Ferulic acid –A novel topical agent in reducing signs of
| Renata Dębowska
| Anna Kołodziejczak
Department of Cosmetology and Aesthetic
Dermatology, Faculty of Pharmacy, Medical
University of Ł
Centre for Science and Research Dr Irena
Eris, Warsaw, Poland
nska-Pęciak, Department of
Cosmetology and Aesthetic Dermatology,
Faculty of Pharmacy, Medical University of
nskiego 1 Street, PL-91-151 Ł
Medical University of Ł
Continuous production of reactive oxygen species, induced by UV radiation, is one of
the main mechanisms contributing to skin photoaging. Therefore, the use of novel
superior antioxidants, which ferulic acid belongs to, is an innovative treatment
option. The aim of this study was to evaluate the effect of 14% ferulic acid peel on
skin hydration, topography, the level of melanin, and the severity of erythema, in
people with skin photoaging symptoms. Twenty women aged 45–60, received eight
treatments of chemical peeling in 1-week intervals. Efficacy was measured using The
Multi Probe Adapter (MPA) Systems (Courage +Khazaka electronic GmbH, Köln,
Germany). The measurements were taken before, 8, and 12 weeks after the first
treatment. Additionally, the photo documentation was made with Fotomedicus (Elfo)
Complexion Analysis System (Canfield Scientific, Inc.). The objective eval-
uation showed statistically significant improvement in all measured skin parameters
p< 0.05). The best results of skin hydration and melanin level were observed right
after the end of the series (p< 0.001). The best improvement in erythema reduction
was noted a month after the last treatment (p< 0.0001). At the control, untreated
point none of the probes showed statistically significant changes. In conclusion, a
series of treatments with 14% ferulic acid peel has a significant bleaching, erythema-
reducing, and moisturizing activity. The results achieved by apparatus, are reflected
by photo documentation. The effects achieved during a series persist over time.
antioxidant, chemical peel, ferulic acid, photoaging
Exposure to ultraviolet radiation may contribute to the increase in
reactive oxygen species (ROS), which may be connected with all sorts
of negative biochemical processes within the skin. The free oxygen
radicals are considered to be one of the major causes of elastosis
(accumulation of tropoelastin aggregates in photoaging skin).
other signs of photoaging such as wrinkles, dryness, hyper-
pigmentation, telangiectasia, are also closely related to oxidative
On this basis, it is suggested that the strong antioxidant
compounds, given either orally or applied topically on the skin, could
reduce and prevent the signs of photoaging.
Ferulic acid ([E]-3-[4-hydroxy-3-methoxy-phenyl] prop-2-enoic
acid) (Figure 1) is a phenolic antioxidant found in high concentration
in plant tissues.
In plants, it is biosynthesized from the action of O-
methyl transferase on caffeic acid.
It has low toxicity and many
proven physiological functions (antioxidant,
). The most important prop-
erty of it is its function as an antioxidant. It has been shown to be use-
ful in counteracting skin photoaging because it has the ability to
Received: 21 January 2022 Accepted: 24 April 2022
Dermatologic Therapy. 2022;e15543. wileyonlinelibrary.com/journal/dth © 2022 Wiley Periodicals LLC. 1of8
function as an antioxidant in sunburn cells. Ferulic acid is able to
absorb UVA (cis-ferulic acid—peak at 317 nm; trans-ferulic acid—
236 and 322 nm).
Until recently, this compound was used synergis-
tically together with other antioxidants such as vitamin C and E,
increasing their effectiveness and participating in their regeneration
After oral administration, the bioavailability of ferulic acid
in the skin is relatively low.
Formulas enriched with ferulic acid gain several times higher anti-
oxidant and photoprotective efficacy than those without it. The effec-
tiveness of ferulic acid, as a strong antioxidant reducing UV-induced
oxidative skin damage, as well as inhibiting the formation of hyper-
pigmentation and accelerating skin regeneration, has been proved in
numerous studies on cell cultures of fibroblasts, keratinocytes, and
The results of these studies are promising positive
and would qualify ferulic acid as a novel, effective therapeutic agent.
However, to our present knowledge, there is a scarcity of studies
evaluating the impact of ferulic acid on photoaging skin. The aim of
this study is to evaluate the effect of ferulic acid on skin hydration,
topography, the level of melanin, and the severity of erythema, in peo-
ple with skin photoaging symptoms.
2|MATERIAL AND METHODS
2.1 |Patient selection
The study included a group of 20 patients aged 45–60, with the II and
III skin phototypes according to Fitzpatrick's scales. Clinical evaluation
of photoaging was done according to Glogau Wrinkle Scale. Fourteen
patients were classified as moderate (II type) and six patients as
severe (IV type) facial photoaging. Before starting the examination, a
detailed interview with each of the patients was conducted. It reg-
arded general health, including information about taken medicines
and skin diseases. The patients were qualified for the examination and
then instructed about skin care regimen after the treatments. All
patients pledged to comply with the recommendations and to resign
from other cosmetic and dermatological procedures for the entire
duration of the study. Each of the patients completed a full cycle of
2.2 |Treatment protocol
Each patient received a series of eight treatments of chemical peeling
based on 14% ferulic acid (Mediderma by Sesderma
once a week. This product contains ferulic acid (in nanosome
technology) and propylene glycol. Before applying ferulic peeling, the
skin was cleaned with the make-up cleansing milk and then degreased
with disinfectant spray based on ethyl alcohol. Next, a special product
containing empty nanosomes was sprayed on the face, to enhance
the transepidermal permeation of active ingredients. Afterward, in a
few minutes intervals, two layers of peeling were applied to the skin.
A total of 1.5 ml. Each layer, in accordance with the producer's recom-
mendations, was massaged into the skin until absorbed. Next, patients
were asked to wash their faces at home 6 h after the treatment, using
a cotton pad soaked in lukewarm water, as the nanosome products
had to be left on the skin for a couple of hours. Patients were
instructed to use only delicate, moisturizing cream and apply sun-
screen with a high Sun Protection Factor (SPF 50) every morning.
Measurements of selected skin parameters were made with
Mexameter (melanin and erythema level) and Corneometer (skin
hydration level)—The Multi Probe Adapter (MPA) Systems
(Courage +Khazaka electronic GmbH, Köln, Germany). The measure-
ments included 3-time points: before starting a series of treatments,
immediately after the end of the series (8 weeks after the first treat-
ment), and 1 month after the end of the series (12 weeks after the
first treatment). Three measurement points were designated: 1—on
the forehead, 2—on the cheek, and 3—on the jaw. The untreated skin
sample behind the ear constituted a control point (point 4), as it is the
nearest and most similar skin area to the treated one. All measure-
ments were done three times in each place and the recorded result is
All measurements were made in the same room, with constant
temperature conditions (24–26C) and air humidity (33%–41%),
always at a similar time of the day. Before taking the measurements,
the patients were asked for 10–15 min acclimatization in the
Mexameter MX 18 (Courage +Khazaka electronic) it is a non-
invasive device used to measure the concentration of melanin and
hemoglobin in the skin by light absorption. The probe emits light at
three wavelengths selected to achieve different levels of absorption
by the pigment melanin (MEX) and hemoglobin (ERYT). The amount of
light emitted is precisely defined, the amount of light absorbed by the
skin can be calculated and the receptor measures the light reflected
from the skin. Melanin and erythema index were calculated.
Skin hydration was measured with Corneometer CM825, which
measurement of skin's electrical capacity, based on the relatively high
dielectric constant of water. It is related to the degree of epidermal
hydration. Parameters used: skin compressed for 1 s with a force of
,20–30 μm deep into the stratum corneum. The measure-
ment result is in the range 0–130. The higher is the value, the better
is the hydration of the epidermis.
The topography of the skin was accurately examined with Vis-
VC 98 (Courage +Khazaka electronic GmbH, Köln,
Germany)—a high-resolution UVA camera. The photographs show the
FIGURE 1 Chemical structure of ferulic acid
2of8 ZDUŃSKA-PĘCIAK ET AL.
structure of the skin in multiple magnifications. The SELS
(Surface Evaluation of the Living Skin), developed especially for this cam-
era are SEsc (scaliness)—a value expressed in arbitrary units, showing the
level of exfoliation of the stratum corneum, including the value of hydra-
tion and SEr—skin roughness. Both values increase with age.
Additionally, before starting the treatment and after its comple-
tion, photographs were taken with photographic systems: VISIA
Complexion Analysis System (Canfield Scientific, Inc.) and
The results are presented as mean value and standard deviation
(SD) mean ± SD. Repeated measures one-way analysis of variance
(ANOVA) (with a Greenhouse–Geisser correction where appropriate)
followed by Bonferroni's post hoc comparisons tests were used.
3.1 |Skin lightening efficacy
A statistically significant difference in skin melanin level was observed
in all measuring points, directly after a series of treatments. The
decrease of melanin level was slightly greater on the forehead and on
the jaw than on the cheek area (p< 0.0001 and p< 0.001, respec-
tively) (Figure 2). The last measurement, taken a month after the end
of the series, showed still a significant improvement on the forehead
and jaw, compared to the baseline (p< 0.0001). On the cheek, the
level of melanin raised almost to the baseline a month after the series
3.2 |Anti-redness efficacy
At the end of the series, the intensity of erythema decreased signifi-
cantly in all measuring points, showing slightly greater efficacy on the
forehead (p< 0.0001) than on the cheek and jawline (p< 0.05). A
month after the series of treatments the improvement was even bet-
ter, showing statistical significance of p< 0.0001 on the forehead and
p< 0.001 on the cheek and jaw areas (Figure 3).
3.3 |Skin hydrating efficacy
A statistically significant difference in skin hydration level was
observed in all measuring points, directly after a series of treatments
(p< 0.0001). A month after the end of the series, hydration decreased
slightly, compared to the second measurement, still showing the sta-
tistically significant difference to the baseline (p< 0.0001 on the
cheek and jaw and p< 0.001 on the forehead) (Figure 4).
3.4 |Skin smoothing efficacy
Statistically significant reduction of exfoliation (SEsc) and roughness
(SEr) of the epidermis, was observed on the forehead and jaw
(p< 0.05) (Table 1).
At the control, untreated point none of the probes showed statis-
tically significant changes (Table 2).
Throughout the duration of the study, none of the patients' side
effects were noted in the form of irritation, burning, redness of the
skin, which proves the safety of using ferulic acid in the form of chem-
Photoaging of the skin is a process that affects both: the epidermis
and the dermis. Histologically, in the epidermis, it concerns its thicken-
ing and alterations within its cells (i.e. melanocytes and Langerhans
cells). However, major changes are observed in the dermis and they
relate to the elastosis process, the invalid structure of collagen fibers,
changes in the number of proteoglycans, glycosaminoglycans, and
Therefore, for the treatment of photoaging skin, a
substance that penetrates into the deeper tissue is needed.
acid has been shown to penetrate deeply into the skin, both acidic
and neutral pH, in dissociated and non-dissociated forms. Its effi-
ciency is closely related to maintaining a high local concentration and
low cutaneous metabolism.
This study demonstrated, that ferulic acid peel is an effective
therapeutic agent in reducing clinical signs of photoaging such as skin
dryness, telangiectasia, erythema, and hyperpigmentation. The results
achieved by MPA probes (Mexameter and Cutometer) are reflected
by photo documentation (Figures 5and 6).
FIGURE 2 Melanin value according to place and time of
measurement. White bar—measurement I, light gray bar—
measurement II, dark gray bar—measurement III. Data presented as
mean ± SD. ***p< 0.0001; **p< 0.01 versus measurement I;
##p< 0.01; #p< 0.05 versus measurement II
ZDUŃSKA-PĘCIAK ET AL.3of8
Ferulic acid is a well-known compound in the pharmaceutical,
food, and cosmetic industries. It is widely used as a preservative,
and vitamin stabilizer.
Its strong antioxi-
dant activity is related to free radical scavenging,
that catalyze free radical generation,
binding transition metals,
preventing lipid peroxidation, enhancing other scavenger enzymes
Ferulic acid shows an antioxidant activity due to the phenolic ring
and unsaturated side chain.
It has the capacity to inhibit a complex
reaction of free radicals generation, by forming stable phenoxyl radi-
cals, in the reaction of the radical molecule with the molecule of anti-
oxidant. The phenoxy radical is formed, which is highly resonance
stabilized, so it ends its life in condensation and collision with another
ferulate radical. It has also the ability to donate atoms directly to the
radicals, acting as a hydrogen donor. Another antioxidant mechanism,
associated with binding transition metals such as iron and copper, pre-
vents the formation of toxic hydroxyl radicals and in the aftermath
autoxidation of lipid acids cell membrane.
Ferulic acid has the
ability to inhibit enzymes that catalyze the formation of free radicals
and of strengthening scavenger radical enzymes.
Milani et al.
showed skin protective effects of an antioxidant
and antipollution serum with Deschampsia antartica extract, ferulic
acid, and vitamin C. The study was conducted on a group of 20 women
living in an area of high pollution urban area. The study showed
improvement of skin barrier function, to counteract the skin oxidative
stress and to reduce hiperpigmentations.
In our research, nanosomal formulations were used (nanosome
technology). Gupta et al.
states that ferulic acid has problems of
poor stability and low aqueous solubility in cosmetics products. The
solution obtained in the research was suggested to be an optimal con-
centration (0.5 wt% ferulic acid in bulk solution) for successful nano-
emulsion formulation. In the study formulations of ferulic acid-loaded
lipid-based nanoparticle systems, can find various uses in cosmetics.
FIGURE 3 Erythema value according to place and time of
measurement. White bar—measurement I, light gray bar—
measurement II, dark gray bar—measurement III. Data presented as
mean ± SD. ***p< 0.0001; **p< 0.01; *p< 0.05 versus measurement
I; #p< 0.05 versus measurement II
FIGURE 4 Skin hydration level according to place and time of
measurement. White bar—measurement I, light gray bar—
measurement II, dark gray bar—measurement III. Data presented as
mean ± SD. ***p< 0.0001; **p< 0.01 versus measurement I
TABLE 1 Visioscan parameters values: exfoliation (SEsc) and
roughness of the epidermis (SEr)
Parameter Measurement 1 Measurement 2 Significance
SEr 2.98 ± 1.06 2.39 ± 0.82 p=0.151
SEsc 0.45 ± 0.10 0.35 ± 0.07 p=0.031*
SEr 3.87 ± 0.66 2.52 ± 0.18 p=0.103
SEsc 0.54 ± 0.13 0.42 ± 0.06 p=0.115
SEr 3.42 ± 0.82 2.35 ± 0.54 p=0.027*
SEsc 0.49 ± 0.05 0.40 ± 0.11 p=0.175
Note: Data presented as mean ± SD. Values of both parameters (Sesc and
Ser) increase with age.
TABLE 2 Control point
parameter's values according to the time
Parameter Measurement 1 Measurement 2 Significance
Melanin 162.3 ± 42.6 159.8 ± 44.7 p=0.271
Erythema 350.1 ± 64.6 349.6 ± 62.1 p=0.368
Corneometer 55.9 ± 13.5 53.2 ± 11.1 p=0.162
PK Vser 1.14 ± 0.19 1.14 ± 0.21 p=0.739
PK Vsesc 0.57 ± 0.12 0.59 ± 0.11 p=0.383
Note: Data presented as mean ± SD.
4of8 ZDUŃSKA-PĘCIAK ET AL.
Das and Wong researched to stabilize ferulic acid in topical hydrogel
formulation via nanoencapsulation technique and low pH (less than
pKa of ferulic acid). They proved that products with ferulic acid with
low pH can maintain skin microbiome and homeostasis, may pene-
trate into skin layers (avoid systemic circulation).
Further pre-treatment studies confirmed the great photoprotective
ability of ferulic acid-loaded multiple emulsions (MA), in fact, following a
5 h pre-treatment with ME (W/O/W multiple emulsions), the skin of the
volunteers become more protected from a subsequent physical insult
and the erythema index remained on lower values than those of the sites
pre-treated with the other formulations.
As a result of excessive free radical reactions, the functioning of
the skin is disturbed and aging is accelerated. Skin becomes
dehydrated, sagging, wrinkled, appears discoloration and vascular spi-
der veins. Treatment with ferulic acid counteracts photoaging of the
skin, and also shows depigmenting properties, controlling tyrosinase
activity. Because FA has a similar structure to tyrosine, it is believed
that it inhibits melanogenesis through competitive inhibition with
tyrosine. What else, vitamin E ferulic acid ester exhibited an inhibitory
effect on melanin production.
In this research series of treatments with ferulic acid peel, caused
a decrease of skin melanin content and thus brightening and evening
FIGURE 5 Lightening activity of
ferulic acid. I photograph—before, II
photograph—after the treatment session.
Women age 48. II type according to
Glogau Wrinkle Scale. The level of
melanin at the baseline: 175. The level of
melanin after the eight treatments of FA
FIGURE 6 The cutaneous superficial
network of blood vessels. I photograph—
before, II photograph—after the treatment
session. The photograph taken by VISIA
Canfield Scientific showing the number
and size of vascular lesions. Made in cross
polarity in RBX
technology. Women age
58. II type according to Glogau Wrinkle
Scale. The level of erythema at the
baseline: 470. The level of erythema after
the 8 treatment of FA peel: 385
ZDUŃSKA-PĘCIAK ET AL.5of8
of skin color. Minor hyperpigmentation has also been lightened and
much less visible (Figure 5). Park et al. investigated the mechanism of
the skin-whitening action of ferulic acid. It is based on the inhibition
of intracellular tyrosinase synthesis in melanocytes. The synthesis of
melanin is suppressed by reducing the expression of microphthalmia
transcription factor (MITF)—a major transcriptional regulator of the
genes for tyrosinase. Ferulic acid affects the synthesis and decomposi-
tion of the melanogenic enzyme, by controlling the activity of its tran-
scription factor. Park et al.
in their study on B16F10 mouse
melanoma cells showed a 19.1% decrease in intracellular tyrosine syn-
thesis, after exposure to 20 μg/ml ferulic acid. The intensity of the
melanin synthesis process decreased by 43.6%. Dayal et al.
study comparing the efficacy of 12% ferulic acid peel with two other
common peels, noted good to excellent improvement (according to
physician global assessment) in the intensity of periorbital hyper-
pigmentation (POH) in almost half of the FA group. What is more,
12% ferulic acid was the best-tolerated peel among the three.
Importantly, the effects achieved during a series of ferulic acid
treatments persist over time. A month after the end of the series of
treatments, the amount of melanin in the skin increased slightly, still
showing a significant improvement, compared to the baseline. This
may be related to the preventive role of ferulic acid, against changes
in the skin caused by UVA and UVB radiation. Pluemsamran et al.
proved that there are much smaller photodamages in keratinocytes if
ferulic acid is administered prior to UV radiation. Reactive oxygen spe-
cies' production decreases significantly, endogenous antioxidants, that
is, glutathione, and catalase undergo a smaller reduction, and their
level returns to the state before exposure. Upon absorption of UV,
phenol acids catalyze the stable phenoxy radical formation, ferulic acid
terminating free radical chain reactions. Therefore, it can be assumed
that ferulic acid not only reduces already existing signs of photoaging
but also prevent future photodamage in the skin.
Murray et al.
have demonstrated that a stable topical formula-
tion of 15% L-ascorbic acid, 1% alphatocopherol, and 0.5% ferulic acid
(CEFer) is able to significantly decrease the expression of immunosup-
pressive and proinflammatory cytokines that occurs with UV damage.
CEFer was applied to separate patches of human skin for 4 days and
next the skin was irradiated UV.
Mancuso et al.
conducted in vivo and in vitro research which
the aim was the evaluation of three types of emulsions with ferulic
acid. MA showed the best ability to carry and release ferulic acid and
great stability. What is important, in vivo investigation showed that
MA has the best capability to treat UV-B-induced erythema.
The study demonstrated that therapy with ferulic acid peel reduced
the severity of erythema and visibility of telangiectasia. The best results
were achieved on the forehead and cheeks, which is confirmed by the
photo taken with the VISIA
, illustrating the cutaneous superficial net-
work of blood vessels (Figure 6). Literature data indicate that ferulic acid
has been used for a long time in neurodegenerative and circulatory sys-
tem diseases. It also improves blood circulation, prevents thrombocyte
clumping, and has antithrombotic properties.
Lin et al.
research on human umbilical vein endothelial cells (HUVEC), demon-
strated that ferulic acid induces the expression of major angiogenic regu-
latory factors: vascular endothelial growth factor (VEGF) and platelet-
derived growth factor (PDGF). It also increases the amount of hypoxia-
inducible factor 1 (HIF-1)—a factor that generates a response to hypoxia.
Treatment with ferulic acid leads to significant induction of VEGF, PDGF,
and HIF-1αmRNA and protein expression, in a concentration-dependent
and time-dependent manner. Due to the angiogenic effect, ferulic acid is
supposed to be a new therapeutic agent for microcirculation disorders,
also within the skin.
Ferulic acid also significantly increases skin hydration. The
increase in hydration of the stratum corneum results in its smoothing,
which was confirmed by the photos taken with Visioscan (Figure 7).
Chiu et al.
demonstrated that topically applied antioxidants reduce
transepidermal water loss, support the hydro-lipid barrier, contributing
to the increase of water content in the epidermis. What is more, with
several applications, they have the ability to cumulate in the epidermis
and dermis. In order to achieve optimal results, antioxidant com-
pounds should be used relatively frequently and regularly, which con-
firms the legitimacy of performing treatments with ferulic acid in the
series. Kanlayavattanakul et al.
noted satisfactory effects in the form
of improved hydration of the epidermis, after using a rice extract-rich
in phenolic compounds, including ferulic acid. After 2 months of using
the cream with rice extract, the level of hydration of the epidermis
increased almost 2-times.
FIGURE 7 Skin surface in a multiple
magnification. I photograph—before, II
photograph—after the treatment session.
The photograph taken by Visioscan
VC98 showing the skin topography using
a special UV-A light video camera with
high resolution. The images show the
structure of the skin and the level of
dryness. Accurate analysis of the skin is
made with the use of SELS
(Surface Evaluation of the Living Skin)
6of8 ZDUŃSKA-PĘCIAK ET AL.
The topical administration of ferulic acid could ensure activity against
An objective examination with the use of MPA probes—Mexameter
and Corneometer, showed a significant whitening, moisturizing and
erythema-reducing effect. The results achieved with apparatus, are
reflected in photographic documentation. Within the limits of our study,
we found the series of ferulic acid peel treatments, which seems to bring
promising effects on photoaging skin. Nevertheless, these initial results
need to be further validated on a larger sample size.
nska-Pęciak Kamila is responsible for the study design, collecting
the results, statistical analysis, preparing the preliminary version of the
manuscript. Dębowska Renata contributed to the collection of results
and photodocumentation. Anna Kołodziejczak checked and edited the
article in terms of content. Rotsztejn Helena has made an assessment
of the overall study design and the correctness of the draft of the
This work was supported by statutory research activity of the Depart-
ment of Cosmetology and Aesthetic Dermatology, Faculty of Phar-
macy, Medical University of Lodz, No. 503/3-066-01/503-31-001
and Grant/Award number 502-03/3-066-01/502-34-102.
Statutory research activity of the Department of Cosmetology and
Aesthetic Dermatology, Faculty of Pharmacy, Medical University of
Lodz, No. 503/3-066-01/503-31-001. Medical University of Ł
Grant/Award Number: 502-03/3-066-01/502-34-102.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
All participants have given their written informed consent to the pro-
cedure. The study protocol has been approved by the Bioethics Com-
mittee of the Medical University of Lodz (Protocol No. RNN/81/19/
KE). All procedures involving human probands were in accordance
with the ethical standards of the institutional and/or national research
committee and with the 1964 Helsinki declaration and its later
amendments or comparable ethical standards.
Anna Kołodziejczak https://orcid.org/0000-0002-7799-9188
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How to cite this article: Zdu
nska-Pęciak K, Dębowska R,
Kołodziejczak A, Rotsztejn H. Ferulic acid –A novel topical
agent in reducing signs of photoaging. Dermatologic Therapy.
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