p ISSN 2723-6927-e ISSN 2723-4339
The Effect of Topical 0.1% Pomegranate Extract (Punica
Granatum) on Trans Epidermal Water Loss (Tewl) and
Skin Ph Levels in Patients with a History of Atopic Dermatitis
Albert Fernandes1*, Retno Indar Widayati2,
Puguh Riyanto3
Section/KSM Dermatology Venereology and Aesthetics, University
Faculty of Medicine
Diponegoro,
Indonesia1
RSUP Dr. Kariadi
Semarang, Indonesia23
Email: [email protected]1*,[email protected]2, [email protected]3
Repairing the skin barrier with moisturizers is one of the five main
pillars of treating atopic dermatitis. Petrolatum is considered the gold
standard, but its consistency is too thick and oily making it less comfortable
to use. Moisturizers containing pomegranate extract (Punica granatum) can be an
alternative choice that is more comfortable to use. The effectiveness of this
pomegranate extract can be evaluated using TEWL and pH examinations which are
considered accurate indicators for changes in skin barrier conditions.
Effectiveness of topical administration of 0.1% pomegranate extract in reducing
TEWL and skin pH in sufferers with a history of AD.Single blind
randomized clinical trial with two parallel group pre and post design. 34 sufferers with a history of AD were randomly divided
into treatment groups (topical 0.1% pomegranate extract, 17 subjects)
and control group (topical 100% petrolatum, 17 subjects). Moisturizer was
applied twice daily to the volar area of the forearm for 4 weeks.
Both groups showed a significant decrease in TEWL after 4 weeks with a TEWL
delta of -5.2�2.31g/m2/hour (p<0.001) in the pomegranate extract group and-7.0�7.95g/m2/hour(p=0.003) in the petrolatum group.
There was no significant difference in TEWL reduction between the two study groups.The
pomegranate extract group showed a significant decrease in pH after 4 weeks
with a pH delta of -0.5�0.10(p<0.001),
while the petrolatum group actually showed a slight increase with a pH delta of0.0�0.59
(p=0.6). The pomegranate extract group showed a significantly greater decrease
in pH (p<0.001).Topical 0.1%
pomegranate extract is as effective as 100% petrolatum in reducing TEWL, but
more effective in lowering skin pH.
Keywords: Punica
granatum, pomegranate extract, TEWL, pH, atopic dermatitis
INTRODUCTION
Atopic dermatitis (AD) is one of the most
common types of chronic inflammatory skin disease globally, (Hay et al., 2014) with a reported prevalence of 15�25% in children and
1�10% in adults. (S�nchez-Alzate &
S�nchez-Torres, 2017) This chronic and recurrent disease can reduce the
sufferer's quality of life and increase the financial burden due to the
treatment costs that must be incurred, �So it is very
important to provide optimal therapy to control symptoms and prevent
exacerbations that affect daily activitie (Frazier & Bhardwaj,
2020).
The
etiology underlying AD is multifactorial and involves internal factors in the
form of atopy and mutations in the filagrin-producing
gene (FLG), accompanied by various external factors that can cause disruption
of the epidermal barrier. This complex interaction between various etiological
factors will cause disruption of the integrity and function of the epidermal
barrier, dysregulation of the local and systemic immune system, as well as
disruption and imbalance in the composition of the skin microbiome (Hrestak
et al., 2022). The combination of
these various mechanisms can ultimately increase transepidermal
water loss (TEWL) and reduce the water content of the stratum corneum, reduce
the production of natural skin moisturizing factors (NMF), trigger denaturation
of various important enzymes in the stratum corneum, increase skin pH, and
increase skin permeability to external antigens and pathogenic microbes. In
turn, a number of these conditions can also further aggravate skin barrier
damage, aggravate inflammatory conditions in the skin, and increase the
dominance of pathogenic microbes on the surface of the skin, resulting in a
vicious cycle that continues and further worsens the patient's skin condition
over time if no action is taken. to break the chain of pathogenesis of atopic
dermatitis (Rawlings
& Matts, 2005).
Efforts to improve and maintain optimal
function of the skin barrier are one of the five main pillars of AD management (Mathiasen et al., 2020). The use of moisturizing preparations that have
occlusive, humectant and emollient effects as maintenance therapy for people
with a history of AD can help improve the condition of the skin barrier and
prevent recurrence (Saeki et al., 2022). especially through its effect in reducing TEWL,
modifying skin pH, and improving the condition of the skin microbiome by
reducing the colonization of pathogenic bacteria, especially S. aureus, so that
it can help improve the structure and function of the skin barrier and overcome
the symptoms of atopic dermatitis (Kim & Leung, 2018).
Petrolatum
is a moisturizing preparation that is considered the gold standard for initial
therapy in AD sufferers because it can reduce TEWL and repair the skin barrier
effectively through its role as an occlusive agent, where petrolatum with a
minimum concentration of 5% is known to reduce TEWL by more than 98%.
Unfortunately, the use of petrolatum is generally not preferred because it has
several disadvantages, including the consistency being too thick and oily so it
is less comfortable to use, and it can stick and leave marks on clothes.
Therefore, it is necessary to consider the use of alternative moisturizers that
can be beneficial in improving the skin barrier without any undesirable effects
so that it can increase patient compliance in using moisturizers.
Nutraceutical
ingredients in the form of pomegranate extract (Punica granatum) which is rich
in various phytochemical compounds from the tannins, alkaloids, organic acids
and flavonoids are thought to be useful for helping improve the condition of
the skin barrier in sufferers with a history of AD because it can act as a
humectant through its effect in increasing acid production. hyaluronic acid in
the skin, as well as an emollient through the phytosterol compound content of
pomegranate seed oil.
A panel
of experts evaluating the use of pomegranate extract in skin care products
found that the concentration of whole red pomegranate extract, which is
commonly used in topical products and has been proven safe and effective, was
0.1%.
The
condition of the skin barrier in AD sufferers appears to be directly
proportional to the activity and severity of the disease, so changes in the
condition of the skin barrier can be used to evaluate the level of success of
therapy (Lee
& Jamil, 2020). The condition of
the skin barrier in AD is known to be closely related to TEWL and pH, where
increasing TEWL will trigger an inflammatory cascade and play a role in causing
a number of clinical abnormalities on the skin surface such as desquamation,
reduced skin elasticity, and epidermal hyperplasia (Del
Rosso & Levin, 2011). while an increase
in pH can cause disruption in the production and composition of skin barrier
lipids, causing damage to the skin barrier and triggering desquamation (Lynde
et al., 2019). Previous research
has proven that a decrease in TEWL and skin pH values is an
accurate indicator for improvement in skin barrier conditions, so that TEWL
examination using a tewameter and skin pH using a pH
meter can be used to assess the success of therapy in AD sufferers (Akdeniz
et al., 2018).
The aim of this study was to prove the
effectiveness of topical administration of 0.1% pomegranate extract (Punica
granatum) in reducing TEWL and skin pH in patients with a history of atopic
dermatitis (AD). Specifically, this study aims to analyze
differences in TEWL and skin pH values before and after topical
administration of 0.1% pomegranate extract and 100% petrolatum, as well as
comparing differences in TEWL and skin pH values between the two
treatments in AD sufferers. The benefits of this research include expanding
knowledge about the benefits of topical pomegranate extract for improving skin
conditions in AD sufferers, providing evidence for clinical practice in the use
of pomegranate extract as a maintenance therapy, additional information for
further research regarding the use of pomegranate extract in topical
formulations, and providing information to the public regarding the benefits of
pomegranate extract in skin care products.
RESEARCH
METHODS
This research will be carried out at the Skin
and Venereology Polyclinic at Demak Regional Hospital, after obtaining ethical
approval until the sample size is met. The research design used a single blind
randomized clinical trial method with a two parallel group pre and post design.
This study included a target population of patients with a history of atopic
dermatitis who were treated at the Skin and Venereology Polyclinic, Demak
Hospital, with samples taken based on inclusion criteria such as age 13-45 years
and willing to take part in the research, as well as exclusion criteria such as
a history of hypersensitivity to pomegranate extract and skin disease other.
The sample will be selected using consecutive sampling, with a total of 60
patients after taking into account the possibility of dropout of 25%. This
study used block randomization for subject allocation, with code A for
pomegranate extract and code B for petrolatum. Evaluation is carried out by
measuring TEWL and skin pH before and after therapy using a tewameter
and pH meter, as well as monitoring compliance through daily record sheets.
Data analysis includes descriptive tests, normality tests, and hypothesis tests
with SPSS version 25. Research ethics involves written consent from the subject
and guarantees confidentiality and compensation of IDR 300,000 per patient.
This research is scheduled to take place from September to May, covering all
stages from preparation, implementation, to data analysis with a total budget
of IDR 36,100,000.
RESEARCH RESULTS AND DISCUSSION
Research result
����������� Recruitment of research
subjects was carried out from August 2023 to April 2024, and in total there
were 34 patients with a history of atopic dermatitis (AD) who met the criteria
to be used as research subjects. There were 34 subjects with a history of AD
who met the inclusion and exclusion criteria and agreed to be included in the
study. Each subject was then randomly allocated to one of 2 research groups,
namely to the treatment group or the control group. A total of 17 subjects were
included in the treatment group which received topical 0.1% pomegranate extract
and 17 subjects were included in the control group which received topical 100%
petrolatum moisturizer, each for 4 weeks. During the follow-up period, no
research subjects dropped out, so all research subjects could be used in the
final analysis.
Characteristics
of Research Subjects
General
characteristics of research subjects in both research groups are shown in table
7.
Table 1. CharacteristicsIn general,
research subjects in the group received 0.1% pomegranate extract and 100%
topical petrolatum.
Characteristics |
Group |
p |
|
Pomegranate
extract 0.1% (n=17) |
Petrolatum
100% |
||
Age
(years) |
30.2�6.04; 31 (20-39) |
29.4�6.43; 28 (19-42) |
0.7� |
Gender |
|
|
|
Man |
5 (29.4%) |
2 (11.8%) |
0.4� |
Woman |
12 (70.6%) |
15 (88.2%) |
|
Education |
|
|
|
SMA/SMK |
4 (23.5%) |
7 (41.2%) |
|
0 (0.0%) |
|
||
S1 |
5 (29.4%) |
|
|
�Unpaired t-test �Fisher-Exact Test |
Overall,
the age of the research subjects ranged from 19 to 42 years (average 29.8�6.16 years), and no significant age differences were
found between the pomegranate extract groups (average 30.2�6.04 years) and petrolatum (mean 29.4�6.43 years). The majority of research subjects appeared
to be female, namely 27 people (79.4%). There were no significant differences
in gender distribution between the pomegranate extract (29.4% men and 70.6%
women) and petrolatum (11.9% men and 88.2% women) groups. However, there are significant
differences in the distribution of education levels between the two research
groups. The pomegranate extract group was dominated by patients with D3
graduates (47.1%), followed by S1 graduates (29.4%) and SMA/SMK (23.5%), while
the petrolatum group was dominated by patients with S1 graduates (58.8%),
followed by SMA/SMK (41.2%) without any D3 graduates.
The
characteristics of research subjects related to AD in the two research groups
are shown in table 8. There were no significant differences found between the
two research groups in terms of duration of suffering from AD, frequency of
bathing, type of bath soap used, habit of bathing in warm water, how to dry the
body, history previous use of moisturizer, initial complaints before receiving
treatment, and treatment history. However, all patients in the group who
received topical 100% petrolatum complained of problems when using the
moisturizer, namely a sticky and oily feeling in 76.5% of patients, and just a
sticky feeling in the remaining 23.5% of patients. In contrast, none of the
patients in the topical 0.1% pomegranate extract group reported any complaints
during use.
Table 2. Characteristics of research subjects
related to AD in the Pomegranate Extract and Petrolatum Moisturizing Group
Characteristics |
Group |
p |
|
Pomegranate
extract 0.1% (n=17) |
Petrolatum
100% (n=17) |
||
Length of suffering from AD (years) |
18.1�4.15; 20.0 (10.0-25.0) |
20.3�6.72; 20.0 (10.0-32.0) |
0.3� |
Bathing Frequency |
|
|
|
1X
a day |
2 (11.8%) |
3 (17.6%) |
1.0 |
2x
a day |
13 (76.5%) |
12 (70.6%) |
|
>
2 x a day |
2 (11.8%) |
2 (11.8%) |
|
Type of Bath Soap |
|
|
|
Antiseptic |
15 (88.2%) |
11 (64.7%) |
0.2 |
Moisturizing
wash |
2 (11.8%) |
6 (35.3%) |
|
Take a warm shower |
|
|
|
Yes |
8 (47.1%) |
5 (29.4%) |
0.3* |
No |
9 (52.9%) |
12 (70.6%) |
|
How to dry the body |
|
|
|
Wiping |
14 (82.4%) |
15 (88.2%) |
1.0 |
Rubbing
vigorously |
3 (17.6%) |
2 (11.8%) |
|
History of Moisturizer Use |
|
|
|
Yes |
12 (70.6%) |
15 (88.2%) |
0.4 |
Seldom |
5 (29.4%) |
2 (11.8%) |
|
Initial Complaint |
|
|
|
Dry |
12 (70.6%) |
11 (64.7%) |
0.7* |
Dry
and Itchy |
5 (29.4%) |
6 (35.3%) |
|
Treatment History |
|
|
|
Topical |
12 (70.6%) |
11 (64.7%) |
0.7* |
Topical
+ oral |
5 (29.4%) |
6 (35.3%) |
|
Usage Complaints |
|
|
|
There
isn't any |
17 (100%) |
0 (0.0%) |
<0.001 |
Sticky |
0 (0.0%) |
4 (23.5%) |
|
Sticky
and oily |
0 (0.0%) |
13 (76.5%) |
|
�Unpaired t-test �Fisher-Exact Test *Testc2 |
In table 2 it can be seen that
the average duration of AD suffering from subjects in the pomegranate extract
group appears to be slightly shorter than the petrolatum group (18.1�4.15 years versus
20.3�6.72 years), although
this difference was not statistically significant (p=0.3).
The frequency of bathing in both
research groups was mostly twice a day, namely in 76.5% of subjects in the
pomegranate extract group and 70.6% in the petrolatum group. The type of bath
soap used in the two research groups also appeared to be similar, namely the
type of soap antiseptics containing chlorhexidine, chloroxylenol, or triclosan (88.2%
in the pomegranate extract group and 64.7% in the Petrolatum group). The
majority of patients in both research groups did not appear to have the habit
of bathing in warm water, namely 52.9% of subjects in the pomegranate extract
group and 70.6% of subjects in the petrolatum group. The method of drying the
body that was most widely used in both research groups was wiping, namely in
82.4% of patients in the pomegranate extract group and 88.2% of subjects in the
petrolatum group.
Most patients have a history of previously used various types of
moisturizing cream, both those with humectant, emollient and occlusive effects,
namely in 70.6% of subjects in the pomegranate extract group and 88.2% of
subjects in the petrolatum group. The initial complaint of research subjects in
both research groups was mostly dry skin, namely in 70.6% of subjects in the
pomegranate extract group and 64.7% of subjects in the petrolatum group. All AD
sufferers who were the subjects of this study reported a history of having
received previous treatment, namely topical treatment only in 70.6% of subjects
in the pomegranate extract group and 64.7% of subjects in the petrolatum group,
while the rest received a combination of topical and oral treatment.
TEWL Value
Before and After Using Extract Moisturizer
Pomegranate and Petrolatum
TEWL
values before and after topical administration of 0.1%
pomegranate extract and topical 100% petrolatum are shown in table 9.
Table
3. TEWL values before and after topical administration of 0.1%
pomegranate extract and 100% petrolatum.
TEWL value |
Group |
p |
|
Petrolatum
100% (n=17) |
|||
Right side |
|
|
|
Baseline |
23.4�5.43; 24.8 (15.7-36.2) |
20.5�7.85; 19.7 (12.2-34.1) |
0.2$ |
4th week |
17.5�4.07; 16.2 (13.1-25.1) |
14.3�4.17; 13.3 (7.8-20.8) |
0.03$ |
p& |
<0.001 |
0.004 |
|
Delta TEWL right side |
-5.9�4.47; -5.1 (-22.6--2.5) |
-6.2�7.32; -4.7 (-21.8-6.8) |
|
Left side |
|
|
|
Baseline |
21.9�4.31; 20.9 (16.7-29.0) |
21.9�8.64; 19.7 (12.2-35.2) |
1.0$ |
4th week |
17.3�5.06; 14.8 (12.5-30.2) |
14.0�3.78; 12.8 (7.6-22.6) |
0.04� |
p& |
<0.001 |
0.002 |
|
Delta TEWL left side |
-4.6�2.36; -5.1 (-7.4-3.5) |
-7.9�8.71; -5.0 (-23.3-6.6) |
0.4� |
TEWL mean value � |
|
|
|
Baseline |
22.6�4.27; 24.0 (16.2-28.8) |
21.2�8.21; 19.7 (12.6-34.5) |
0.5$ |
4th week |
17.4�4.34; 15.2 (12.8-25.4) |
14.1�3.85; 13.6 (7.7-21.7) |
0.03$ |
p& |
<0.001 |
0.003 |
|
Delta TEWL |
-5.2�2.31; -4.8 (-12.8--1.0) |
-7.0�7.95; -5.0 (-21.9-6.7) |
0.9� |
�Right-left side
average �Mann-Whitney test $Unpaired t-test &Baseline vs week 4;
Wilcoxon test |
����������� The
average TEWL value in the pomegranate extract group appeared to have decreased
significantly after 4 weeks (p<0.001), namely from 22.6�4.27 g/m2/hour at the start of the study, to 17.4�4.34 g/m2/hour at the end of the study period (a decrease
of -5.2�2.31 g/m2/hour). The petrolatum group also showed a
significant decrease in the average TEWL value (p=0.003), namely from 21.2�8.21 g/m2/hour at the start of the study, to 14.1�3.85 g/m2/hour at the end of the study period (a decrease
of -7.0�7.95 g/m2/hour).
����������� There
was no difference in the average initial TEWL valueand
final results were significant between the two study groups (p=0.5 and p=0.03),
although the petrolatum group generally showed a lower mean TEWL value than the
pomegranate extract group, both at the start of the study and after 4 weeks.
The petrolatum group also showed a greater reduction in TEWL than the
pomegranate extract group, although this difference was not statistically
significant (p=0.9).
Changes in TEWL values in the volar part of
the right and left arms in both research groups are shown in Figure 1.
C B A
Figure 1. Graph of changes in TEWL values
in the volar part of the right (A) and left (B) arm in the
treatment group (topical 0.1% pomegranate extract) and control (topical 100%
petrolatum), as well as the overall average change in TEWL values (C)
in treatment and control groups.
The graph in Figure 1 shows a
trend of decreasing TEWL values in the treatment and control
groups, both in the volar part of the right arm, left arm, and overall.
The
magnitude of the change in TEWL values (delta TEWL) in the volar
part of the right and left arms and overall, in the two research groups is
shown in Figure 21.
Figure 2. Box-plot
graph of right, left TEWL delta values, as well as the average of right and
left TEWL values.
Figure
2 shows that the median TEWL delta values for the right side,
left side and the mean TEWL values for the right and left sides
in the two study groups are approximately the same. The statistical test
results also showed that the two groups did not show a significant difference
in TEWL delta values (p=0.7 for the right side, p=0.4 for the
left side and p=0.9 for the average of the right and left sides).
pH Value Before and After Using Fruit Extract Moisturizer
Pomegranate and Petrolatum
The
pH values before and after topical administration of 0.1%
pomegranate extract and topical 100% petrolatum are shown in table 10.
Table
4. pH values before and after topical administration of 0.1%
pomegranate extract and 100% petrolatum.
pH value |
Group |
p |
|
Pomegranate
extract 0.1% (n=17) |
Petrolatum
100% (n=17) |
||
Right side |
|
|
|
Baseline |
5.7�0.72; 5,6 (4.8-6.8) |
5.3�0.70; 4.9 (4.4-6.4) |
0.07� |
4th week |
5.7�0.71; 5.7 (4.7-6.8) |
5.4�0.47; 5.3 (4.3-6.1) |
0.4$ |
p& |
<0.001 |
0.5 |
|
Delta pH right |
-0.5�0.07; -0.5 (-0.7--0.4) |
0.1�0.65; 0.1 (-1.3-0.9) |
<0.001� |
Left side |
|
|
|
Baseline |
5.7�0.71; 5.7 (4.7-6.8) |
5.4�0.47; 5.3 (4.3-6.1) |
0.9$ |
4th week |
5.2�0.70; 5.1 (4.2-6.4) |
5.4�0.35; 5.4 (4.5-6.0) |
0.6$ |
p& |
<0.001 |
0.9 |
|
Left pH delta |
-0.5�0.15; -0.5 (-0.8--0.2) |
0.0�0.57; 0.0 (-1.5-0.9) |
0.003$ |
Average pH value� |
|
|
|
Baseline |
5.7�0.71; 5,6 (4.8-6.8) |
5.3�0.57; 5.1 (4.4-6.2) |
0.09$ |
4th week |
5.2�0.71; 5.2 (4.2-6.3) |
5.4�0.31; 5.4 (4.7-5.8) |
0.5$ |
p& |
<0.001 |
0.6 |
|
Delta pH |
-0.5�0.10; -0.5 (-0.6--0.4) |
0.0�0.59; 0.1 (-1.4-0.9) |
<0.001� |
�Right-left side
average �Mann_Whitney test $Unpaired t-test &Baseline vs week 4; Wilcoxon test |
�����������
After 4 weeks, the average pH value in the
pomegranate extract group showed a significant decrease, from 5.7 � 0.71 to 5.2
� 0.71 (decrease of -0.5 � 0.10, p < 0.001), while the petrolatum group
actually experienced an increase in pH from 5.3 � 0.57 to 5.4 � 0.31 (an
increase of 0.0 � 0.59), although this change was not statistically significant
(p = 0.6 ). There was no significant difference
between the average initial and final pH values of the two groups
(p=0.09 and p=0.5), although the petrolatum group showed a lower pH at the
start of the study, while the pomegranate extract group showed a lower pH. lower after 4 weeks. The decrease in pH in the
pomegranate extract group was significantly greater than the petrolatum group
(p<0.001). The graph of changes in pH values in the volar part
of the right and left arms shows a decreasing trend in the pomegranate extract
group, while the petrolatum group shows more varied results. The box-plot graph
also shows that the median delta pH value and average TEWL on both sides of the
arm in the pomegranate extract group were lower than those in the petrolatum
group, with significant differences (p<0.001 for the right side, p=0.003 for
the left side, and p<0.001 for the average of the right and left sides).
Discussion
Patients
with a history of atopic dermatitis (AD) often experience damage to the skin
barrier which is characterized by increased transepidermal
water loss (TEWL) and skin pH. This increase
correlates with the severity of the disease, so TEWL and pH examinations can be
used to evaluate post-therapy skin conditions. This study assessed the effect
of topical administration of 0.1% pomegranate extract for 4 weeks on TEWL and
skin pH in 34 subjects with AD, who were randomly divided into two groups: one
group received pomegranate extract and the other received topical petrolatum.
The two groups have a similar age and gender distribution and characteristics
that are not significantly different, so the comparison data is considered
valid. The majority of subjects showered twice a day and used antiseptic soap
which can damage the skin barrier, while most did not use warm water for
bathing. The method of drying the skin by wiping also has the potential to
affect the skin barrier. Complaints of dry skin are the most common, associated
with deficiencies of natural moisturizing factors and mutations in the
filaggrin gene, which exacerbate damage to the skin barrier. Most patients had
used moisturizers previously, but there was no significant difference in their
use between the therapy and control groups. The use of moisturizers is
recommended as initial and maintenance therapy to improve the condition of the
skin barrier and prevent recurrence. All patients in this study had received
previous therapy, either topical or a combination of topical and oral, with
topical therapy generally used for mild to moderate AD, and combination therapy
only for more severe cases or those that showed no improvement from long-term
topical therapy (Silverberg, 2019).
Effect of Topical 0.1% Pomegranate Extract on TEWL
In this study, the group of patients who
used topical petrolatum showed a significantly lower mean total TEWL value than
the pomegranate extract group after 4 weeks of use (p<0.05). Although
topical 0.1% pomegranate extract also showed a significant reduction in TEWL
with a mean reduction of -5.2�2.31 g/m�/hour (p<0.001), topical
administration of petrolatum resulted in a slightly greater reduction in TEWL,
namely -7.0�7.95 g/m�/hour (p<0.05), although the difference in total TEWL
reduction between the two groups was not significant (p>0.05). This shows
that topical 0.1% pomegranate extract has comparable effectiveness to
petrolatum in reducing TEWL and improving the skin barrier in sufferers of
atopic dermatitis (AD). In addition, the pathogenesis of AD involves dysbiosis
of the skin microbiome, Th2 and Th1 immune reactions, as well as inflammatory
conditions triggered by pro-inflammatory cytokines and reactive oxygen species
(ROS) such as superoxide and hydrogen peroxide. Increased ROS can increase oxidative
stress, modulate pro-inflammatory signaling pathways, and exacerbate damage to
the extracellular lipid matrix at the skin barrier. Pomegranate extract, which
has antioxidant and anti-inflammatory effects, can help improve the condition
of the skin barrier by increasing the skin's water content, improving the skin
microbiome, and reducing TEWL. Polyphenol compounds in pomegranate extract are
known to have a strong antioxidant effect by donating hydrogen atoms to free
radicals, as well as inhibiting lipid peroxidation and cyclooxygenase-2
expression. Previous research shows that pomegranate extract can reduce TEWL
and improve skin condition in animal models and cell cultures. Although
research on topical pomegranate extract for AD is still limited, existing
results support its use as a therapeutic alternative with promising
effectiveness (Cervi et al., 2021).
Effects of
Topical 0.1% Pomegranate Extract onSkin pH
Skin
barrier function is influenced by complex interactions between stratum corneum
pH, filagrin, pH-influenced lipid processing, serine
proteases, and the condition of the skin microbiome, where skin pH plays a role
in regulating the antimicrobial barrier, permeability, and skin barrier
integrity. Changes in pH in the stratum corneum often indicate impaired
epidermal barrier function, with the pH of healthy skin ranging between 4.0�6.0
and the ideal value around 4.5. In this study, the initial pH value in atopic
dermatitis (AD) patients was within the normal range, namely an average of 5.7
� 0.71 in the pomegranate extract group and 5.3 � 0.57 in the petrolatum group,
probably due to history previous use of a moisturizer that improves the initial
skin condition. AD skin may show an increase in pH toward a more neutral state
(>6.5) due to decreased filagrin expression and
active lesions, which is associated with slower recovery and more severe skin
barrier damage. Increased pH can exacerbate skin barrier damage and trigger
desquamation through kallikrein protease activity. In this study, topical
administration of 0.1% pomegranate extract for 4 weeks showed a significant
decrease in pH with an average decrease of -0.5 � 0.10 (p < 0.001), while
the petrolatum group experienced an increase in pH although not significantly
statistics (p<0.05). A better reduction in pH in the pomegranate extract
group probably occurred through improved skin barrier conditions and the
balance of skin microbiota, where commensal bacteria such as Staphylococcus
epidermidis and Bacillus spp. produces fatty acids that help maintain acidic
skin pH and prevent the colonization of pathogenic bacteria.
Difference between
Topical 0.1% Pomegranate Extract and Petrolatum
Petrolatum
is the gold standard moisturizer for the initial therapy of atopic dermatitis
(AD) due to its proven ability to reduce TEWL and repair the skin barrier
effectively through its role as an occlusive agent, with a minimum
concentration of 5% which can reduce TEWL by more than 98%. However, many
patients avoid petrolatum because of its thick, oily consistency, which can
stick to clothing and cause discomfort. In this study, AD sufferers showed
significant discomfort with petrolatum compared with topical 0.1% pomegranate
extract, which caused no complaints during 4 weeks of use. Although topical
administration of 0.1% pomegranate extract and petrolatum showed similar
effectiveness in reducing TEWL without significant differences, petrolatum
showed statistically lower TEWL values at the end of week 4,
possibly due to its greater occlusive effect. In contrast, topical 0.1%
pomegranate extract was more effective in lowering skin pH than petrolatum,
thanks to its additional antioxidant and anti-inflammatory effects as well as
improving the skin microbiome. Topical 0.1% pomegranate extract is also more
comfortable to use and does not cause side effects, so it can be an effective
and safe alternative moisturizer to repair the skin barrier without discomfort,
as well as increasing patient compliance in long-term use. The use of
pomegranate extract in concentrations of 0.1% in skin care products is
generally considered safe and effective, as proven by previous research and
expert panel evaluations.
Research Shortcomings
����������� This
research was carried out by dividing research subjects into 2 groups, each of
which was given different treatment, and does not provide two different types
of therapy on the left and right arms of each patient. This may increase the
risk of variability in the baseline characteristics of patients in the two
study groups and influence the results obtained. In this study, there were no
significant differences in mean initial TEWL or pH values between
the two research groups, although the petrolatum group generally showed a lower
mean initial TEWL value (21.2�8.21 versus 22.6�4.27 g/m2/hour; p=0.5) as well as a lower average initial
pH value (5.3�0.57
versus 5.7�0.71;
p=0.09) when compared to the pomegranate extract group.
CONCLUSION
The conclusion of this study shows that the
TEWL value after topical administration of 0.1% pomegranate extract in patients
with a history of atopic dermatitis (AD) is significantly lower than before
treatment, likewise the TEWL value after topical administration of 100%
petrolatum is also significantly lower. Although the TEWL value after
administering 0.1% pomegranate extract was higher than after administering 100%
petrolatum, the difference was not statistically significant. The skin pH value
after topical administration of 0.1% pomegranate extract was significantly
lower than before treatment, while the skin pH value after topical application
of 100% petrolatum was higher than before treatment although the difference was
not significant. Topical 0.1% pomegranate extract has been shown to be more
effective in lowering skin pH compared to 100% petrolatum, but both have
equivalent effectiveness in reducing TEWL. For future research, it is
recommended that multicenter studies be conducted
with a larger number of subjects to increase statistical power, as well as
compare the effectiveness of two types of moisturizers by applying them to both
arms of one subject for more representative results.
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