Received: 03/10/2024 Accepted: 25/01/2025 Published: 06/03/2025 1 of 8
https://doi.org/10.52973/rcfcv-e35566 RevistaCientíca,FCV-LUZ/Vol.XXXV
ABSTRACT
This study explored the effects of comfrey (Symphytum ofcinale)
on treating third–degree burns in a rat model, demonstrating
promising results. A hot iron created standardized burns,
after which three groups of rats received different treatments:
no treatment (control), vaseline, or a 20% comfrey ointment.
Histopathological assessments at the 7 days and 14 days marks
showed accelerated healing in the comfrey–treated group
compared to the control, indicating comfrey’s potential for
enhancing wound recovery. Additionally, comfrey’s antioxidant
capacity was evaluated using assays such as Fe³
+
and Cu²
+
reducing
power and free radical scavenging activities (DPPH· and ABTS•
+
assays). The IC50 values for DPPH· scavenging were 69.30 µg·mL
-1
(water extract) and 46.20µg·mL
-1
, while for ABTS•
+
scavenging they
were 77.00 µg·mL
-1
and 69.30 µg·mL
-1
(ethanol extract). These
results conrm that comfrey exhibits signicant antioxidant activity,
likely contributing to its wound–healing properties. Overall, this
study suggests comfrey as a safe traditional treatment option for
burn healing, with its benets likely stemming from its antioxidant
activity. The results indicate this combination is a safe traditional
medicine for clinical applications at proper doses.
Key words: Comfrey (Symphytum ofcinale); antioxidant activity;
wound healing
RESUMEN
Este estudio exploró los efectos de la consuelda (Symphytum
ofcinale) en el tratamiento de quemaduras de tercer grado en
un modelo de ratas, demostrando resultados prometedores.
Se crearon quemaduras estandarizadas con un hierro caliente,
después de lo cual tres grupos de ratas recibieron diferentes
tratamientos: sin tratamiento (control), vaselina o una pomada con
un 20% de consuelda. Las evaluaciones histopatológicas tanto a los
7 como a los 14 días mostraron una curación acelerada en el grupo
tratado con consuelda en comparación con el grupo control, lo que
indica el potencial de la consuelda para mejorar la recuperación
de las heridas. Además, se evaluó la capacidad antioxidante de
la consuelda utilizando ensayos como el poder reductor de Fe³
+
y
Cu²
+
y las actividades de scavenging de radicales libres (ensayos
DPPH· y ABTS•
+
). Los valores de IC50 para la eliminación de
DPPH· fueron 69,30 µg·mL
-1
(extracto acuoso) y 46,20 µg·mL
-1
,
mientras que para la eliminación de ABTS•
+
fueron 77,00 µg·mL
-1
y 69,30µg·mL
-1
(extracto etanólico). Estos resultados conrman
que la consuelda exhibe una actividad antioxidante signicativa, lo
que probablemente contribuye a sus propiedades de cicatrización
de heridas. En general, este estudio sugiere la consuelda como
una opción segura de tratamiento tradicional para la curación
de quemaduras, con benecios que probablemente provienen
de su actividad antioxidante. Los resultados sugieren que esta
combinación es una medicina tradicional segura para aplicaciones
clínicas en dosis adecuadas.
Palabras clave: Consuelda (Symphytum ofcinale); actividad
antioxidante; cicatrización de heridas
Antioxidant and wound healing effects of comfrey (Symphytum ofcinale)
Efectos antioxidantes y de cicatrización de heridas de la consuelda (Symphytum ofcinale)
Selvinaz Yakan
1
* ,Yusuf Kenan Dağlıoğlu
2
, Kıvılcım Eren Erdoğan
3
, Rüya Sağlamtaş
4
, İlhami Gülçin
5
1
Ağrı İbrahim Çeçen University, Eleşkirt Celal Oruç School of Animal Production, Animal Health Department. Ağrı, Türkiye.
2
Kirşehir Ahi Evran University, Faculty of Medicine, Department of Microbiology. Kırşehir, Türkiye.
3
Çukurova University, Faculty of Medicine, Department of Pathology. Adana, Türkiye.
4
Ağrı İbrahim Çeçen University, Vocational School of Health Services. Ağrı, Türkiye.
5
Atatürk University, Faculty of Science, Department of Biochemistry. Erzurum, Türkiye.
*Corresponding author: syakan@gmail.com
Antioxidant and wound healing eects of comfrey / Yakan et al.______________________________________________________________________
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INTRODUCTION
Since ancient times, medicinal plants have been utilized to
enhance human health and extend lifespan in various parts of
the world. These plants are commonly used by millions, not only in
areas with limited access to modern healthcare but also by urban
populations in both developing and developed nations [1]. Türkiye
is home to a diverse flora, with around 11,000 species. The local
population utilizes this abundant plant life for various purposes [2].
It is well known that medicinal plants have antioxidant properties
[3, 4] and may have greater potential for treating multiple biological
disorders [5, 6, 7].
Comfrey (Symphytum ofcinale) is a medicine plant thought to
be effective against wound site infection. The European Medicines
Agency approves the use of comfrey on the skin. It was used as
a reducing agent for the cytotoxic effects of antimicrobial active
ingredients in the formula. It is also used for myogenic pain and
arthralgia. Also, the therapeutic properties of comfrey, which are
based on its anti–inflammatory and analgesic effects, stimulate
granulation and support tissue regeneration. Thanks to those
properties, it is used for wound treatment in folk medicine [8, 9].
Asimgil [9] reported that this medicinal plant was used to treat
breast cracks and burn wounds.
Tissue damage caused by thermal, electrical, and radioactive
agents is a burn. Burns range from some that can be treated and
followed on an ambulatory basis to some that cause multi–organ
failure. Burns cause some difculties for individuals and societies
because of mortality and morbidity [10]. Nearly 11 million people
worldwide undergo medical treatment, and every year almost
300.000 people die because of burns [11]. Mortality rates due to
burn wounds decrease in parallel with improvements in patient
care and treatment [12]. Regardless of the etiology of burns, the
tissue damage by burns is characterized by the denaturation of
cell proteins, which becomes more severe depending on the cause
and degree of injury [10]. A wound is divided into three degrees
that depend on the depth of the wound; the manner of treatment
is planned according to this degree: First–degree burns affect only
the epidermis. Burns that affect the entire epidermis and supercial
dermis are classied as second–degree burns. Third–degree burns,
which extend through the epidermis and dermis, are full–thickness
burns [13]. The aim of the treatment of burn wounds is quick re–
epithelialization. It is required that the local agents used during the
treatment of burn injury should be hygroscopic and easily applicable
to speed up the quick re–epithelialization and prevent the possible
wound infection [12], and dehydration of the wound [14].
Antimicrobial agents are routinely used to treat chronic and
problematic wounds [14, 15, 16]. Comfrey was chosen for this
study because of the above–mentioned characteristics. This
study aims to reveal comfrey’s antioxidant effects and evaluate
its wound–healing effect according to ethnobotanical records.
MATERIALS AND METHODS
Plant materials
Comfrey was collected from Selçuk, İzmir province Türkiye
(Latitude: 100 m) at the date of 08/24/2018. Whole plant parts
were used for extractions. This plant and identied by Volkan
Eroğlu, Ege University, Faculty of Sciences and Department of
Biology, İzmir, Türkiye. The plant materials were authenticated by
Herbarium Universitatis Aegaeensis Izmir (Herbarium No: 42708).
Preparation of plant extract
A 100 g flowery comfrey plant, dried in the shade without direct
exposure to sunlight and ground in a blender (Arzum AR-1111,
Türkiye), was macerated in 80% ethanol (2×300 mL) for 2 days (d),
with constant stirring at room temperature (between 21-27°C). The
extracts were separated from the plant material by ltering twice
through lter paper for increased efciency. The ltered extracts
were stored in glass flasks until further use. Following this, the
ethanol extract was evaporated to dryness under reduced pressure
using a rotary evaporator (Buch, R-210, Canada), resulting in a yield
of 38.7 g. The dried extracts were then stored at -80°C (Arçelik,
A++, Türkiye) until used in experiments. A 20% concentration of
the dried extracts was applied to the burn wounds of rats (Rattus
norvegicus) in the treatment group.
Antioxidant activities
The total phenolic compounds in the Comfrey extracts were
determined with Folin–Ciocalteu reagent according to the method
of Slinkard and Singleton [17] using gallic acid as a standard
phenolic compound. For determination of Fe
3+
reducing ability of
comfrey, Fe
3+
(CN
–
)
6
to Fe
2+
(CN
–
)
6
reduction method was used. The
spectrophotometer (Shimadzu UV-1800, Japan) was measured
at 700 nm [18]. Cu
2+
reducing power was used as a second
reducing ability method for comfrey. Cu
2+
reducing capability
was performed according to the CUPRAC method [19] using the
ethanolic neocuproine solution.
The absorbance of samples was recorded with a
spectrophotometer (Shimadzu UV-1800, Japan) at 450 nm after
30 min [20]. DPPH radical scavenging activity of comfrey was
performed according to the method of Blois [21] as described
previously in detail [4]. The absorbance values of samples were
recorded at 517 nm in a spectrophotometer (Shimadzu UV-1800,
Japan) [22]. ABTS radical scavenging activity of comfrey was
performed using the spectroscopic (Shimadzu UV-1800, Japan)
method described by Huyut et al. [23]. The ABTS radical cation
(ABTS•
+
) was acquired by reacting a 7.0 mM solution of ABTS
with 2.45 mM K
2
S
2
O
8
. The extent of decolorization is calculated
as a % reduction of absorbance [24]. The percentage of metal
chelating and radicals scavenging was computed using the
following equation: SE (%) = [1×(As/Ac)]×100. Here, SE is radical
scavenging effects, Ac is the absorbance value of control and As
is the absorbance value of comfrey [25].
Experimental animals
In this study, 42 female Wistar–Albino rats (180-200 g) (Mettler
Toledo, XPR205, Switzerland) provided by the animal breeding
laboratories of Çukurova University Experimental Application and
Research Center are used. During the experiment, the animals
were allowed food and water ad libitum (standard rat feed pellets
supplied by the Forage Foundation). The animals were kept
at constant room temperature (22°C) and they were fed. The
Institutional Animal Ethical Committee of Çukurova University
approved this study (Protocol no: 2017/6).
Antioxidant and wound healing eects of comfrey / Yakan et al.______________________________________________________________________
_________________________________________________________________________________________________Revista Cientica, FCV-LUZ / Vol.XXXV
3 of 8
Wounds
For general anesthesia, 10 mg·kg
-1
of Xylazine hydrochloride
(Alfazyne®, 2%, Alfasan International, 3440 AB, Woerden, Holland)
and 50 mg·kg
-1
of Ketamine (Ketalar®, Pfizer Pharma GMBH,
Germany) were administered. Following anesthesia, the large areas
on all rats’ dorsal that the last rib joins with the thoracic vertebra
and 1-2 lumbar vertebra’s spinous process placed in there, and it
comprises the vertebra posterior were shaved completely. The dorsal
of rats was cleaned with povidone–iodine. A 50 g iron block of 15
mm diameter is used for the infliction of burns. The iron block was
preheated for approximately 10 min until it reached a temperature of
70–100°C, and then it was applied without any additional pressure
except the self–gravity of the block. The block was applied straightly
for 10 seconds and a third–degree burn was created (full–thickness
burns). The same procedure was repeated for each of the rats.
Treatment protocol
Animals are randomly divided into three groups and treatment
started 24 hours (h) after the burning procedure. Group 1 (control;
n: 14): this group is not subjected to any kind of treatment. Group2
(n: 14): vaseline only to observe the placebo effect of the vehicle;
group 3 (n: 14) 20% (2 g extract + 8 g vaseline) comfrey ointment. A
thin layer of ointment that covered the wound surface was applied
once each d. Carprofen was given at 5 mg·kg
-1
to the wound area
of all rats for analgesia once daily during the experiment.
Measuring healing of burns
Diameters of burn wounds were recorded by measuring the
length in mm with the help of a digital caliper (Mitutoyo 500-196-
30, Japan) on the 1
st
, 7
th
, and 14
th
d after the burn injury. Measuring
was carried out based on the borders of tissue that complete the
re–epithelialization during the healing process. The diameter of
the burn was recorded as 15 mm in all groups on the rst d of
measurement. During the 7
th
and 14
th
d, macroscopic ndings
related to healing burns were recorded. Any chemicals to remove
accumulated drug residues on the burn wound area were not used.
From the d the wound was formed, all the lesions were followed
up continuously to the healing. Measurement of the wound area in
the wound lines was photographed before applying the materials
used on the wound during dressing changes in each group and
recorded on the scale created by measuring the length.
Histopathological evaluation
In this research, in all three groups, 7 rats were euthanized on the
7
th
d of the experiment, and on the 14
th
d of the experiment, the rest
of the rats in the group were euthanized by high–dose anesthesia.
Full–thickness tissue samples (15×15 mm), which included the
whole burned sites, were harvested immediately after euthanasia
each rat. After the collected tissue samples were xed in 10%
formaldehyde solution for the histopathological examination,
parafn blocks were prepared and samples that were 5 micron–
thick were taken from them. These sections were then stained
with Hematoxylin–Eosin (H&E) and histological ndings related
to ulcer, inflammation, epithelization, granulation tissue, and
angiogenesis were evaluated under the light microscope (Olympus,
BX53, Japan). Grading of histopathological parameters was done
as in the literature [26].
Statistical analysis
Statistical analysis was made through one–way analysis of
variance (ANOVA) with multiple comparison tests (Tukey HSD).
P value less than 0.05 was accepted as the level of statistical
signicance. The values were presented as mean ± standard error
of the mean (SEM).
RESULTS AND DISCUSSIONS
Antioxidant results
In the present study, the antioxidant and antiradical potentials of
comfrey were evaluated spectrophotometrically using a Shimadzu
UV-1800 (Japan) and various bioanalytical methods, including Fe³
+
–
reducing antioxidant assay, cupric ion (Cu²
+
)–reducing (CUPRAC)
assay, DPPH• scavenging activity, and ABTS•+ scavenging activity.
The results of comfrey’s antioxidant activity are presented in TABLE
I. The Fe[(CN)
6
]
3-
to Fe[(CN)
6
]
2-
reduction method was employed
for the rst time to assess the antioxidant capacity of comfrey
[3]. As shown in TABLE I, comfrey extracts at a concentration of
10 µg·mL
-1
demonstrated signicant Fe[(CN)
6
]
3-
reducing activity,
with these differences being statistically signicant (P<0.01). An
increase in the absorbance of Fe[(CN)
6
]
2-
in the reaction mixture
indicates enhanced reducing power, corresponding to higher
complex formation. The reducing ability followed this order:
Trolox (1.807 ± 0.002, r²: 0.9938), α–tocopherol (0.579 ± 0.008,
r²: 0.9508), comfrey–ethanol (0.408 ± 0.028, r²: 0.9494), and
comfrey–water (0.357 ± 0.088, r²: 0.9044). The CUPRAC assay,
known for being cost–effective, stable, selective, and rapid, is
suitable for assessing antioxidants regardless of their hydrophilicity
or chemical structure [27]. The Cu²
+
–reducing capacity of comfrey
extracts and standard compounds is detailed in TABLE I. At the
same concentration (10µg·mL
-1
), the Cu²
+
–reducing ability ranked
as follows: Trolox (0.618 ± 0.066, r²: 0.9994), α–tocopherol
(0.385 ± 0.004, r²: 0.9206), comfrey–ethanol (0.135 ± 0.016,
r²: 0.9047), and comfrey–water (0.129 ± 0.005, r²: 0.9718). A
positive correlation was observed between the samples’ Fe³
+
– and
Cu²
+
–reducing capacities.
The radical scavenging capacities of comfrey extracts were
assessed using DPPH• and ABTS•+ scavenging assays. The
DPPH assay served as a preliminary test for evaluating the free
radical scavenging activity of the extracts. Both comfrey extracts
demonstrated effective DPPH• scavenging properties. As shown
in TABLE I, the IC50 values for DPPH• scavenging activity followed
this order: Trolox (IC50: 13.07 ± 0 µg·mL
-1
) ≈ α–tocopherol (IC50:
13.32 ± 0 µg·mL
-1
) > comfrey–ethanol (IC50: 46.20 µg·mL
-1
) >
comfrey–water (IC50: 69.30 µg·mL
-1
). Similarly, signicant ABTS•+
scavenging activity was observed, as reflected in TABLE I. The IC50
values for ABTS•+ scavenging were ranked as follows: comfrey–
ethanol (IC50: 69.30 µg·mL
-1
) > comfrey–water (IC50: 77.00
µg·mL
-1
). For comparison, α–tocopherol (IC50: 6.66 µg·mL
-1
) and
Trolox (IC50: 6.86 µg·mL
-1
) served as positive controls. A lower
IC50 value indicates stronger scavenging activity, highlighting the
notable electron–donating properties of the comfrey extracts for
neutralizing free radicals. These ndings demonstrate the potent
DPPH• and ABTS•+ scavenging abilities of comfrey extracts.
Antioxidant and wound healing eects of comfrey / Yakan et al.______________________________________________________________________
4 of 8 5 of 8
Macroscopic ndings of the wound
After the operation of burning, the sizes of burning sites were
measured in mm at different time intervals: 1
st
, 7
th
, and 14
th
d,
respectively. On the rst of measurement, the diameter of the burn
was recorded as 15 mm in these groups. The differences between
the changes related to healing of the burning sites between the
7
th
and 14
th
d of measurements were calculated and the healing
rates are given in FIG 1. The one–way ANOVA was used to evaluate
the healing rates of all the groups that were found by measuring
the burning sites on the 1
st
, 7
th
, and 14
th
d and by calculating the
difference between them statistically. Statistical signicance
was found among the groups. The maximum healing rates found
were ordered as follows: group 3 > group 2 > control (FIG. 1).
Additionally, the burning sites were photographed immediately
after the operation of burning and on the 7
th
and 14
th
d of the
experiment, and the changes in the diameter of burns were
recorded (FIG. 1). During the healing process, wound infection was
detected in the wound site in only one of the rats that belonged to
the control group and it was excluded from the study. There were
no other abnormal ndings detected during the study.
Histopathological ndings
Parameters of histopathological lesion and healing of burn are
presented in TABLE II. In the histopathological evaluation of the
case study of the 7
th
d of the experiment that belongs to the control
group, on the surface crust layer, and under this layer, inflammation
was detected. On the 14
th
d, it was seen that on the surface crust
layer, inflammation under this layer and epithelialization had
started (FIGS. 2, A – D). In the histopathological evaluation of the
case sections of the 7
th
d of the experiment that belongs to group2,
it was seen that epithelialization had started (FIGS. 3A and 3B).
It can also be seen that epithelialization continues on the 14
th
d
of the experiment (FIGS. 3C and 3D). In group 3, epithelialization
was completed on the 7
th
d of the experiment (FIG. 4A). Complete
epithelialization was observed (FIG. 4B). Complete epithelialization
and granulation tissue under epithelialization can be seen (FIG. 4C).
Through the 200× magnication, granulation tissue and proliferous
vascular structures are seen (FIG. 4D).
Phenolic compounds play a crucial role in medicinal plants due
to their ability to scavenge free radicals, attributed to their hydroxyl
groups [28]. At a concentration of one milligram each, the water
and ethanol extracts of comfrey contained 20.0 and 27.6 μg of
phenols measured as gallic acid equivalents, respectively. These
compounds are believed to contribute directly to antioxidant
activity [29, 30]. In this study, comfrey’s antioxidant capacity
was evaluated using assays such as Fe³
+
and Cu²
+
reducing power
and free radical scavenging activities (DPPH· and ABTS•
+
assays).
The IC
50
values for DPPH· scavenging were 69.30 µg·mL
-1
(water
extract) and 46.20 µg·mL
-1
, while for ABTS•
+
scavenging they
were 77.00 µg·mL
-1
and 69.30 µg·mL
-1
(ethanol extract). These
results show that comfrey exhibits signicant antioxidant activity,
likely contributing to its wound–healing properties. Overall, this
TABLE I
Determination of reducing power and radical scavenging of the same concentration (10 µg·mL
-1
) of comfrey by ferric ions (Fe
3+
) and
cupric ions (Cu
2+
) reducing capacities and the half maximal scavenging concentration (IC
50
) DPPH• and ABTS•
+
scavenging methods
Antioxidants
Fe
3+
–Fe
2+
reducing* Cu
2+
–Cu
+
reducing* DPPH• scavenging** ABTS•
+
scavenging**
λ
700
R
2
λ
450
R
2
IC
50
R
2
IC
50
R
2
α–Tocopherol 0.579 ± 0.008 0.9508 0.385 ± 0.004 0.9206 13.32 0.8769 6.66 0.8659
Trolox 1.087 ± 0.002 0.9938 0.618 ± 0.066 0.9994 13.07 0.9588 6.86 0.9997
Comfrey–water 0.357 ± 0.088 0.9044 0.129 ± 0.005 0.9718 69.30 0.9113 77.00 0.9605
Comfrey–ethanol 0.408 ± 0.028 0.9494 0.135 ± 0.016 0.9047 46.20 0.9349 69.30 0.9734
*:Theywereexpressedasabsorbancevalues,**
:
TheywereexpressedasIC
50
values
FIGURE 1. *Statistical signicance between group1, group 2, and group 3 (P<0.05),
**: statistical signicance between group 1 and group 2 (P<0.05), #: statistical
significance between group1, group 2, and group 3 (P<0.05), ##: statistical
signicance between group 1 and group 2 (P<0.05)
TABLE II
Histopathological parameters of burn healing on the 7
th
and 14
th
days of study
Histopathological
parameters
Group 1 (control) Group 2 Group 3
Days Days Days
7
th
14
th
7
th
14
th
7
th
14
th
Ulcer +++ +++ +++ ++ +++ +
Inammation +++ +++ +++ ++ +++ -
Epitelization - + ++ +++ +++ +++
Granulationtissue - + + ++ ++ +++
Angiogenesis - + + ++ ++ +++
Ulcer(presence+,absence-),inammation(absence-,mild+,moderate++,intense
+++),epitelization(absence-,mild+,moderate++,intense+++),granulationtissue
(absence-,mild+,moderate++,intense+++),angiogenesis(absence-,mild+,
moderate++,intense+++)
Antioxidant and wound healing eects of comfrey / Yakan et al.______________________________________________________________________
_________________________________________________________________________________________________Revista Cientica, FCV-LUZ / Vol.XXXV
5 of 8
Second–degree and further degrees of burns require medical
attention. The aim of the treatment of burn wounds is quick re–
epithelialization. Burning skin which is the rst barrier against
infections makes the body unguarded against the attacks of
microorganisms. It is a common complication that a burning
wound gets infected and goes into sepsis in the burning cases
[31, 32]. 75% of the causes of the death of the patients who burnt
are infections [33]. It is recommended to use many antiseptic,
antibiotic, and topical antimicrobial agents to protect the wound,
which is open to infections [32, 34]. The most commonly used
topical antimicrobial agent for this purpose is silver sulfadiazine
(1%). It is known that among all medicines that can be used for this
purpose, it is the one that has the least side effects. But when the
re–epithelialization starts in the burning sites, it slows down the
speed of the re–epithelialization. Because of this reason, it shouldn’t
be used at that time [34, 35, 36, 37]. It cannot be penetrated to
study suggests comfrey as a safe traditional treatment option
for burn healing, with its benefits likely stemming from its
antioxidant activity.
Burn that causes morbidity and mortality is one of the severe
traumas with which the body is faced. Burn is a severe health
problem that causes minor injuries treated as ambulatory
treatment, physiological changes in the tissue, hypovolemic,
infection, alteration in body image, organ loss, and even death.
When the skin, which forms a barrier to protect the body, is exposed
to heat between 40–44°C, tissue integrity is damaged and the
burning wound is shaped. Burns are graded according to the types
of agents and the duration of exposure and the treatment is also
planned according to these degrees. First–degree burns that affect
only the epidermis require ambulatory care and therapy. It does
not cause severe complications [31].
FIGURE 2. Histopathological appearance of group 1’ sections taken on the 7
th
and 14
th
days of the experiment, (A) Ulceration and cruts layer are partly detected on
the 7
th
days of the experiment 40× H&E, (B) Active inammation cells (arrow) are seen but regeneration is not seen 200× H&E, (C) Cruts on the surface and partial
epithelialization are observed on the 14
th
days of the experiment 40× H&E, (D) Cruts on the surface and partial epithelialization (arrow) are seen 200× H&E
FIGURE 3. Histopathological appearance of group 2’s sections taken on the 7
th
days and 14
th
days of the experiment. (A) Cruts on the surface and under this surface
partial epithelialization are observed on the 7
th
days of the experiment 40× H&E. (B) Cruts on the surface and under this surface partial epithelialization (arrow) are
seen 200× H&E. (C) Cruts on the surface and partial epithelialization are observed on the 14
th
days of the experiment 40× H&E. (D) Epithelialization area (arrow). There
was partial epithelialization 200× H&E
FIGURE 4. Histopathological appearance of group 3 sections taken on the 7
th
days and 14
th
days of the experiment. (A) Complete epithelialization was observed on the
7
th
day of the experiment 40× H&E. (B) Complete epithelialization was seen 200× H&E. (C) Complete epithelialization and granulation tissue under epithelialization
were seen 40× H&E. (D) Complete epithelialization, granulation tissue under epithelialization and proliferous vascular structures (arrow) can be observed 200× H&E
A
A
A
B
B
B
C
C
C
D
D
D
Antioxidant and wound healing eects of comfrey / Yakan et al.______________________________________________________________________
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eschar, which is a limiting factor in terms of its usage on burning
wounds [11]. Using antibiotics during the treatment of a patient
who is burnt is contradictive [34]. Even though their burning site
is extended, prophylactic antibiotics during the treatment of each
patient shouldn’t be used routinely. By this means, the emergence
of infections that are resistant to antibiotics can be prevented. But
if the patients have both burnt and open wounds and infected and
dirty wounds, they should use prophylactic antibiotics [38].
Infection of the burning site is the most important complication
and necrotic tissue creates a suitable environment for the
reproduction of the microorganisms. To control infection in cases
of burning, it is required to strengthen debridement, which distracts
infarct, strengthens immune response, ensures adequate nutrition,
and uses topical, systemic antimicrobial agents. When most topical
antimicrobials kill pathogens in the burning site, they can also
kill broblasts and keratinocytes, which are reproduced during
the healing period. It causes a delay in the healing of burning
and it increases the risk of infection [36, 37, 38]. Several strong
antimicrobial agents are not suitable for use in the treatment of
burn injuries for a long period because of their cytotoxic effects [39].
In today’s world, modern medicine uses herbs in the treatments,
which have been used traditionally over the centuries [8, 39].
Phototherapeutic agents are used commonly for the healing of
cutaneous wounds [40]. Aloe vera essence, which is one of the
herbal medicines used commonly in the treatment of wounds,
has a lot of bioactive components that enhance wound healing.
Thanks to its certain features such as being a blood flow enhancer,
moisturizer, antimicrobial, and anti–inflammatory, it heals wounds.
It is reported that it can be an effective choice of treatment for rst–
degree and second–degree burns, shortening the time required for
re–epithelialization and the time required for healing [41, 42, 43].
However, some studies are showing that certain substances taken
from Aloe vera have negative effects on angiogenesis [44]. Hypericum
perforatum is commonly used by society for wound treatment. It is
reported that its wound–healing activity results from the increase
in the broblastic activity and synthesis of collagen [45]. However,
it is noted that it inhibits hypericin angiogenesis, which is one of the
active substances of Hypericum perforatum [46].
Comfrey (Symphytum ofcinale) has been used by people since
ancient times to alleviate pain and heal wounds. It is reported that
allantoin, which is found in its structure, enhances the organism’s
immunity, has antioxidant and anti–inflammatory effects, and
accelerates wound healing [8, 9]. Spin–Neto et al. [47] reported in
their study on the effects of Symphytum ofcinale on hematopoietic
strength and bone density in rats that it enhanced bone formation.
In another study by Smith and Jacobson [48], the formulations of
Symphytum ofcinale L. were superior to placebo in reducing pain
and stiffness and improving physical functions in the treatment of
osteoarthritis. In their study, Mulkijanyan et al. [49] recommend
species of comfrey for treating second–degree burns. In the present
study, we compared the effects of the control group, treatments
with vaseline alone, and the combination of vaseline + Symphytum
ofcinale on experimentally induced third–degree burns in rats.
Based on macroscopic and histopathological ndings, wound
healing was faster in the treatment groups compared to the control
group. Among the treatment groups, the vaseline + Symphytum
ofcinale group showed faster wound healing than the Vaseline–
only group. Our ndings support those of previous researchers.
CONCLUSIONS
In this research, we evaluated the effect of Symphytum ofcinale
in the treatment of experimental third–degree burns in rats.
Macroscopic and histopathological ndings show that the wound
heals more rapidly in the Symphytum ofcinale + vasaline group
than in the the others groups. According to the results of our
research using comfrey, which has antioxidant properties medicinal
plants, and comfrey enhances the healing of experimental third–
degree burns in rats.
Financial support
This study was not nancially supported by any institution
or organization.
Conflict of interest
The authors state that they have no conflicts of interest.
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