxidil solution; (iii) C. aeruginosa plus
matitis whose severity is graded in a continuum, ranging minoxidil; and (iv) placebo consisting in a vehicle lacking
from erythema and dry desquamation to the more severe active ingredients. The number of subjects was 21 in the
desquamation and, eventually, ulceration [56, 57]. This first group or 22 in the remaining ones. All volunteers
condition is characterized by symptoms such as skin were instructed to apply three sprays onto the anterior
dryness, itching, discomfort, pain, warmth, and burning and vertex areas twice daily. Additionally, they were
which may lead to the cessation of the treatment or persist required to use the same shampoo and maintain the same
up to a month after its completion [58]. hairstyle, hair length, and hair color during the entire
A randomized, partially blind, PC and active- study and to refrain from cutting the scalp hair shorter
controlled (AC), clinical trial was conducted by Ryan than 1 inch.

240 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco
 A slight increase in hair count was found in the three alopecia. The results of this study did not reveal any
groups treated with active ingredients that, however, did significant improvement of such a formulation on hair
not reach a statistical significance level. The authors state growth. However, it may be relevant to such a finding that
that “C. aeruginosa extract used in the study was con- the amount of curcuminoids present in the n-hexane
trolled for quality by assay for inhibitory activity against extract seems questionable as we have already observed
testosterone conversion by HPLC, as previously de- while summarizing the quoted article.
scribed” but they provide a reference [63] which does not The overall picture emerging from studies #1–7 is that
describe such a procedure. Moreover, the amount of curcumin might represent a valuable therapeutic option
curcuminoids present in the n-hexane extract seems in several skin diseases differing in etiology, but all
questionable as the maximum concentration of these characterized by inflammation, such as psoriasis, hy-
substances in n-hexane does not exceed 0.04% [64]. pertrophic scarring, vitiligo, lactational mastitis, can-
cerous lesions. Some of the above studies are well de-
Remarks about Studies Using Curcumin or Turmeric as signed (#2,3,5,6) and therefore provide a stronger support
a Single Ingredient to such a view. However, further studies remain to be
The clinical studies summarized in this section (#1–9 undertaken to confirm the value of curcumin as a topical

Downloaded from [Link] by guest on 30 December 2024

in Table 1) employed curcumin or turmeric (from here on anti-inflammatory agent.
curcumin) as the only active ingredient of topical for-
mulations. They allow us to appreciate the real thera-
peutic potential of curcumin without confounding con- Curcumin or Turmeric Combined with Other Active
tributions coming from additional pharmacologically Ingredients
active substances present in the same formulation, such as
herb extracts, vitamins, or drugs. In such cases, corre- The articles reviewed in this section refer to the use of
lations between the clinical effects of curcumin and its curcumin or turmeric combined with other active in-
pharmacological properties (antioxidant, anti- gredients mixed in the same formulation to treat various
inflammatory, and antimicrobial) can be attempted. skin conditions.
These studies differ considerably from each other in
their design, namely, case reports (#4), NC trial (#7), OL Turmeric and Sandalwood Oil to Treat Radiodermatitis
trial (#1), and randomized, PC trials (#2,3,5,6,8,9), listed A topical formulation containing a turmeric extract
in increasing order of internal validity. Two of them are and sandalwood oil (Vicco® Turmeric Cream, Vicco
also AC trials (#8,9). Except for two studies (#8,9), the Laboratories, Parel, India) was evaluated by Palatti et al.
remaining ones reached statistically significant results. [19] as a skin-protecting agent in patients undergoing
Studies #1–3 deal with use of curcumin to treat pso- cancer radiotherapy. In this randomized, OL, PC study,
riasis and reinforce each other in terms of robustness of a total of 50 patients with head and neck cancer were
the results. Specifically, the first one (OL) demonstrates equally divided into two groups: the first one treated
that the beneficial effect of curcumin is associated with with 2 g of turmeric cream (concentration not speci-
measurable biochemical and histological changes in the fied) and the second one treated with 2 mL of a
skin of patients; the remaining two are randomized, DB, commercially available moisturizing baby oil as the
PC trials supporting the clinical efficacy of curcumin in placebo. The two formulations were applied on the
terms of statistically significant differences between irradiated skin region 5 times daily for 7 weeks of
curcumin-treated and placebo-treated groups of patients. radiotherapy and 2 weeks after its conclusion. The skin
A key methodological aspect of clinical studies aimed condition of the volunteers was assessed twice weekly
at evaluating curcumin as a topical agent should be es- by a physician who did not mention the details of the
tablishing its exact concentration in the tested formula- trial. The outcome was a severity score made up of 4
tions. Among the nine studies considered in this section, grades of dermatitis [65].
studies #1,4,7–9 detail such data while studies #2,3,5 do The group using the turmeric cream had delayed ap-
not. In study #6, the authors do not specify the con- pearance and reduced levels of dermatitis throughout the
centration of curcumin in the cream applied to treat entire period of the trial (9 weeks). Particularly, grade 3
lactational mastitis but, however, detail the total amount dermatitis was observed at weeks 6 and 7 in 4.3% and 13.6%
of curcumin released per pump (200 mg). The last study of the turmeric cream-treated patients, respectively, com-
examined in this section (#9) evaluated the effect of a 5% pared with 12.5% and 29.2% of incidence, respectively, in
n-hexane extract of C. aeruginosa to treat androgenetic the baby oil-treated patients. None of the patients developed

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 241

Studies DOI: 10.1159/000535100
grade 4 dermatitis in each of the two cohorts. The turmeric clinical efficacy of curcumin combined with piperine and
cream treatment performed better than the baby oil also capsaicin in treating alopecia areata was comparable with
during the 2 weeks after completion of radiotherapy. that offered by minoxidil.
The results of this study using a combination of tur-
meric and sandalwood oil are somehow contrasting with Turmeric and Azadirachta indica to Treat Scabies
those obtained from the study conducted by Ryan Wolf Scabies is an infestation of the skin caused by a tiny mite
et al. [17] on a larger number of patients which found that called Sarcoptes scabiei var. hominis. It represents an en-
4% curcumin was not superior to placebo in treating demic disease in many non-industrialized tropical regions
radiodermatitis (see previous section). This suggests that of the world [72]. Typical symptoms of scabies are intense
the sandalwood oil might exert significant effects in re- itching and skin rash. Scabies is spread by skin-to-skin
lieving radiodermatitis under the experimental condi- contact among persons or by contact with infested clothes.
tions of the study by Palatti et al. [19] (summarized An NC study evaluated the use of turmeric and neem
above). Incidentally, sandalwood album oil has demon- (A. indica) to treat scabies in 824 people living in a village
strated beneficial effects in skin diseases such as acne, located in an Indian district [21]. Neem is endowed with
psoriasis, and eczema, owing to its anti-inflammatory, anti-inflammatory, wound healing, and antimicrobial

Downloaded from [Link] by guest on 30 December 2024

antimicrobial, and antiproliferative activities [66]. activities [73]. Usage of the two plants to treat scabies
However, the two quoted studies cannot be compared in represented a traditional medicine approach offering
terms of design quality as the one by Ruan Wolf et al. was economical and practical advantages over synthetic drugs
DB and PC whereas the one by Palatti et al. [19] was OL. such as benzyl benzoate. Diagnosis of scabies was con-
firmed by a physician. The treatment consisted in the
Curcumin with Piperine and Capsaicin to Treat topical application of a paste containing turmeric powder
Alopecia Areata and fresh neem leaves in the proportion of 1:4 by weight.
Alopecia areata is a transient, non-scarring hair loss Boiling the clothes and a scrub bath were carried out
with preservation of the hair follicle which is seemingly before the treatment. The paste was rubbed all over the
related to autoimmune, genetic, emotional stress, and body of the patient and left to dry. This procedure was
endocrine factors [67]. Mao et al. [20] compared a mixed repeated daily. If the lesions had healed within 15 days of
preparation of 0.1% curcumin, 0.1% piperine, and 0.03% treatment, the patient was considered cured.
capsaicin with a 5% minoxidil tincture for their effec- The results of this study were remarkable as 97.9% of
tiveness in promoting hair growth in patients suffering the 814 patients were cured. Treatment failure occurred
from alopecia areata. The rationale for combining cur- in only 17 cases owing to scarce compliance in the ap-
cumin with piperine and capsaicin was the following: plication of the paste and/or the preliminary procedures
curcumin has anti-inflammatory properties and increases (scrub bath and boiling clothes).
blood circulation [68]; piperine has been reported to
increase the bioavailability of curcumin [69]; capsaicin Turmeric with A. indica and Cassia tora to Treat
improves blood circulation and has shown beneficial Tinea Corporis
effects in alopecia areata [70]. Sixty volunteers (23 males Tinea corporis is a fungal infection affecting the
and 37 females) were enrolled in this randomized, OL, surface layer of the skin caused by dermatophytes, the
AC study. They were randomly assigned to apply on their most widespread types belonging to genera Microspora,
scalp twice daily either the mixed preparation or the Trichophyton, and Epidermophyton. The use of a soap
minoxidil tincture for 12 weeks. The degree of hair loss containing extracts of C. longa, A. indica, and C. tora to
was assessed using the severity of the alopecia tool score treat tinea corporis was investigated in a randomized,
[71] and by dermoscopy. single-blind, PC clinical trial [22]. The medical herbs
After completion of the treatment, statistically sig- employed in this study were selected owing to their
nificant hair growth occurred in both groups as compared proven antifungal activities [74–76]. The contents of the
with the baseline at time 0. The mean severity of the three active ingredients in the antimicrobial soap were
alopecia tool score decreased from 4.4 to 2.2 (−56%) in not specified in the quoted article. Thirty patients affected
the mixed preparation-treated group and from 3.9 to 2.0 by tinea corporis were included in the study. The diag-
(−57%) in the minoxidil-treated group. The count of hair nosis was confirmed by potassium hydroxide (KOH)
follicles by dermoscopy increased by a 3.6-fold and a 3.8- preparation [77]. The volunteers were divided into two
fold in the mixed preparation- and minoxidil-treated groups: 20 in the test group who used the multi-herbal
groups, respectively. According to the authors, the soap and 10 in the placebo group who used a soap similar

242 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco
in color and smell to the tested soap. Participants were The median score of HFS was not significantly dif-
blinded regarding the assigned group. Treatment con- ferent between the two groups at the end of all four
sisted in applying the soap on the affected areas a assessed courses of chemotherapy. However, at the end of
minimum of twice daily and lasted 4 weeks. Two out- each of the first three courses, the rate of HFS grades 1–3
comes were assessed at baseline (time 0) and after occurrence was slower in the curcumin plus henna-
completion of the treatment, namely, total symptom treated group than in the placebo-treated group. The
score and KOH test to reveal the presence or absence of authors concluded that the ointment containing curcu-
fungi. min and henna delays HFS manifestations in patients
On completion of the study, a statistically significant under treatment with oral capecitabine.
reduction in mean total symptom score was observed in
the test group (8.6–3.0), differently from the placebo Turmeric with Herbal Extracts to Treat Eczema
group (8.8–8.1). Moreover, the percentage of patients A commercially available cream (Herbavate®, Troikaa
who turned out negative for KOH preparation was 80% Pharmaceuticals Ltd, Ahmedabad, India) – containing
in the test group and 20% in the placebo group. These extracts of turmeric, Calotropis gigantea, Pongamia gla-
results suggest that the multi-herbal formulation of the bra, Solanum xanthocarpum, Cinnamomum camphora,

Downloaded from [Link] by guest on 30 December 2024

tested soap can be effective against fungal infections of and Juglans regia – was evaluated for its effectiveness in
the skin. the treatment of atopic dermatitis (eczema) [24]. The
concentrations of the herbal extracts in the cream were
Turmeric with Lawsonia inermis to Treat not specified by the authors. This NC study involved 150
Capecitabine-Induced Hand-Foot Syndrome patients. The volunteers were asked to apply the cream
Hand-foot syndrome (HFS) or palmar-plantar er- twice daily for 4 weeks. The primary outcome was a
ythrodysesthesia is a side effect caused by some anti- change in symptoms (erythema, scaling, thickening, and
neoplastic drugs, such as capecitabine (an oral prodrug of itching) assessed after 4 weeks according to a 4-point
5-fluorouracil), characterized by redness, swelling, and score scale as compared to the baseline scores before
pain on the palms of the hands and/or the soles of the feet treatment. The secondary outcome was the weekly
[78]. A randomized, triple-blind, PC study was conducted change in symptom scores as compared to the previous
by Elyasi et al. [23] to evaluate whether a commercially clinical evaluation.
available ointment containing 0.5% turmeric and 10% The trial was completed by 131 patients. After 4 weeks,
henna (L. inermis) could reduce HFS in patients taking the reduction of each of the four symptoms ranged from
oral capecitabine. The rationale of such a topical treat- 28% to 35%. The cream produced statistically significant
ment relied on the anti-inflammatory properties of improvements not only at the end of the trial but also
curcumin and the recognized beneficial effects of henna after each week of treatment. The cream was well tol-
in HFS [79, 80]. erated, with only 4 patients complaining of mild burning
For this study, 110 patients taking capecitabine were at the application site and only 1 patient reporting
enrolled and randomly divided into two groups of 55 hyperpigmentation.
subjects each: one treated with the ointment containing
curcumin and henna (Alpha®, Alpha Development Turmeric with Herbal Extracts to Treat Acne
Company, Tehran, Iran) and the other one treated with A mixture of turmeric with Aloe barbadensis, A. indica,
an ointment as the placebo which was similar in ap- Hemidesmus indicus, Terminalia chebula, Terminalia
pearance to the one with active ingredients. The volun- arjuna, and Withania somnifera was evaluated for its
teers applied twice daily half a fingertip unit of the effectiveness in the treatment of acne vulgaris in a ran-
ointment on the soles and one fingertip unit on the palms. domized, DB, PC trial [25]. No information regarding the
This treatment started from the first day of chemotherapy amounts of the various constituents of topical and oral
with capecitabine and continued consecutively for 4 formulations was given in the quoted article. The poly-
courses of chemotherapy (each course consisted in oral herbal formulation was applied topically as a gel or a
capecitabine on days 1–15 every 3 weeks). Forty-six cream and administered orally as tablets (these latter
patients in the treatment group and 44 patients in the contained Piper longa to improve the bioavailability of
placebo group completed the study. The severity of HFS turmeric). This study lasted 4 weeks and involved 53
was clinically assessed at the end of each of the four patients divided into four groups treated as follows: (i)
chemotherapy courses based on a World Health topical active gel plus active tablets; (ii) topical active
Organization (WHO) scale. cream plus active tablets; (iii) topical placebo plus active

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 243

Studies DOI: 10.1159/000535100
tablets; and (iv) topical placebo plus placebo tablets. All the thorax of patients suffering from MPE [27]. In ad-
patients were asked to take two tablets twice daily and to dition to C. zedoaria, the ointment contained Astragalus
apply the topical formulation twice daily on the affected membranaceus, Semen pharbitidis, cassia twig, Peri-
area. The outcome was a clinical assessment based on a 4- carpium arecae, borneol, and other substances. A total of
point scale ranging from “excellent” to “poor” response. 72 patients were enrolled and equally divided into two
The four treatments showed different performances groups: one using the herbal ointment and the other one
according to the following order of efficacy: (ii) > (i) > using an ointment devoid of active ingredients as the
(iii) > (iv). The superior beneficial effects of the two active placebo. The patients applied the ointment on the thorax
combined therapies compared with the topical placebo wall for 8 h daily. The treatment lasted 2 weeks. The
plus active tablet therapy suggest that the topical treat- outcomes consisted of measurement of the quantity of
ment with herbal extracts gave a significant contribution pleural effusion and clinical evaluations of MPE symp-
to reduction of acne. toms. The study was completed by 33 and 32 patients in
the two groups, respectively.
Turmeric with Herbal Extracts to Treat Pruritus Regarding the pleural effusion volume, no statisti-
A commercially available cream (“itch cream”) con- cally significant differences were observed between the

Downloaded from [Link] by guest on 30 December 2024

taining turmeric together with several additional active treatment group and the placebo group. However, the
ingredients was evaluated for its effectiveness as symp- clinical evaluation of symptoms of MPE showed that
tomatic relief of pruritus in various dermatological dis- the treatment with herbal extracts was superior to the
orders like atopic dermatitis, senile pruritus, and ichthyosis treatment with the placebo. The authors did not pro-
[26]. The composition of the cream was the following: vide pharmacological basis as a rationale to support
16.0% turmeric, 8.0% Santalum album, 3.0% L. inermis, their study.
3.0% Ocimum sanctum, 0.5% Glycyrrhiza glabra, 0.5%
Vetiveria zizanioides, 0.5% surasar, 0.1% Abelmoschus Curcumin with Active Ingredients to Treat Skin Aging
moschatus, 0.1% turmeric oil, 0.025% Crocus sativus, Di Lorenzo et al. [28] evaluated a cream composed of
0.00032% Swarna Bhasma. This randomized, OL, AC trial 0.02% curcumin, 1.0% tocopheryl acetate, 1.0% Acerola
involved 64 subjects who were divided into two groups: fruit extract, and 0.5% selenomethionine calcium phos-
those treated with the itch cream and those treated with a phate for its capability of reducing facial skin aging in 60
commercially available cream (Moisturex® Cream, Cros- women aging between 45 and 60. The volunteers were
lands) as active control containing the following constit- divided into three groups each of 20 subjects: (i) a cream-
uents: 10% urea, 10% lactic acid, 10% propylene glycol, 10% treated group (cosmeceutical formulation); (ii) a group
light liquid paraffin. The patients were instructed to apply treated with the cream and a dietary supplement (nu-
the cream (tested or control) topically twice daily as a thin tricosmetic formulation) corresponding to a turmeric
film over the affected area without rubbing or massaging. extract containing 70 mg of curcuminoids taken once
No topical or systemic antihistaminic or corticosteroid daily; and (iii) a placebo group made up by subjects
drugs were allowed to use during the trial. The outcome treated with a cream lacking active ingredients. The
was a clinical assessment of pruritus according to a 3-point following skin parameters were assessed through in-
score scale. The baseline scores were recorded after en- strumental measurements at the beginning of the treat-
rollment, and the volunteers were instructed to attend three ment, after 2 weeks, and after completion of the trial (4
weekly follow-up visits. The study was completed by 25 weeks): water loss, hydration, elasticity/firmness, dermal
subjects in group A and 21 subjects in group B. The results thickness, and wrinkles.
showed that the cream containing polyherbal extracts was Both the cosmeceutical and nutricosmetic formulations
not superior to placebo in reducing pruritus. were found effective in improving skin quality compared
with the placebo. The nutricosmetic product performed
Curcuma zedoaria with Herbal Extracts to Treat generally better than the cosmeceutic one, except for the
Malignant Pleural Effusion hydration test where they gave equivalent results.
Malignant pleural effusion (MPE) is a metastatic in-
volvement of the pleura from primary malignancy at Remarks about Studies Using Curcumin or Turmeric
lung, breast, and other body sites [81]. Feize et al. [82] Combined with Other Active Ingredients
described the results of a randomized, DB, PC study The ten clinical studies summarized in this section
aimed at investigating the effects of an ointment con- (#10–19 in Table 1) deal with curcumin or turmeric (from
taining Curcuma zedoaria and other active ingredients on here on curcumin) combined with pharmacologically

244 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco
active substances – especially herbal extracts – mixed in treated with combination therapy (group A) and the
the same topical formulation to treat various skin con- other with a targeted narrowband UVB alone (group B).
ditions. For all of them, the use of curcumin was justified The UVB treatments were carried out twice weekly for 12
by its recognized reputation of anti-inflammatory, anti- weeks. The degree of repigmentation, documented by
oxidant, and antimicrobial agent. monthly digital photography, was assessed by a blinded
The considered clinical trials differ in the quality of dermatologist using a 9-point score scale.
design (e.g., NC, OL comparative, DB comparative). An The repigmentation acquired at the end of the study
important caveat of these studies is that they do not allow improved in groups A and B with increased scores of 1.9
to single out the potential beneficial effect of curcumin. In and 1.7 compared with the baseline score of 0, respec-
other words, any trial making use of a mixture of active tively. The authors affirmed that the combination
ingredients, all employed at fixed concentrations, pro- treatment of tetrahydrocurcuminoids plus UVB therapy
vides information on the clinical efficacy of that specific was more effective than UVB monotherapy in reducing
mixture without enabling any inference regarding the vitiligo although, due to the relatively small sample size,
efficacy of each single ingredient. This implies that the the results did not reach statistically significant levels.
combination of curcumin with active substances in these

Downloaded from [Link] by guest on 30 December 2024

studies, regardless to their design, represents the un- Tetrahydrocurcumin with Herbal Extracts to Treat
avoidable bottleneck of the information concerning the Photoaging
potential beneficial effects of curcumin. Therefore, it is A gel containing tetrahydrocurcumin and other active
impossible to reach sound conclusions about the utility of ingredients (Tricutan®, Adderma AB, Stockholm, Sweden)
curcumin as a single ingredient by looking at the sta- was tested in 28 women to evaluate its effectiveness in
tistically significance of the results. However, the studies improving skin firmness and elasticity in photoaged facial
presented in this section, especially those in which cur- skin [84]. This randomized, DB, PC trial lasted 4 weeks and
cumin was combined with no more than three active was based on self-assessment, clinical examination, and a
ingredients, may prompt researchers to undertake novel quantitative endpoint of cutaneous elasticity and firmness.
clinical trials using curcumin alone to gain a deeper This latter was carried out by using a Reviscometer mea-
insight on the real therapeutic value of this substance. suring shear wave propagation in the skin [85]. The active
components of the gel were 0.1% tetrahydrocurcumin, 0.3%
Rosmarinus officinalis water extract, 0.3% dimethylami-
Tetrahydrocurcumin as an Alternative to Curcumin noethanol, 0.1% Centella asiatica butylene glycol extract.
The placebo was a gel identical in color, smell, and con-
Tetrahydrocurcumin (5) (Fig. 3) is one of the chem- sistency to the Tricutan gel. Each woman applied both gel
ically related compounds of curcumin present in turmeric formulations (active or placebo) on the left or right part of
in small amounts and is also a metabolite of curcumin. It her face according to a random coded list. The gel was
is derived by the reduction of the two olefinic bonds of applied twice daily for 4 weeks. Three women out of the 28
curcumin. Tetrahydrocurcuminoids include tetrahy- included did not complete the study. The reason for dis-
drocurcumin and its derivatives. These are colorless continuing was mild irritative contact dermatitis. Three
substances differing from each other in the substituents further women did not fill out the self-assessment form.
attached to the phenyl rings. The instrumental measurements showed a statistically
significant improvement in skin firmness in the Tricutan-
Tetrahydrocurcuminoids Combined with UVB treated half-face with respect to the placebo-treated half-
Radiations to Treat Vitiligo face. The clinical evaluations and the self-assessments
Tetrahydrocurcuminoids were evaluated in an OL, also showed Tricutan to give more beneficial effects on
comparative study for their capability to induce skin quality compared with the placebo.
repigmentation in 10 patients suffering from vitiligo in
combination with narrowband UVB phototherapy [83]. Remarks about Studies on Tetrahydrocurcumin
These substances were the constituents of a commercially Tetrahydrocurcumin offers a considerable advantage
available curcuminoid cream (GPO Curmin, Govern- over curcumin as consumers do not like products that dye
ment Pharmaceutical Organization, Bangkok, Thailand). their skin. However, the results of clinical trials per-
Their content in the cream was not given. For each formed using tetrahydrocurcumin should be considered
subject, two target lesions within the same anatomical bearing in mind that this substance, as outlined by
area were chosen. One patch was randomly assigned to be Aggarwal et al. [86], does not exhibit the same

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 245

Studies DOI: 10.1159/000535100
pharmacological profile of curcumin. The quoted review skin diseases, such as vitiligo, or to improve skin firmness
provides examples of biological activities in which cur- although these substances display non-identical phar-
cumin was found more active than tetrahydrocurcumin macological properties. Further research is probably
together with others in which, on the opposite, tetra- needed to compare the effectiveness of curcumin and
hydrocurcumin performed better than curcumin. tetrahydrocurcumin in dermatology.
To sum up, in most of the clinical studies discussed in
this review curcumin has been regarded as an attractive
Conclusions alternative to conventional drugs, such as corticosteroids
and antibiotics, thanks to its characteristics of a safe and
To date, the number of articles reporting on the well-tolerated natural substance. Literature offers some
evaluation of topical curcumin or turmeric (from here on examples of how curcumin can be useful as a topical agent
curcumin) in humans is relatively low compared with the in skin diseases and health care, thus paving a way to new
vast literature describing their pharmacological proper- clinical studies aimed to explore its full therapeutic
ties at the molecular level, in cells, tissues, and animal potential.
models as well as the effects of their oral administration

Downloaded from [Link] by guest on 30 December 2024

[87]. In the present article, we have reviewed 19 clinical
studies in which curcumin was tested alone or combined Acknowledgment
with additional active ingredients in the same topical
formulation to treat various skin conditions. The studies The assistance of the Athenaeum library staff is gratefully
appreciated.
based on the use of curcumin alone offer a clear advantage
in terms of information concerning the real therapeutic
efficacy of curcumin as an anti-inflammatory, antioxi-
Conflict of Interest Statement
dant, and antimicrobial topical agent.
Curcumin is practically insoluble and highly unstable The authors have no conflicts of interest to declare.
in aqueous solutions with neutral-to-alkaline pH values
where hydrolysis, oxidation, and photodegradation re-
actions take place [40, 41]. Such unfavorable chemical Funding Sources
properties hamper the topical use of curcumin, although
higher solubility and stability can be achieved by dis- This research received no external funding.
solving it in alcoholic solutions, oil-in-water emulsions,
and ointments. Therefore, technological approaches to
optimize the topical delivery of curcumin have been Author Contributions
devised [5, 6]. The works of Lademann’ group occupy a
Conceptualization and writing original draft preparation,
prominent position in this field of research [88–90]. Giovanni Greco; methodology, Giovanni Greco and Sonia
The intense yellow color of curcumin is undoubtedly Laneri; software, Federica Forgione; investigation, Giovanni
an organoleptic undesirable factor for a daily topical Greco and Ritamaria Di Lorenzo; resources, Giovanni Greco
usage [1]. This also represents a key issue in PC trials that and Antonia Sacchi; data curation, Giovanni Greco, Ritamaria
should be properly managed by researchers and ad- Di Lorenzo, Federica Forgione, and Antonietta Bernardi;
dressed in their articles (i.e., by detailing the color and the writing review and editing, Giovanni Greco, Sonia Laneri, and
Ritamaria Di Lorenzo; visualization, Ritamaria Di Lorenzo,
composition of the placebo). In this regard, tetrahy- Federica Forgione, and Giovanni Greco; supervision, Sonia
drocurcumin, a colorless derivative of curcumin, has been Laneri. All authors have read and agreed to the published
employed to surrogate curcumin in the treatment of some version of the manuscript.

References

1 Arct J, Ratz-Łyko A, Mieloch M, Witulska M. chemistry, safety, pharmacological activities, sessment of a highly bioavailable curcumin-
Evaluation of skin colouring properties of and clinical applications of turmeric: a galactomannoside complex (CurQfen) in
curcuma longa extract. Indian J Pharm Sci. mechanistic review. Evid Based Complement healthy volunteers, with a special reference to
2014;76(4):374–8. Alternat Med. 2020;2020:7656919–4. the recent hepatotoxic reports of curcumin
2 Ahmad RS, Hussain MB, Sultan MT, Arshad 3 Pancholi V, Smina TP, Kunnumakkara AB, supplements: a 90-days prospective study.
MS, Waheed M, Shariati MA, et al. Bio- Maliakel B, Krishnakumar IM. Safety as- Toxicol Rep. 2021;8:1255–64.

246 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco
 4 Anand P, Kunnumakkara A, Newman R, inhibitor in the treatment of male-pattern 32 Value calculated by XLogP3 ver. 3.0 program,
Aggarwal B. Bioavailability of curcumin: baldness: a multicenter, randomized, PubChem release 2021.
problems and promises. Mol Pharm. 2007; double-blind, placebo-controlled study. 33 Cheng T, Zhao Y, Li X, Lin F, Xu Y, Zhang X,
4(6):807–18. J Dermatolog Treat. 2012;23(5):385–92. et al. Computation of octanol-water partition
5 Naksuriya O, Okonogi S, Schiffelers RM, 19 Palatty PL, Azmidah A, Rao S, Jayachander coefficients by guiding an additive model
Hennink WE. Curcumin nanoformulations: a D, Thilakchand KR, Rai MP, et al. Topical with knowledge. J Chem Inf Model. 2007;
review of pharmaceutical properties and pre- application of a sandal wood oil and turmeric 47(6):2140–8.
clinical studies and clinical data related to cancer based cream prevents radiodermatitis in head 34 O’Neil MJ, editor 5th ed. The Merck
treatment. Biomaterials. 2014;35(10):3365–83. and neck cancer patients undergoing external Index – an encyclopedia of chemicals, drugs
6 Waghule T, Gorantla S, Rapalli VK, Shah P, beam radiotherapy: a pilot study. Br J Radiol. and biologicals. Cambridge, UK: Royal So-
Dubey SK, Saha RN, et al. Emerging trends in 2014;87(1038):20130490. ciety of Chemistry; 2013. p. 474.
topical delivery of curcumin through lipid 20 Mao Y, Xu Z, Song J, Xie Y, Mei X, Shi W. 35 Kurien BT, Singh A, Matsumoto H, Scofield
nanocarriers: effectiveness in skin disorders. Efficacy of a mixed preparation containing RH. Improving the solubility and pharma-
AAPS PharmSciTech. 2020;21(7):284–95. piperine, capsaicin and curcumin in the cological efficacy of curcumin by heat treat-
7 Canistro D, Chiavaroli A, Cicia D, Cimino F, treatment of alopecia areata. J Cosmet Der- ment. Assay Drug Dev Technol. 2007;5(4):
Currò D, Dell’Agli M, et al. The pharmaco- matol. 2022;21(10):4510–4. 567–76.
logical basis of the curcumin nutraceutical 21 Charles V, Charles SX. The use and efficacy of 36 Jagannathan R, Abraham PM, Poddar P.
use. Pharmadvances. 2021;2:421–66. Azadirachta indica ADR (“Neem”) and Cur- Temperature-dependent spectroscopic evi-
8 Aggarwal BB, Sung B. Pharmacological basis cuma longa (“Turmeric”) in scabies. A pilot dences of curcumin in aqueous medium: a

Downloaded from [Link] by guest on 30 December 2024

for the role of curcumin in chronic diseases: study. Trop Geogr Med. 1992;44(1–2):178–81. mechanistic study of its solubility and sta-
an age-old spice with modern targets. Trends 22 RTK, Bhat MDA, Zaman R, Najar FA. Effi- bility. J Phys Chem B. 2012;116(50):
Pharmacol Sci. 2009;30(2):85–94. cacy of herbal anti-microbial soap in Tinea 14533–40.
9 Vaughn AR, Branum A, Sivamani RK. Effects corporis: a randomized controlled study. 37 Manoleva Y, Deneva V, Antonov L, Dra-
of turmeric (Curcuma longa) on skin health: a J Ethnopharmacol. 2022;287:114934. kalska E, Momekova D, Lambov N. The effect
systematic review of the clinical evidence. 23 Elyasi S, Rasta S, Taghizadeh-Kermani A, of the water on the curcumin tautomerism.
Phytother Res. 2016;30(8):1243–64. Hosseini S. Topical henna and curcumin Spectrochim Acta A Mol Biol Spectrosc.
10 Heng MC, Song MK, Harker J, Heng MK. (Alpha®) ointment efficacy for prevention of 2014;11:132–815.
Drug-induced suppression of phosphorylase capecitabine induced hand-foot syndrome: a 38 Tønnesen HH, Karlsen J. Studies on cur-
kinase activity correlates with resolution of randomized, triple-blinded, placebo- cumin and curcuminoids. VI. Kinetics of
psoriasis as assessed by clinical, histological controlled clinical. Daru. 2022;30(1):117–25. curcumin degradation in aqueous solution.
and immunohistochemical parameters. Br 24 Rawal RC, Shah BJ, Jayaraaman AM, Jaiswal Z Lebensm Unters Forsch. 1985;180(5):
J Dermatol. 2000;143(5):937–49. V. Clinical evaluation of an indian polyherbal 402–4.
11 Sarafian G, Afshar M, Mansouri P, Asgar- topical formulation in the management of 39 Horosanskaia E, Yuan L, Seidel-Morgenstern
panah J, Raoufinejad K, Rajabi M. Topical eczema. J Altern Complement Med. 2009; A, Lorenz H. Purification of curcumin from
turmeric microemulgel in the management of 15(6):669–72. ternary extract-similar mixtures of curcu-
plaque psoriasis; a clinical evaluation. Iran 25 Lalla JK, Nandedkar SY, Paranjape MH, minoids in a single crystallization step.
J Pharm Res. 2015;14(3):865–76. Talreja NB. Clinical trials of ayurvedic for- Crystals. 2020;10(3):206–20.
12 Bahraini P, Rajabi M, Mansouri P, Sarafian G, mulations in the treatment of acne vulgaris. 40 Mondal S, Ghosh S, Moulik SP. Stability of
Chalangari R, Azizian Z. Turmeric tonic as a J Ethnopharmacol. 2001;78(1):99–102. curcumin in different solvent and solution
treatment in scalp psoriasis: a randomized 26 Chatterjee S, Datta RN, Bhattacharyya D, media: UV-visible and steady-state fluores-
placebo-control clinical trial. J Cosmet Der- Bandopadhyay SK. Emollient and antipru- cence spectral study. J Photochem Photobiol,
matol. 2018;17(3):461–6. ritic effect of itch cream in dermatological B. 2016;158:212–8.
13 Heng MC. Wound healing in adult skin: disorders: a randomized controlled trial. In- 41 Kharat M, Du Z, Zhang G, McClements DJ.
aiming for perfect regeneration. Int dian J Pharmacol. 2005;37(4):253–4. Physical and chemical stability of curcumin
J Dermatol. 2011;50(9):1058–66. 27 Feize W, Meng L, Yanni L, Yuan L, Liqun J, in aqueous solutions and emulsions: impact
14 Jalalmanesh S, Mansouri P, Rajabi M, Monji Tong L, et al. A randomized controlled study of pH, temperature, and molecular envi-
F. Therapeutic effects of turmeric topical to observe the efficacy of external treatment ronment. J Agric Food Chem. 2017;65(8):
cream in vitiligo: a randomized, double-blind, with a traditional Chinese medicine herbal 1525–32.
placebo-controlled pilot study. J Cosmet ointment on malignant plural effusion: out- 42 Mondal S, Ghosh S, Moulik SP. Colloidal
Dermatol. 2022;21(10):4454–61. come report and design review. Integr Cancer dispersions of lipids and curcumin, and the
15 Afshariani R, Farhadi P, Ghaffarpasand F, Ther. 2017;16(4):473–8. solubility and degradation kinetics of the
Roozbeh J. Effectiveness of topical curcumin for 28 Di Lorenzo R, Grumetto L, Sacchi A, Laneri S, latter in micellar solution. Soft Mater. 2015;
treatment of mastitis in breastfeeding women: a Dini I. Dermocosmetic evaluation of a nu- 13(2):118–25.
randomized, double-blind, placebo-controlled tricosmetic formulation based on Curcuma. 43 Gordon ON, Luis PB, Sintim HO, Schneider
clinical trial. Oman Med J. 2014;29:330–4. Phytother Res. 2023;37(5):1900–10. C. Unraveling curcumin degradation: au-
16 Kuttan R, Sudheeran PC, Josph CD. Tur- 29 Jiang T, Ghosh R, Charcosset C. Extraction, toxidation proceeds through spiroepoxide
meric and curcumin as topical agents in purification and applications of curcumin and vinylether intermediates en route to the
cancer therapy. Tumori. 1987;73(1):29–31. from plant materials: a comprehensive re- main bicyclopentadione. J Biol Chem. 2015;
17 Ryan Wolf J, Gewandter JS, Bautista J, view. Trends Food Sci Technnol. 2021;112: 290(8):4817–28.
Heckler CE, Strasser J, Dyk P, et al. Utility of 419–30. 44 Vanscott EJ, Ekel TM. Kinetics of hyperplasia
topical agents for radiation dermatitis and 30 Nelson KM, Dahlin JL, Bisson J, Graham J, in psoriasis. Arch Dermatol. 1963;88(4):
pain: a randomized clinical trial. Support Pauli GF, Walters MA. The essential me- 373–81.
Care Cancer. 2020;28(7):3303–11. dicinal chemistry of curcumin. J Med Chem. 45 Heng MC, Song MK, Heng MK. Elevated
18 Pumthong G, Asawanonda P, Varothai S, 2017;60(5):1620–37. phosphorylase kinase activity in psoriatic
Jariyasethavong V, Triwongwaranat D, Su- 31 Pabon HJ. A synthesis of curcumin and re- epidermis: correlation with increased phos-
thipinittharm P, et al. Curcuma aeruginosa, a lated compounds. Recl Trav Chim Pays Bas. phorylation and psoriatic activity. Br
novel botanically derived 5α-reductase 1964;83(4):379–86. J Dermatol. 1994;130(3):298–306.

Curcumin as a Topical Agent in Clinical Skin Pharmacol Physiol 2023;36:235–248 247

Studies DOI: 10.1159/000535100
46 Brushia RJ, Walsh DA. Phosphorylase kinase: 62 Burapan S, Kim M, Paisooksantivatana Y, 77 Ely JW, Rosenfeld S, Seabury Stone M. Di-
the complexity of its regulation is reflected in Eser BE, Han J. Thai Curcuma species: an- agnosis and management of tinea infections.
the complexity of its structure. Front Biosci. tioxidant and bioactive compounds. Foods. Am Fam Physician. 2014;90(10):702–10.
1999;4:618–41. 2020;9:1219–29. 78 Ramasubbu MK, Maji S, Padhan M, Maiti R,
47 Reddy S, Aggarwal BB. Curcumin is a non- 63 Zarghi A, Jenabi M, Ebrahimian AJ. HPLC Hota D, Majumdar SKD, et al. Chemotherapy-
competitive and selective inhibitor of phos- determination of the stability of tretinoin in induced hand foot syndrome: comparative
phorylase kinase. FEBS Lett. 1994;341(1):19–22. tretinoin–minoxidil solution. Pharm Acta efficacy and safety of pharmacological pro-
48 Fredriksson T, Pettersson U. Severe psoria- Helv. 1998;73(3):163–5. phylaxis: systematic review and bayesian
sis--oral therapy with a new retinoid. Der- 64 Rachmaniah O, Muhsin MR, Widya AP, network meta-analysis. BMJ Support Palliat
matologica. 1978;157(4):238–44. Rachimoellah M. Process development for Care. 2022. spcare-2022-004011
49 Mony MP, Harmon KA, Hess R, Dorafshar the enrichment of curcuminoids in the ex- 79 Ilyas S, Wasif K, Saif MW. Topical henna
AH, Shafikhani SH. An updated review of tract of ionic type of NADES. IOP Conf Ser: ameliorated capecitabine-induced hand–foot
hypertrophic scarring. Cells. 2023;12(5):678. Mater Sci Eng. 2020;732(1):012005. syndrome. Cutan Ocul Toxicol. 2014;33(3):
50 Chen A, Zheng S. Curcumin inhibits con- 65 Cox JD, Stetz J, Pajak TF. Toxicity criteria of 253–5.
nective tissue growth factor gene expression the Radiation Therapy Oncology Group 80 Yucel I, Guzin G. Topical henna for capeci-
in activated hepatic stellate cells in vitro by (RTOG) and the European Organization for tabine induced hand-foot syndrome. Invest
blocking NF-kappaB and ERK signalling. Br Research and Treatment of Cancer (EORTC). New Drugs. 2008;26(2):189–92.
J Pharmacol. 2008;153(3):557–67. Int J Radiat Oncol Biol Phys. 1995;31(5): 81 Dixit R, Agarwal KC, Gokhroo A, Patil CB,
51 Manga P, Elbuluk N, Orlow SJ. Recent ad- 1341–6. Meena M, Shah NS, et al. Diagnosis and

Downloaded from [Link] by guest on 30 December 2024

vances in understanding vitiligo. F1000Res. 66 Moy RL, Levenson C. Sandalwood album oil management options in malignant pleural
2016;5:2234–9. as a botanical therapeutic in dermatology. effusions. Lung India. 2017;34(2):160–6.
52 Kawakami T, Hashimoto T. Disease severity J Clin Aesthet Dermatol. 2017;10:34–9. 82 Lobo R, Prabhu KS, Shirwaikar A, Shirwaikar
indexes and treatment evaluation criteria in 67 Pratt CH, King LE Jr, Messenger AG, A. Curcuma zedoaria Rosc. (white turmeric):
vitiligo. Dermatol Res Pract. 2011;2011:750342. Christiano AM, Sundberg JP. Alopecia areata. a review of its chemical, pharmacological and
53 Batchelor JM, Tan W, Tour S, Yong A, Nat Rev Dis Primers. 2017;3:17011. ethnomedicinal properties. J Pharm Phar-
Montgomery AA, Thomas KS. Validation of the 68 Barbalho SM, de Sousa Gonzaga HF, de macol. 2009;61(1):13–21.
vitiligo noticeability scale: a patient-reported Souza GA, de Alvares Goulart R, de Sousa 83 Asawanonda P, Klahan SO. Tetrahy-
outcome measure of vitiligo treatment suc- Gonzaga ML, de Alvarez Rezende B. Der- drocurcuminoid cream plus targeted nar-
cess. Br J Dermatol. 2016;174(2):386–94. matological effects of Curcuma species: a rowband UVB phototherapy for vitiligo: a
54 Pevzner M, Dahan A. Mastitis while breast- systematic review. Clin Exp Dermatol. 2021; preliminary randomized controlled study.
feeding: prevention, the importance of proper 46(5):825–33. Photomed Laser Surg. 2010;28(5):679–84.
treatment, and potential complications. J Clin 69 Shoba G, Joy D, Joseph T, Majeed M, Ra- 84 Sommerfeld B. Randomised, placebo-
Med. 2020;9(8):2328–33. jendran R, Srinivas PS. Influence of piperine controlled, double-blind, split-face study on
55 Jajanfar S, Ng CL, Teng CL. Antibiotics for on the pharmacokinetics of curcumin in the clinical efficacy of Tricutan on skin
mastitis in breastfeeding women. Cochrane animals and human volunteers. Planta Med. firmness. Phytomedicine. 2007;14(11):711–5.
Database Syst Rev. 2009;1:CD005458. 1998;64(4):353–6. 85 Xin S, Man W, Fluhr JW, Song S, Elias PM,
56 Bolderston A, Lloyd NS, Wong RK, Holden L, 70 Ehsani AH, Toosi S, Seirafi H, Akhyani M, Man MQ. Cutaneous resonance running time
Robb-Blenderman L. Supportive care guidelines Hosseini M, Azadi R, et al. Capsaicin vs. varies with age, body site and gender in a
group of cancer care Ontario program in clobetasol for the treatment of localized al- normal Chinese population. Skin Res Tech-
evidence-based care - the prevention and man- opecia areata. J Eur Acad Dermatol Venereol. nol. 2010;16(4):413–21.
agement of acute skin reactions related to radi- 2009;23(12):1451–3. 86 Aggarwal BB, Deb L, Prasad S. Curcumin
ation therapy: a systematic review and practice 71 Olsen EA, Hordinsky MK, Price VH, Roberts differs from tetrahydrocurcumin for molec-
guideline. Support Care Cent. 2006;14:802–7. JL, Shapiro J, Canfield D, et al. Alopecia ular targets, signaling pathways and cellular
57 Salvo N, Barnes E, van Draanen J, Stacey E, areata investigational assessment guidelines: responses. Molecules. 2014;20(1):185–205.
Mitera G, Breen D, et al. Prophylaxis and part II. J Am Acad Dermatol. 2004;51(3): 87 Yeung AW, Horbańczuk M, Tzvetkov NT,
management of acute radiation-induced skin 440–7. Mocan A, Carradori S, Maggi F, et al. Cur-
reactions: a systematic review of the litera- 72 Arlian LG, Morgan MS. A review of Sarcoptes cumin: total-scale analysis of the scientific
ture. Curr Oncol. 2010;17(4):94–112. scabiei: past, present and future. Parasit literature. Molecules. 2019;24(7):1393–406.
58 Naylor W, Mallett J. Management of acute Vectors. 2017;10(1):297–308. 88 Suwannateep N, Wanichwecharungruang S,
radiotherapy induced skin reactions: a literature 73 Alzohairy MA. Therapeutics role of Azadir- Haag SF, Devahastin S, Groth N, Fluhr JW, et al.
review. Eur J Oncol Nurs. 2001;5(4):221–33. achta indica (Neem) and their active con- Encapsulated curcumin results in prolonged
59 Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro stituents in diseases prevention and treat- curcumin activity in vitro and radical scavenging
G, Lenzi A, et al. Androgenetic alopecia: a ment. Evid Based Complement Alternat Med. activity ex vivo on skin after UVB-irradiation.
review. Endocrine. 2017;57(1):9–17. 2016;2016:7382506. Eur J Pharm Biopharm. 2012;82(3):485–90.
60 Dhurat R, Sharma A, Rudnicka L, Kroum- 74 Luthra PM, Singh R, Chandra R. Therapeutic 89 Suwannateep N, Wanichwecharungruang S,
pouzos G, Kassir M, Galadari H, et al. 5- uses of Curcuma longa (turmeric). Indian Fluhr J, Patzelt A, Lademann J, Meinke MC.
Alpha reductase inhibitors in androgenetic J Clin Biochem. 2001;16(2):153–60. Comparison of two encapsulated curcumin
alopecia: shifting paradigms, current con- 75 Biswas K, Chattopadhyay I, Banerjee RK, particular systems contained in different
cepts, comparative efficacy, and safety. Der- Bandyopadhyay U. Biological activities and formulations with regard to in vitro skin
matol Ther. 2020;33(3):13379–83. medicinal properties of neem (Azadirachta penetration. Skin Res Technol. 2013;19:1–9.
61 Srivilai J, Rabgay K, Khorana N, Waranuch indica). Curr Sci. 2002;82:1336–45. 90 Jacobi U, Tassopoulos T, Surber C, Lade-
N, Nuengchamnong N, Wisuitiprot W, et al. 76 Ashok PH, Priscilla MD. Antifungal activity mann J. Cutaneous distribution and locali-
Anti-androgenic curcumin analogues as of methanolic extract of Cassia tora leaves zation of dyes affected by vehicles all with
steroid 5-alpha reductase inhibitors. Med against Candida albicans. Int J Res Ayurveda different lipophilicity. Arch Dermatol Res.
Chem Res. 2017;26(7):1550–6. Pharm. 2011;2:793–6. 2006;297(7):303–10.

248 Skin Pharmacol Physiol 2023;36:235–248 Di Lorenzo/Forgione/Bernardi/Sacchi/

DOI: 10.1159/000535100 Laneri/Greco