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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
Ginger Extract Reduces Oxidative Stress and Improves the Clinical
Outcomes in Patients with Alopecia Areata
Ashwaq Najemaldeen Abbas
Department of Pharmacology, College of Dentistry, University of Sulaimani,
Kurdistan Region, Iraq
DOI: http://dx.doi.org/10.25130/tjops.15.1.03
Abstract
Alopecia areata is a common disorder of known autoimmune
etiology and mostly treated with oral steroids to stimulate new
hair growth with high chances of side effects. The present study
was designed to assess the clinical significance of ginger in
improving oxidative stress and reducing the dose of prednisolone
in patients with alopecia. Forty patients (19 female and 21 male),
with different lesions of stable localized on the scalp were
enrolled in this pilot prospective open-
label clinical study.
Exclusion criteria include the use of any medication th
at may
influence the course of the disease. The patients were allocated
into two groups and treated with 500 mg of ginger powder once
daily for 60 days with either 10 mg or 100 mg/day prednisolone
tablets. Blood samples were obtained at zero time, day-30 and
day-60 and utilized for the evaluation of the erythrocytes contents
of reduced glutathione, and malondialdehyde. The change in body
weight, incidence of acne and the hair loss were also monitored.
The glutathione and malondialdehyde were compared with those
of 20 healthy subjects served as control group. The results
revealed that two-month treatment with ginger improved the rate
of hair growth probably by attenuating free radicals-induced
damage on immune system and addressed the possibility of
reducing
prednisolone dose from 100 mg to 10 mg administered
each other day. In conclusion, the use of ginger may have a role in
protecting radical-
induced damage and decreasing side effects of
high prednisolone dose in patients with alopecia areata.
A r t i c l e i n f o.
Article history:
-Received: 20 /12 / 2019
-Accepted: 31 / 3 / 2020
-Available online:19 / 8 / 2020
Keywords:
Alopecia areata, oxidative
stress, hair loss, prednisolone.
*Corresponding author :
Email
ashwaq.abbas@univsul.edu.iq
Mobile : +964770255889
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E-mail: tjops@tu.edu.iq
Tikrit Journal of Pharmaceutical
Sciences
Journal Homepage: http://tjo-ps.com
009647835274189
009647835274189
۱٦
Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
ﺺﻠﺨﺘﺴﻣ ﻞﯿﺒﺠﻧﺰﻟا ﻞﻠﻘﯾ ﻦﻣ دﺎﮭﺟﻹا يﺪﺴﻛﺄﺘﻟا ﻦﺴﺤﯾو ﺞﺋﺎﺘﻨﻟا ﺔﯾﺮﯾﺮﺴﻟا ﻲﻓ ﻰﺿﺮﻤﻟا ﻦﯾﺬﻟا نﻮﻧﺎﻌﯾ ﻦﻣ ءاد ﺔﺒﻠﻌﺜﻟا
سﺎﺒﻋ ﻦﯾﺪﻟا ﻢﺤﻧ قاﻮﺷا ﺔﺻﻼﺨﻟا
نﻮﻟوﺰﯿﻧﺪﯾﺮﺒﻟا ﻦﻣ ﺔﯿﻟﺎﻋ عﺮﺟ ماﺪﺨﺘﺳﺎﯾ ﺎﺒﻟﺎﻏ ﮫﺟﻼﻋ ﻢﺘﯾو ﺔﻌﺋﺎﺸﻟا ﺔﯿﺗاﺬﻟا ﺔﻋﺎﻨﻤﻟا ضاﺮﻣأ ﻦﻣ ﺔﺒﻠﻌﺜﻟا ءاد ﺮﺒﺘﻌﯾ يﺬﻟا
ﻌﻣ ﻦﯿﯿﺴﺤﺗ ﻲﻓ ﻞﯿﺒﺠﻧﺰﻟا ﺔﯿﻟﺎﻌﻓ ﻢﯿﯿﻘﺘﻟ ﺔﺳارﺪﻟا هﺬھ ﻢﯿﻤﺼﺗ ﻢﺗ .ﺔﯿﺒﻧﺎﺠﻟا ضاﺮﻋﻷا ﺮطﺎﺨﻣ ﻲﻓ ةدﺎﯾز ﻊﻣ ﻖﻓاﺮﺘﯾﺎ طﺮﻓ ﺮﯿﯾ
مﺪﺨﺘﺴﻤﻟا نﻮﻟوﺰﯿﻧﺪﯾﺮﺒﻟا ﺔﻋﺮﺟ ﻞﯿﻠﻘﺗو ةﺪﺴﻛﻷا رﺎﯿﺘﺧا ﻢﺗ .ضﺮﻤﻟا جﻼﻌﻟ٤۰ ) ﺎﻀﯾﺮﻣ۱۹ و ثﺎﻧا۲۱ ﻦﻣ (رﻮﻛذ
ﺼﻤﻟاﺎﺬھ ﻲﻓ ﺔﻛرﺎﺸﻤﻠﻟ ﺮﻘﺘﺴﻤﻟا ﺔﺒﻠﻌﺜﻟا ءاﺪﺑ ﻦﯿﺑ ﻢﮭﺟﻼﻋ ﻢﺗو ﻦﯿﺘﻋﻮﻤﺠﻣ ﻰﻟا ﻰﺿﺮﻤﻟا ﻢﯿﺴﻘﺗ ﻢﺗ .ﺔﯾﺮﯾﺮﺴﻟا ﺔﺳارﺪﻟا ه
ﺎھراﺪﻘﻣ ﺔﻋﺮﺠﺑ٥۰۰ ةﺪﻤﻟ ﻞﯿﺒﺠﻧﺰﻟا ةدﺎﻣ ﻦﻣ مﻮﯾ/ﻢﻐﻠﻣ٦۰ ﻰﻟا ﺔﻓﺎﺿأ مﻮﯾ۱۰ وأ مﻮﯾ/ﻢﻐﻠﻣ۱۰۰ ةدﺎﻣ ﻦﻣ ﻢﻐﻠﻣ مﻮﯾ/
ﺪﻌﺑو جﻼﻌﻟﺎﺑ ءﺪﺒﻟا ﻞﺒﻗ مﺪﻟا ﻦﻣ تﺎﻨﯿﻋ ﺬﺧأ ﻢﺗ .ﻢﻔﻟا ﻖﯾﺮط ﻦﻋ نﻮﻟوﺰﯿﻧﺪﯾﺮﺒﻟا۳۰ و٦۰ ﻟاﻮﺘﻟا ﻰﻠﻋ مﻮﯾ ﺖﻣﺪﺨﺘﺳاو ،ﻲ
ﻲﻓ ةدﺎﯾﺰﻟاو سأﺮﻟا ﻲﻓ ﺮﻌﺸﻟا ﻮﻤﻧ ﻲﻓ ﺮﯿﻐﺘﻟا ىﻮﺘﺴﻣ سﺎﯿﻗ ﻰﻟا ﺔﻓﺎﺿﻷﺎﺑ ،ﺪﯿھﺪﻟﺎﯾاﺪﻧﻮﻟﺎﻤﻟا و نﻮﯿﺛﺎﺗﻮﻠﻜﻟا ىﻮﺘﺴﻣ سﺎﯿﻘﻟ
ﺪﻌﺑ ﮫﻧأ ﺞﺋﺎﺘﻨﻟا تﺮﮭظأ .بﺎﺒﺸﻟا ﺐﺣ رﻮﮭظ ﻰﻟا ﺔﻓﺎﺿا ﻢﺴﺠﻟا نزو٦۰ ىﻮﺘﺴﻣ ﺾﻔﺨﻧا ﻞﯿﺒﺠﻧﺰﻟا ماﺪﺨﺘﺳا ﻦﻣ مﻮﯾ
ﯿﺛﺎﺗﻮﻠﻜﻟا ىﻮﺘﺴﻣ ﻊﻔﺗراو ﺪﯿھﺪﻟﺎﯾﺪﻧﻮﻟﺎﻤﻟا ﻰﻟا ﺔﻓﺎﺿا ءاﺮﻤﺤﻟا تﺎﯾﺮﻜﻟا ﻲﻓ نﻮلﺎﻤﺘﺣا ﻦﻣ نﻮﻟوﺰﯿﻧﺪﯾﺮﺒﻟا ﺔﻋﺮﺟ ﺾﻔﺧ
۱۰۰ ﻰﻟا ﻢﻐﻠﻣ۱۰ ﻦﻜﻤﯾ .بﺎﺒﺸﻟا ﺐﺣ رﻮﮭظ ﻦﻣ ﺪﺤﻟاو ﺮﻌﺸﻟا ﻮﻤﻧ ﻲﻓ سﻮﻤﻠﻣ ﻦﺴﺤﺗ ﻰﻟا جﻼﻌﻟا ىدأ ﺎﻤﻛ .ﻢﻐﻠﻣ
ﻞﯿﺒﺠﻧﺰﻟا ماﺪﺨﺘﺳا نﺄﺑ جﺎﺘﻨﺘﺳﻷاﺪﻗ و ضﺮﻤﻟا ﻦﻋ ﺔﺠﺗﺎﻨﻟا ةﺪﺴﻛﻷا طﺮﻓ ﺮﯿﺛﺄﺗ ﻦﻣ ﺔﯾﺎﻤﺤﻟا ﻲﻓ رود ﮫﻟ نﻮﻜﯾ ﻦﻣ ﺪﺤﻟا ﻚﻟﺬﻛ
ﺔﺒﻠﻌﺜﻟا ءاد جﻼﻋ ءﺎﻨﺛا نﻮﻟوﺰﯿﻧﺪﯾﺮﺒﻟا ﻦﻣ ﺔﯿﻟﺎﻋ عﺮﺟ ماﺪﺨﺘﺳا ﻦﻋ ﺔﺠﺗﺎﻨﻟا ﺔﯿﺒﻧﺎﺠﻟا ضاﺮﻋﻷا ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ
Introduction
Alopecia areata (AA) is a common,
unpredictable, non-scarring form of hair
loss(1-4). This disorder affects all age
groups with a higher prevalence in
children and adolescents(4). Although the
causes are not well caracterized, its
etiology is mostly associated with an
alteration in the immunological responses
of the biological system(5,6). Although
many pharmacological approaches are
utilized for the management of AA, the
current treatments are not directly
targeting the etiology of the disorder but
rather the resulting inflammatory
consequences and the growth inhibitory
factors produced by this response(5,6).
Moreover, the use of many effective
agents in this regard may be associated
with seriouse adverse effects that limit
continuous and chronic use of these
agents(7). In this regard, the use of high
systemic doses of corticosteroids (e.g.,
prednisolone) alone or in combination
with topical agents(8-10) is associated with
serious adverse effects including
metabolic dysregulation, hypertension
and weight gain(11,12). Meanwhile, the use
of natural supplements with powerfull
antioxidant properties for treatment of
many chronic disorders including AA
was considered as a common practice;
this may be attributed to the sinificant
ameloration of the oxidative stress state
accompanied with AA pathogenesis and
improvement of the antioxidant capacity
of the affected patient; this can influence
the disease severity and improves
treatment outcomes(13). Although many
natural agents including quercetin,
Houttuynia cordata, Perilla frutescens
and green tea are tried in experimental
models of AA and clinical setting with
inadequate evidence, some of the results
seem to be promising(14-16). The ginger
extract (Zingiber officinale (L.) Rosc) is a
well known product and widely used for
its pleiotropic properties that includes
antioxidant, anti-inflammatory,
hypoglycemic, anticancer and
antibacterial activities(17-20). The present
study was designed to evaluate the role of
ginger extract in the amelioration of
oxidative stress in patients with alopecia
areata and the possibility of reducing the
dose of prednisolone during treatment.
Patients and Methods
Participants
Enrollment of AA patients, intervention
and the analysis of outcomes were
performed during January-November
2017 in a private dermatology clinic, Al-
Rusafa, Baghdad. For consistency, the
AA diagnosis was performed by a
consultant dermatologist according to the
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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
National Alopecia Areata Foundation
guidelines(18). In the present study, a total
of 62 AA patients were screened for
eligibility and only 40 patients met the
inclusion criteria (19 females, 21 males).
Twenty healthy subjects (8 females, 12
males) age- and sex-matched with the AA
patients were enrolled in the present
study and served as a control group. As
inclusion criterea, the average age of the
patients ranged from 17 to 45 years; in
addition, all the included AA patients
have no other chronic illnesses or a
history of chronic drug use. The severity
of AA was assessed by combination of
hair loss and hair density. According to
the Severity of Alopecia Tool (SALT)
scores, the cases are ranked into 5
categories that represent subgrouping of
percent scalp hair loss, as S1, S2, S3, S4
and S5. All the AA patients had not
treated previously with any systemic
therapy such as corticosteroids,
minoxidil, or anthralin within the last two
months. They also were not exposed to a
topical therapy that affects cellular
immunity or photo chemotherapy.
Study Design
The eligible AA patients were invited to
participate in this prospective open-label
clinical study. Firstly, all participants
were addressed about the study protocol
by providing a full description of the
objectives, benefits and the expected
adverse events of the administered
treatment during the study. This open-
label pilot clinical study was approved by
the local ethical committee of the College
of Medicine, University of Sulaimani
(CS-1/9-2018). All participants were
asked to sign informed consent before
enrollment in the study. At the first visit,
baseline data were obtained from the
participants, and the AA patients were
allocated into two groups using simple
randomization method based of 1:1 ratio;
the 1st group (20 patients) was treated
with 100 mg/day prednisolone tablets
while the other 20 patients received 10
mg/day prednisolone tablets (2nd group);
both groups concomitantly administered
a single capsule/day containing 500 mg
of a standard ginger powder (Green
Plants of Life Pharmaceutics Co., Iran)
one hour after the breakfast for 60 days.
The ginger capsules were provided to the
patients in monthly bases to insure
compliance with the treatment protocol.
The AA patients were advised to follow a
modified diet and physical activity plan,
and avoid consumption of any dietary
supplements and other treatments that
may interfere with the study outcome. To
ensure compliance of the participants
about ginger capsules consumption,
phone calls were made at the end of each
30 days. For comparison of the
biochemical data, 20 healthy subjects age
matched with patients were selected as a
control group (3rd group).
Outcomes measurement
Clinical outcome
The response rate to the treatment was
followed by measurment of the size of
alopecic area, in addition to the side
effects of the systemic steroid through
monitoring the increase in body weight
and appearance of signs of acne. The
effects of of ginger extract when used
with either 10 mg or 100 mg
prednisolone were evaluated on hair
growth using the pull test. The pull test
enables the evaluation of diffuse scalp
hair loss. Gentle traction was exerted on a
bunch of hairs (about 60) in three areas of
the scalp (frontal, temporal, and occipital)
and the number of extracted hairs was
counted(21). The dermatologist takes a few
strands between the thumb and forefinger
and pulls them gently.
Blood sampling and analysis of
markers
Venous blood samples (10 ml) were
obtained from the AA patients at zero
time, day-30 and after 60 days following
an overnight fasting, kept in heparinized
tube on ice at 4°C. The blood was
centrifuged for 30 minutes at 400 x g and
20°C to obtain the erythrocytes fraction
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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
utilizing a standard procedure(22). Only
single blood sample was obtained from
subject in the control group and utilized
for comparison. Using standard methods,
the isolated erythrocytes were utilized for
the assessment of reduced glutathione
(GSH)(23) and malondialdehyde
(MDA)(24). The hemoglobin content of
the erythrocytes was measured using
Beckman AU5800 automatic blood
analyzer (Beckman Coulter, Brea, CA,
USA).
Statistical analysis
Data was analyzed using GrapPad prism
software 5.1 (GraphPad Software Inc., La
Jolla, CA, USA). The results were
expressed as numbers and percentages or
means±SD. Nonparametric continuous
variables were compared with the Mann-
Whitney U test. The parametric variables
were compared using paired t-test for to
compare the same mean in two occations
and unpaired t-test to compare means of
different groups. P values < 0.05 were
considered as statistically significant.
Results
Table 1 showed the characteristic features
of the AA patients enrolled in the study.
Table 2 showed that the MDA content of
the erythocytes in AA patients was
significantly elevated in both treatment
groups (before treatment) compared with
that reported in healthy control group.
The combination of ginger extract
(500mg/day) with either 10 mg or 100
mg of prednisolone decreases
significantly the erythocyte MDA
concentration after 30 days compared
with the baseline value and this
significant reduction of the MDA content
was continued after 60 days of treatment
and found to be comparable in both
groups. In Table 3, the already reduced
glutathione (GSH) content of the
erythocytes in AA patients before
treatment was significantly decreased in
both treatment groups compared with that
reported in healthy control group. The
combination of ginger extract
(500mg/day) with either 10 mg or 100
mg of prednisolone increases
significantly the erythocytes GSH
concentrations after 30 days compared
with the baseline value; this significant
elevation of the erythrocytes GSH
content was continued after 60 days of
treatment and found to be similar in both
groups. Table 4 demonstrates the
influence of using different doses of
prednisolone with ginger extract on the
body weight of the AA patients. This
treatment approach produces significant
increase in the body weigh after 30 and
60 days of treatment and their values are
comparable in both groups throughout the
entire period of treatment. In table 5, the
severity of acne formation (the side effect
of using corticosteroids) was found to be
lower in the group treated with the lower
dose of prednisolone (10 mg/day)
compared with the higher dose.Regarding
the influence of using ginger on the
clinical features of hair loss,Figure 1
showed that there is no significant
difference (P=0.19) between the two
treatment groups regarding the percent
reduction in hair pull test after 30 days of
treatment. However, at day-60 the
percent reduction in hair pull test of the
group treated with 10 mg prednisolone +
500 mg ginger was significantly higher
than that of the group treated with 100
mg prednisolone + 500 mg ginger
(P<0.001).
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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
Table (1):- The demographic and base-line characteristics of patients with alopecia
areata
Parameter
Mean.
SD
Age mean±SD (Year)
25.7
8.0
Disease duration mean±SD (Year)
6.2
1.2
Gender
No.
%
Male
21
52.5
Female
19
47.5
SALT* score
S1
14
35.0
S2
12
30.0
S3
6
15.0
S4
6
15.0
S5
2
5.0
Total
40
100.0
*SALT: Severity of Alopecia Tool
Table (2):- Effect of the using 500 mg ginger extract with prednisolone tablets (10 or
100 mg/day) on the erythrocytes MDA contents in patients with alopecia areata.
Treatment group
Erythrocyte MDA (nmol/g Hb)
Pre-treatment
Day-30
Day-60
Healthy subjects (n=20)
0.04±0.008
-
-
10 mg prednisolone+Ginger exract (n=20)
0.91±0.05*a
0.32±.02b
0.12±.01c
100 mg prednisolon+Ginger extarct (n=20)
0.92±0.04*a
0.32±0.01b
0.13±0.02c
Values are presented as mean±SD; n:
number of subjects;* significantly
different compared with the healthy
subjects(t-test for two indendent
samples); values with non-identical
superscripts (a,b,c) within the same
treatment group are significantly different
(paired t-test; P<0.05).
Table (3):- Effect of the using 500 mg ginger extract with prednisolone tablets (10 or
100 mg/day) on the erythrocytes GSH contents in patients with alopecia areata
Treatment group
Erythrocyte GSH (μmol/g Hb)
Pre-
treatment
Day-30 Day-60
Control (n=20)
23.2±3.7
-
-
10 mg prednisolone+Ginger exract (n=20)
8.3±0.51*a
13.0±0.42b
19.3±0.74c
100 mg prednisolon+Ginger extarct (n=20)
8.1±0.73*a
12.8±0.47b
18.9±0.76c
Values are presented as mean±SD; n:
number of subjects;* significantly
different compared with the healthy
subjects(unpaired t-test); values with non-
identical superscripts (a,b,c) within the
same treatment group are significantly
different (paired t-test; P<0.05).
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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
Table (4):- Effect of the using 500 mg ginger extract with prednisolone tablets (10 or
100 mg/day) on the changes in body weight of patients with alopecia areata
Treatment group
Body weight (Kg)
Pre-treatment
Day-30
Day-60
10 mg prednisolone+Ginger exract (n=20)
69.6±8.6a
71.3±8.5*b
72.4±8.5*c
100 mg prednisolon+Ginger extarct (n=20)
67.2±5.3a
70.3±5.2*b
77.1±4.7*c
Values are presented as mean±SD; n:
number of subjects;* significantly
different compared with pre-treatment
values(unpaired t-test); values with non-
identical superscripts (a,b,c) within the
same treatment group are significantly
different (paired t-test; P<0.05).
Table (5):- Effect of the using 500 mg ginger extract with prednisolone tablets (10 or
100 mg/day) on the severity of acne formation in patients with alopecia areata
Treatment group
Presence of Acne
Pre-treatment
Day-30
Day-60
10 mg prednisolone+Ginger exract (n=20)
negative
+
+
100 mg prednisolon+Ginger extarct (n=20)
negative
++
+++
Figure (1): Reduction in hair pull test
score from baseline for the use of 500 mg
ginger ginger extract with 100mg or
10mg prednisolone. n=20 patients in each
group.
Discussion
Corticosteroids are part of the treatment
in many disorders in which the
inflammation is thought to be caused by
excessive or inappropriate activation of
the immune system like in Alopecia
areata(21,25-28). When administered in high
doses, corticosteroids can reduce the
severity of inflammation by blocking the
action of prostaglandins responsible for
triggering the inflammatory response(29).
They also temporarily depress the
immune system by reducing the activity
of certain types of white blood cells. In
the present study, the AA patients
showed elevated oxidative stress state
compared with healthy controls, and the
use of ginger with different doses of
prednisolone improves this condition in
both groups. The extent of hair loss and
the age of the patient are the bases
utilized to select an appropriate treatment
for patients with alopecia areata(3). For
those with more than 50% scalp hair loss
one may consider the use of systemic
corticosteroids but the concern about
long-term use and the side effects of
systemic corticosteroids must be taken
into consideration(30). The present study
revealed the presence of endogenous
oxidative stress in both groups of
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Tikrit Journal of Pharmaceutical Sciences 15(1) 2020 ISSN: 1815-2716
patients, as manifested by the increased
MDA levels and decreased GSH contents
in the erythrocytes. This oxidative stress
may result from the activated phagocytes
that generated excessively many free
radicals and and predispose to lipid
peroxidation(31). Data of the present study
also indicated that, despite the difference
in oral prednisolone dose (10 vs. 100 mg)
between the two groups, coadministration
of a supplement with powerful
antioxidant properties with prednisolone
therapy resulted in comparable and
significant decrease in MDA levels and
correction of the GSH content in blood,
as well as similar improvement in the rate
of hair growth with less side effect (acne
and weight gain) regardless of the dose of
prednisolone. Previous study in our lab
showed that, without antioxidant therapy,
the effect of 100 mg prednisolone was
more prevalent than the lower doses of
prednisolone in improving hair growth in
alopecic patients(13). Therefore, the
addition of supplement like ginger extract
with powerful antioxidant properties,
mostly attributed to its polyphenols and
flavonoids content, to the corticosteroids
attenuated the negative effects of
oxidative stress on the immune system
and decreased the need for higher doses
of the systemic steroid; thereby decreased
the unwanted side effects associated with
the prolonged use of high doses. The
present data represent the outcome of a
pilot trial; hence many limitation may not
enable a significant clinical conclusion
including small sample size, duration of
treatment and the use of ginger extract as
add-on option with other treatment
protocols. However, the presented data
may be useful to initiate larger multi-
center and placebo-controlled study.
Conclusion
The addition of supplement like ginger
extract with powerful antioxidant
properties to the corticosteroids
attenuates the alopecia areata-associated
oxidative stress and may decrease the
need for higher doses of the systemic
steroid during treatment of alopecia
areata; thereby, decreased the unwanted
side effects associated with the prolonged
use of the high doses.
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