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Ferulic acid – A novel topical agent in reducing signs of photoaging


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Introduction: 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. Methods: 20 women aged 45 to 60, received 8 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) and VISIA® Complexion Analysis System (Canfield Scientific, Inc.). Results The objective evaluation 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. Conclusion: 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.
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Ferulic acid A novel topical agent in reducing signs of
Kamila Zdu
| Renata Dębowska
| Anna Kołodziejczak
Helena Rotsztejn
Department of Cosmetology and Aesthetic
Dermatology, Faculty of Pharmacy, Medical
University of Ł
z, Ł
z, Poland
Centre for Science and Research Dr Irena
Eris, Warsaw, Poland
Kamila Zdu
nska-Pęciak, Department of
Cosmetology and Aesthetic Dermatology,
Faculty of Pharmacy, Medical University of
z, Muszy
nskiego 1 Street, PL-91-151 Ł
Funding information
Medical University of Ł
odz, Grant/Award
Numbers: 503/3-066-01/503-31-001,
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 4560, 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
DOI: 10.1111/dth.15543
Dermatologic Therapy. 2022;e15543. © 2022 Wiley Periodicals LLC. 1of8
function as an antioxidant in sunburn cells. Ferulic acid is able to
absorb UVA (cis-ferulic acidpeak 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.
2.1 |Patient selection
The study included a group of 20 patients aged 4560, 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
), performed
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.
2.3 |Measurement
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: 1on
the forehead, 2on the cheek, and 3on 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
their average.
All measurements were made in the same room, with constant
temperature conditions (2426C) and air humidity (33%41%),
always at a similar time of the day. Before taking the measurements,
the patients were asked for 1015 min acclimatization in the
measuring room.
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
7.1 N/cm
,2030 μm deep into the stratum corneum. The measure-
ment result is in the range 0130. 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
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 SErskin 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
Fotomedicus (Elfo
The results are presented as mean value and standard deviation
(SD) mean ± SD. Repeated measures one-way analysis of variance
(ANOVA) (with a GreenhouseGeisser 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
of treatments.
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-
ical peeling.
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
inflammatory cells.
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 barmeasurement I, light gray bar
measurement II, dark gray barmeasurement III. Data presented as
mean ± SD. ***p< 0.0001; **p< 0.01 versus measurement I;
##p< 0.01; #p< 0.05 versus measurement II
Ferulic acid is a well-known compound in the pharmaceutical,
food, and cosmetic industries. It is widely used as a preservative,
photoprotective agent,
and vitamin stabilizer.
Its strong antioxi-
dant activity is related to free radical scavenging,
inhibiting enzymes
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 barmeasurement I, light gray bar
measurement II, dark gray barmeasurement 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 barmeasurement I, light gray bar
measurement II, dark gray barmeasurement 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.
*p< 0.05.
TABLE 2 Control point
parameter's values according to the time
of measurement
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.
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 photographbefore, II
photographafter 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
peel: 133
FIGURE 6 The cutaneous superficial
network of blood vessels. I photograph
before, II photographafter 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
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.
in their
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.
in their
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 photographbefore, II
photographafter 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)
The topical administration of ferulic acid could ensure activity against
UV-induced photodamage.
An objective examination with the use of MPA probesMexameter
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.
The authors have no conflicts of interest to declare.
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.
Kamila Zdu
Anna Kołodziejczak
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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.
2022;e15543. doi:10.1111/dth.15543
... They grouped 20 women between the ages of 45 and 60 receiving 8 regimens and assessed skin hydration, melanin levels and erythema level moisturizing activity. Based on the findings, the authors concluded that the therapy sequence shows remarkable results in skin parameters [155]. In addition, Nicolau et al. aimed to determine the effectiveness of FA in freshly sliced apples and melons in terms of its antimicrobial activity and preservation of fruit quality when stored at concentrations in the range of 2.515 g L1 versus L. monocytogenes and S. Enterika. ...
... Increased skin hydration and decreased melanin contents [155] Antimicrobial FA preserved the quality of the fruits (pH, total soluble solids, and titratable acidity) via immersion method [156] Anti-biofilm property FA has multiple phenotypic and molecular responses of S. Enteritidis [157] Anti-diabetic effects Declined lipid and glucose metabolism due to increased AMP and ATP via AMPK phosphorylation [158] Photoaging Enhanced skin elasticity and antioxidant potential [159] Colorectal cancer Declined inflammatory markers and selfmodulated programmed cell death [160] Dietary effects Best growth performance and feed efficiency, higher transcriptional levels of immune-related genes, declined apoptosisrelated genes (Caspase-3 and p53) and keap1b expression [161] Reduced Nephrotoxicity Reduced oxidative stress and increased antioxidant and anti-inflammatory power [162] Diabetes induced foot ulcer Declined cell toxicity for HaCaT cell lines, improved wound healing and skin restorative power [163] D. Shukla et al. ...
Approximately 40% and 90% of the drugs developed and in the developing phase, suffer from poor aqueous solubility, and thereby exhibiting declined oral bioavailability and restricted enteric permeability. Phenolic compounds comprise a collection of phytochemicals, possessing low water solubility, thus limiting their clinical applications. This makes them a classical contender for thorough analysis and application in formulation development. It exhibits several useful pharmacological activities including anti-inflammatory, antioxidant, anticancer, and neuroprotective. Even though preclinical, clinical, and FDA approval describe the advantages and credibility of trans-ferulic acid; its medicinal applicability as a therapeutic compound is finite owing to low solubility and bioavailability. Nanotechnology-based formulation development scheme is generally applied to overcome biopharmaceutical drawbacks of hydrophobic drugs. The principal objective of this manuscript is to present a review of conventional and novel synthesis mechanisms, structural activity relationship, physicochemical properties, and anticancer impacts of ferulic acid. Finally, we have reviewed various emerging and advanced formulations of ferulic acid. We hope that this review would offer an opportunity for formulation scientists to bridge the preclinical and clinical gaps.
... Some experiments performed on diabetic rats have shown that ferulic acid accelerates wound healing (Ghaisas et al. 2014;Bairagi et al. 2018). In addition, it provides a whitening, moisturizing and erythema reduction effect, being considered a promising active in formulations for topical application (Zduńska-Pęciak et al. 2022). The compounds identified here were previously detected in the species (Pires et al. 2021b) and found in the characterization of other species belonging to the Acanthaceae family (Cassola et al. 2019;Basit et al. 2022). ...
Ruellia angustiflora is a shrub popularly known as flower of fire, used in traditional medicine as a healing agent. This study aims to verify the presence of characteristics of pharmaceutical interest in extracts from the root, stem and leaves of this species. The ideal time for ultrasound-assisted extraction is 60 min with a solid-liquid ratio of 1% (w/v). The kinetics of the reaction of the extracts with DPPH is biphasic, and IC50 values are related to the total phenolic compounds. Five phenolic compounds were identified in the extracts, where ferulic acid, rutin and quercetin showed to be the main responsible for the antiradical activity. The extracts displayed considerable photoprotective activity, mainly Ra-LE (SPF = 23). Ra-RE showed an inhibition halo similar to erythromycin against Streptococcus pyogenes. Taken together, these data reveal that Ruellia angustiflora is a source of phenolic compounds and has relevant antiradical, photoprotective and antibacterial activities.
... It is known for its ability to capture high-resolution images and analyze facial skin parameters simultaneously. 5,7 On the other hand, YLGTD is a newer mobile software developed by Hangzhou C2H4 Internet Technology Co, Ltd., China, which uses image processing techniques to analyze and evaluate user skin through smartphone-based images. ...
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Background: Erythema, characterized by redness of the skin, is a common symptom in various facial skin conditions. Recent advancements in image processing and analysis techniques have led to the development of methods for analyzing and assessing skin texture. This study aimed to investigate the correlation between the parameters of "You Look Good Today" (YLGTD) and VISIA in the detection and assessment of facial redness. Materials and methods: Thirty female subjects participated in this experiment, undergoing assessments using both YLGTD and VISIA. The subjects were evaluated for facial redness, and the feature count results within the red zone were measured by VISIA. YLGTD analyzed the number and percentage of red zone pixels. The assessments were conducted between [specific dates] in [location]. Results: The results demonstrated a significant positive correlation between the feature count results within the red zone measured by VISIA and the number of red zone pixels. Similarly, YLGTD exhibited a significant positive correlation with the number and percentage of red zone pixels. Conclusion: In conclusion, our findings suggest a correlation between YLGTD and VISIA in the measurement of facial erythema. YLGTD can serve as a portable device for primary screening assessments, offering a convenient and reliable method to evaluate facial redness. This research contributes to the development of non-invasive techniques for assessing and monitoring facial skin conditions, providing valuable insights for dermatological diagnosis and cosmetic testing.
... It efficiently alleviates the negative effects of UVinduced oxidative stress [93,94]. In vivo studies have confirmed ferulic acid skin firming, moisturizing, and pigmentation regulating activity [95]. ...
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Aromatic and medicinal plants are a great source of useful bioactive compounds for use in cosmetics, drugs, and dietary supplements. This study investigated the potential of using supercritical fluid extracts obtained from Matricaria chamomilla white ray florets, a kind of industrial herbal byproduct, as a source of bioactive cosmetic ingredients. Response surface methodology to optimize the supercritical fluid extraction process by analyzing the impact of pressure and temperature on yield and the main bioactive compound groups were used. High-throughput 96-well plate spectrophotometric methods were used to analyze the extracts for total phenols, flavonoids, tannins, and sugars, as well as their antioxidant capacity. Gas chromatography and liquid chromatography–mass spectrometry was used to determine the phytochemical composition of the extracts. The extracts were also analyzed for antimicrobial activity, cytotoxicity, phototoxicity, and melanin content. Statistical analysis was performed to establish correlations between the extracts and develop models to predict the targeted phytochemical recovery and chemical and biological activities. The results show that the extracts contained a diverse range of phytochemical classes and had cytotoxic, proliferation-reducing, and antimicrobial activities, making them potentially useful in cosmetic formulations. This study provides valuable insights for further research on the uses and mechanisms of action of these extracts.
This study evaluated dentin enzymatic degradation based on the total matrix metalloproteinase (MMP) activity of demineralized dentin matrices before and after exposure to phosphoric acid (PA), glycolic acid (GA), and ferulic acid (FA). The release of hydroxyproline (HP), ultimate tensile strength (UTS), and dentin permeability (DP) were also evaluated. Dentin collagen matrices were assessed according to total MMP activity before and after treatment with the tested acids (n=10) for 15 seconds and compared with the control (GM6001 inhibitor). Dentin beams were analyzed for HP release and UTS after the treatments. Dentin discs were tested for DP at a pressure of 5 psi before and after treatment with the acids (n=10). The FA group had a lower percentage of enzymatic inhibition than the PA and GA groups (p<0.0001). No significant difference in UTS was found among the acids (p=0.6824), but HP release was significantly higher in the FA group than in the PA and GA groups (p<0.0001). No significant difference in DP was found for the acids (p=0.0535). GA led to less activation of MMPs and less release of HP, whereas the UTS and DP for GA were like those found for PA. In contrast, FA promoted greater enzymatic activity and greater release of HP, while having similar results to GA and PA regarding mechanical properties.
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Ferulic acid is a derivative of cinnamic acid showing efficacious anti-oxidant activity. It catalyzes the stable phenoxy radical formation, upon absorption of ultraviolet light, giving the strength to ferulic acid for terminating free radical chain reactions. Ultraviolet rays are one of the most dangerous factors that daily assault the skin, causing excessive generation of reactive oxygen species (ROS), which are regarded to be important contributors to a variety of cutaneous alterations. The skin possesses endogenous antioxidant defense systems, but the excess of ROS leads to an oxidant-antioxidant imbalance. Although ferulic acid is daily introduced in human organism with the diet, its bioavailability after oral administration is poor, particularly in the skin. The aim of this investigation was to evaluate three types of emulsions (W/O/W multiple emulsions and two simple emulsions) as suitable formulations for topical application of the active compound. In vitro studies were performed to investigate the stability and release profiles of these systems. Multiple emulsions showed great stability and the best ability to carry and release ferulic acid. In vivo evaluations highlighted their best capability to treat UV-B-induced erythema. These findings suggested multiple emulsions as an innovative and more efficient vehicle for topical application of ferulic acid.
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Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry‐based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose‐dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin‐nicotinamide (STZ‐NA)‐induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.
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Abstract Ferulic acid is a potent anti-oxidant with scientifically proven skin care efficacies. However, instability of this active in the skin care products restricted its wide application in beauty and skin care industries. This study aimed to stabilize ferulic acid in topical hydrogel formulation via nanoencapsulation technique. Ferulic acid loaded nanocapsules were prepared via high pressure homogenization method and physicochemically characterized. Mean particle size of ferulic acid loaded nanocapsules was
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A new method to stabilize ferulic acid (FA) in the aqueous phase by encapsulating FA into β-cyclodextrin was developed to prepare ferulic acid-β-cyclodextrin inclusion complexes (FCICs), and the potential applications of FCIC as a preservative in hairtail (Trichiurus lepturus) were tested. The antibacterial properties of specific spoilage bacteria in hairtail were analyzed. FCIC possessed significantly higher efficacy (p < .05) of scavenging DPPH and H2O2 radicals. In the antibacterial assessment, several strains isolated from hairtail after ten days of storage were selected. FCIC showed significantly higher antibacterial activities (p < .05) against these bacteria. To further validate whether the antioxidant and antibacterial activities of hairtail remained throughout storage, the physiological properties of hairtail were analyzed. It was shown that hairtailtreatment with FCIC inhibited the spoilage of hairtail throughout storage at 4°C. FCIC with an FA:β-CD ratio of 1:2 (IC1:2) could prolong the shelf life of refrigerated hairtail for 3–5 days. This study provided an enormous potential for applying FA in the shelf-life extension of hairtail.
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Introduction: Air pollution causes skin damage and favors skin aging processes such as dark spots and wrinkles, through oxidative stress. Pollutant substances accelerate skin aging through a specific activation of intracellular receptors called AhR (aryl-hydrocarbon receptors). Deschampsia antartica aqueous extract (DAE) has shown to counteract the pollutant-induced AhR activation. Ferulic acid (FA) and vitamin C (VC) are potent antioxidant substances. A serum containing DAE/FA/VC has been recently developed. So far, no clinical data are available regarding the protective actions of this serum against the detrimental effects of air pollution on the skin. Objective: We conducted a prospective, single-blind, 28-day study to assess efficacy and protective effects against air pollution skin damage of a new serum containing Deschampsia antartica extract. Materials and methods: Twenty, photo type I-III, women (mean age 42 years) with at least three dark spots on the face, living in a homogenous urbanized, high pollution area (Rome) were evaluated. The objectives of the study were to evaluate the effects of treatment on skin barrier function, assessed by transepidermal water loss (TEWL) measurement (Tewameter), the effect on dark spots, evaluated by means of colorimetry (Colorimeter CL 400), and the effect on squalene peroxide (SQOOH)/squalene (SQ) skin ratio assessed with face swabs. Results: The trial was conducted between November 20 and December 19, 2018. In comparison with baseline, the product induced a significant improvement of skin hydration (-19% of TEWL), a significant improvement of dark spots (+7%) and a significant improvement of SQOOH/SQ ratio (-16%). The product was evaluated very well by >90% of the treated subjects regarding cosmetic acceptability. Discussion: A serum containing DAE/FA/VC has shown to improve skin barrier function, to reduce dark spots and to counteract the skin oxidative stress in women living in high pollution urban area.
Ferulic acid, though used in formulations of skin-care and cosmetic products, suffers from the problems of poor stability and low aqueous solubility. Encapsulation into nanoparticle can be a viable route to overcome these inherent problems. In this proof-of-concept, we combine experimental studies and molecular dynamics (MD) simulations to provide insights into the underlying formation mechanism of ferulic acid-loaded lipid based nanoemulsion and nanoparticle formulations in aqueous environment. This experimental-cum-simulation study provides molecular-level understanding into lipid-active nanoparticle system; and would assist the design and optimization of formulation systems for skin-care/cosmetic/pharmaceutical applications. The examined lipid is Gelucire® 50/13, which is selected due to higher solubility of ferulic acid in molten Gelucire® 50/13 in compare to other tested lipids. Experimental results show the successful formation of nanoemulsion and subsequently nanoparticle in water with 0.5 wt% ferulic acid. While providing useful insights into structural, energetic, and dynamical properties of nanoemulsion/nanoparticle, MD simulations demonstrate that ferulic acid molecules are present at the surface layer of the nanoparticle whereas hydrophobic parts of lipid molecules exist in the core and hydrophilic parts at the surface of the nanoparticle. The nanoemulsion is originated by quick assembly of lipid molecules into many small nuclei which latter aggregate into larger clusters of spherical shape. During cooling, the shape and size of the nanoparticle are found to be unchanged, but dynamics/mobility of the nanoparticle as well as ferulic acid reduced significantly due to solidification. Additionally, higher concentrations of ferulic acid (1 wt% or 5 wt%) lead to either the existence of un-encapsulated ferulic acid in bulk or the destabilization of the nanoparticle structure – validated by experiments. Hence, the optimal concentration of ferulic acid for successful formation of nanoparticle is 0.5 wt%. Ferulic acid loaded nanoparticle can be useful for skin-care/cosmetics products.
Background Aqueous formulations of vitamin C stabilized by vitamin E and ferulic acid at low pH effectively protect skin against reactive oxygen species‐induced damage. However, the effects of these formulations on human skin have not clearly been described. The aim of this study was to investigate whether topical application of two commercially available formulations of vitamin C alter human skin using an ex vivo model. Methods Human skin explants were topically treated on alternate days with commercially available formulation 1 (15% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline or formulation 2 (20% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline. Only saline was applied to control skin explants. Results Topical formulation 1 at 100%, 50%, or 10%, but not formulation 2 at 100%, 50%, or 10%, reduced the viability of ex vivo human skin compared to the control after 7, 10, and 13 days. In addition, compared to the control, ex vivo human skin treated with formulation 1 at 50%, but not formulation 2 at 50%, also decreased mRNA levels of actin and ribosomal protein L10 and gene expression of extracellular matrix components after 10 days. Furthermore, after 10 days, topical application of formulation 1 at 50%, but not formulation 2 at 50%, decreased the protein expression of proliferating cellular nuclear antigen, lysyl oxidase, β‐actin, and glyceraldehyde‐3‐phosphate dehydrogenase compared to the control. Conclusions Topical formulation 1, but not formulation 2, may reduce the viability of and protein synthesis in ex vivo human skin. Those effects might be due to action of vehicle of formulation 1 on ex vivo human skin.
Background: Periorbital hyperpigmentation (POH) is a very common, yet unexplored aesthetic condition. Topical therapy is mainstay of treatment which includes chemical peels and other depigmenting agents. Aims: To compare clinical efficacy, safety, and tolerability of 20% glycolic acid peels, 15% lactic acid peels, and 12% ferulic acid peels in the treatment of constitutional type of periorbital hyperpigmentation in Indian patients. Methods: Ninety patients of constitutional POH were enrolled for 12 weeks. They were divided into three groups of 30 each. In 1st group 20% glycolic acid peeling, in 2nd group 15% lactic acid peeling and in 3rd group 12% ferulic acid peeling sessions were performed at 3 weekly intervals. Clinical improvement was assessed objectively using POH grading, physician's and patient's global assessment, and patient's global tolerance. Results: Significant improvement in periorbital hyperpigmentation was noted in all the three groups. Physician and patient's global assessment was excellent with glycolic acid peel followed by ferulic acid peel and lactic acid peel. The incidence of side effects in the form of erythema and itching was maximum with glycolic acid followed by lactic acid and least with ferulic acid, which did not necessitate cessation of therapy. Conclusion: Glycolic acid produced the best results among the three peels; however, ferulic acid peel emerged as a safe and effective modality for the treatment of POH.
Ultraviolet (UV) radiation stimulates several injurious biological effects on cutaneous tissue, causing, for instance, photocarcinogenesis. Sunscreens are topical products designed to protect the skin against these harmful effects and their use must be encouraged. The addition of antioxidants, as ferulic acid (FA), a phenolic compound from the class of the hydroxycinnamic acids, in sunscreens could improve their sun protection factor (SPF) and prevent inflammatory reactions. Here, the clinical safety and efficacy of an association of ethylhexyl triazone and bis-ethylhexyloxyphenol methoxyphenyl triazine (UV filters) with ferulic acid were assessed. Samples had good skin biocompatibility and presented satisfactory safety profile, even in a sun-exposed condition. A synergic effect between the natural polyphenol and the UV filters was evidenced, as well as, FA increased in vivo SPF in 37% and the UVA protection factor (UVA-PF) in 26%. The in vivo data indicated that FA reinforced the broad-spectrum characteristic of the photoprotective formulations. Additionally, according to the results from the ex vivo antioxidant test, it is plausible to recommend adjustments on the ex vivo protocol to explicitly determine the positive effects of topical antioxidant ingredients applied over the skin. These results provided a new perspective for the development of multifunctional bioactive sunscreens using FA as a new platform.