UNIVERSIDADE ESTADUAL PAULISTA

“JÚLIO DE MESQUITA FILHO”

Instituto de Ciência e Tecnologia

Campus de São José dos Campos

ORIGINAL ARTICLE DOI: https://doi.org/10.4322/bds.2023.e3853

Braz Dent Sci 2023 July/Sept;26 (3): e3853

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Efeito de reparação tecidual de uma semana de enxaguante bucal de Aloe Vera: um estudo piloto

Basima Gh. Ali1 , Hadeel Mazin Akram1 , Sarah A. Abed2 , Farah Sabah Rasheed2 

1 - University of Baghdad, Collage of Dentistry, Department of Periodontology. Baghdad, Iraq.

2 - Iraqi Ministry of Health. Baghdad, Iraq.

How to cite: Ali BG, Akram HM, Abed SA, Rasheed FS. Wound healing effect of a one-week Aloe Vera mouthwash: a pilot study.

Braz Dent Sci. 2023;26(3):e3853. https://doi.org/10.4322/bds.2023.e3853

ABSTRACT

Aloe Vera, a perennial Liliaceae plant, has medical, cosmetic, and wound-healing properties. Aloe vera has antioxidant,

anti-cancer, anti-diabetic, and regenerative effects. Glucommannan increases collagen synthesis and aids healing after

ginivectomy treatment. Natural mouthwashes may offer gingival wound healing efcacy with reduced side-effects

when compared to Chlorhexidine. Objective: the objective of this clinical study was to compare the effects on wound

healing of a one-week Aloe vera mouthwash with chlorhexidine mouthwash before gingivectomy surgical therapy.

Material and Methods: a total of 45 individuals experiencing inammatory gingival enlargement were included in the

study. They underwent professional mechanical plaque removal and were then randomly divided into three groups.

In group I, comprising 15 patients, participants were advised to utilize 100% Aloe vera juice as a mouthwash twice

daily. Group II, also consisting of 15 patients, was instructed to use Chlorhexidine (0.2%) mouthwash twice daily.

The Control group, which consisted of 15 patients, was recommended to use a placebo mouth rinse in addition to

mechanical plaque removal. During the second visit, which occurred one week after the initial visit, the enlarged gingival

tissue was surgically removed through scalpel gingivectomy. Immunohistochemical (IHC) analysis was performed on

the excised tissue to measure the levels of broblast growth factor-2. Results: when compared to the control group,

Aloe vera showed signicant differences regarding the expression of broblast growth factor-2(FGF-2), and highly signicant

differences in angiogenesis. At the same time, there were substantial differences in angiogenesis with no signicant

differences in the expression of FGF2 between Chlorhexidine and control groups. Conclusion: aloe vera has exhibited

potential wound-healing effects as it signicantly affected the IHC expression of FGF2 and angiogenesis when used

as an adjunct to plaque control before gingivectomy surgical therapy.

KEYWORDS

Aloe-vera; Fibroblast growth factor-2; Gingival overgrowth; Chlorhexidine; Mouthwash.

RESUMO

Aloe Vera, uma planta perene de Liliaceae, tem propriedades médicas, cosméticas e cicatrizantes. Aloe vera

tem efeitos antioxidantes, anticancerígenos, antidiabéticos e regenerativos. O glucomanano aumenta a síntese

de colágeno e auxilia na cicatrização após o tratamento de gengivectomia. Enxaguatórios bucais naturais

podem oferecer ecácia na reparação de feridas gengivais com efeitos colaterais reduzidos quando comparados

à clorexidina. Objetivo: O objetivo deste estudo clínico foi comparar os efeitos na cicatrização de feridas de

uma semana de enxaguatório bucal de Aloe vera com clorexidina antes da terapia cirúrgica de gengivectomia.

Material e Métodos: um total de 45 indivíduos com aumento gengival inamatório foram incluídos no estudo.

Eles foram submetidos à remoção mecânica prossional da placa e foram divididos aleatoriamente em três

grupos. No grupo I, composto por 15 pacientes, os participantes foram orientados a utilizar 100% de suco

de Aloe vera como enxaguante bucal duas vezes ao dia. O grupo II, também composto por 15 pacientes, foi

instruído a usar enxaguante bucal com clorexidina (0,2%) duas vezes ao dia. O grupo controle, composto

por 15 pacientes, foi recomendado o uso de enxaguatório bucal placebo além da remoção mecânica da placa.

Braz Dent Sci 2023 July/Sept;26 (3): e3853

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

INTRODUCTION

Regardless of gender, age, or ethnicity, over

90% of individuals experience gingivitis caused

by plaque, making it one of the most prevalent

periodontal conditions [1]. Gingivitis is initiated

by the noxious substances resulting from the

deposition of microbial plaque at or close to the

gingival sulcus [2].

Oral hygiene adjuncts, such as mouth rinses,

are commonly utilized as anti-plaque agents [3],

and also act as vehicles to deliver active agents to

the teeth and gingiva [1]. According to a review,

there is strong evidence supporting the effectiveness

of chlorhexidine (CHX) mouthwash in reducing

gingivitis and plaque levels among patients with

mild to moderate disease. However, there is

moderate evidence suggesting that prolonged use

of CHX mouthwash can lead to external staining

of teeth. Furthermore, the prolonged usage of

chlorhexidine (CHX) mouthwash is discouraged

due to several side effects, such as brown staining

of teeth and tongue, altered taste sensation, and

increased calculus formation [4]. Hence, there is

a need to develop natural products and domestic

and economic oral hygiene aid. Aloe vera extract

could be one such plaque control aid [1].

Aloe vera, belonging to the Liliaceae family,

is a cactus-like plant known for its gel-like

mucilaginous tissue. This gel has been traditionally

used as a laxative and for the treatment of various

conditions, including sunburn, wounds, and

digestive tract disorders [5]. Pharmacological

attributes of Aloe vera show that it acts as an

antibacterial, antiviral, antifungal, antioxidant,

and anti-inammatory [6]. Upon oral or topical

administration, a specic active ingredient found

in Aloe vera stimulates the proliferation and

activity of broblasts. This stimulation, in turn,

affects the composition of collagen, particularly

an increase in type III collagen. Additionally,

there is an enhancement in collagen synthesis and

cross-linking, which contributes to the process of

wound contraction [7]. A study done by Abed and

Al-Hijazi in 2016 used Aloe vera gel in periodontal

defects related to its ability to accelerate wound

healing as it increases syndecan 1 expression in

epithelial cells, precursor progenitor cells and in the

early stage of cell proliferation of the mesenchymal

cell, inammatory cells, and cementoblast [8].

Aloe vera contains approximately 75 potentially

active components, including water, sugars, enzymes,

lignin, vitamins, amino acids, and minerals [9]. One

of these compounds is glucomannan, a growth

hormone and mannose-rich polysaccharide; it

interacts with growth factor receptors on the

fibroblast to activate proliferation and increase

collagen synthesis [10]. Aloe vera may change

collagen composition (increasing type III collagen),

improve collagen cross-linking [11] and increase

the amount of collagen in wounds thereby promote

wound healing [12]. Prior studies on aloe vera gel

have indicated that it has the potential to decrease

skin fragility and enhance skin flexibility [13].

In a study that was done on rats; following oral

and topical treatment with aloe-vera, an increase

in the synthesis of hyaluronic acid and dermatan

sulfate in the granulation tissue of a healing wound

has been seen [14].

Growth factors are natural biological

mediators responsible for regulating important

events in the cell, including the tissue-repairing

process by binding to a specic receptor on the

cell’s surface [15].

Fibroblast growth factors (FGFs) are a group

of growth factors known for their involvement

in angiogenesis, wound healing, and embryonic

development. Specically, FGF-2 plays a crucial

role by promoting the proliferation of broblasts

and osteoblasts, as well as enhancing angiogenesis.

Durante a segunda visita, que ocorreu uma semana após a visita inicial, o tecido gengival aumentado foi removido

cirurgicamente por meio de gengivectomia com bisturi. A análise imuno-histoquímica (IHC) foi realizada no tecido

excisado para medir os níveis do fator de crescimento de broblastos-2 (FGF-2). Resultados: quando comparado

ao grupo controle, o Aloe vera apresentou diferenças signicativas em relação à expressão do FGF-2, e diferenças

altamente signicativas na angiogênese. Ao mesmo tempo, houve diferenças substanciais na angiogênese, sem

diferenças signicativas na expressão de FGF-2 entre a clorexidina e os grupos controle. Conclusão: Aloe vera

exibiu potenciais efeitos de cicatrização de feridas, pois afetou signicativamente a expressão IHC de FGF-2 e a

angiogênese quando usada como adjuvante no controle de placa antes da terapia cirúrgica de gengivectomia.

PALAVRAS-CHAVE

Aloe Vera; Fator 2 de crescimento de broblastos; Crescimento excessivo da gengiva; Clorexidina; Antissépticos Bucais.

Braz Dent Sci 2023 July/Sept;26 (3): e3853

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

These activities have a direct association with

the regeneration of periodontal tissues [16].

Some efcacy can be expected from FGF- 2 in

stimulating the regeneration of periodontal tissue

in patients having periodontitis [17].

Only a few studies have been conducted

to assess and compare the effects of Aloe

vera and chlorhexidine on the expression of

broblast growth factor-2 (FGF-2) [18,19], so

it was eventually needed to carry out this study

to study and compare the effects on wound

healing between Aloe-vera and chlorhexidine

mouthwashes when used one-week before

gingivectomy.

MATERIALS, METHODS AND SUBJECTS

Sample/study design

This pilot study adhered to the guidelines

outlined in the 1975 Helsinki Declaration, revised

in 2013, and received approval from the ethical

committee of the University of Baghdad. Prior

to participation, each subject provided informed

consent, acknowledging their understanding

of the study’s objectives and their freedom to

withdraw at any time. The study was conducted at

the teaching hospital of the College of Dentistry,

University of Baghdad, spanning from September

2019 to July 2020.

Inclusion criteria

To be included in the study, patients had to

meet the following criteria:

• Being systemically healthy, with an age

range between 15 and 30 years old;

• Not having used any medication within the

past three months;

• Having inammatory gingival enlargement;

• Not having any known allergy to chlorhexidine

or aloe vera.

Exclusion criteria

Exclusion criteria for the study are as

follows:

• Patients with systemic conditions such as liver

and/or kidney dysfunction, inflammatory

bowel disease (e.g., Crohn’s disease), diabetes

mellitus, a history of organ transplant or cancer

treatment, or cardiovascular disease;

• Patients who have undergone extensive

periodontal therapy in the past or are currently

undergoing active periodontal therapy;

• Patients who have taken immunosuppressive

drugs or antibiotics within the previous three

months;

• Patients who have gingival enlargements not

caused by inammation;

• Patients with a known allergy to aloe vera

or chlorhexidine.

Blinding and randomized

For the intervention assignment in this study,

a computer random number generator (such as the

one available in Microsoft Excel) was used. Each

participant had an equal chance of being assigned

to one of the interventions. The study involved three

different compounds: aloe vera juice (test group),

0.2% chlorhexidine (control group), and distilled

water with avors (placebo group).

To ensure blinding and allocation concealment,

an independent dentist who was not involved

in the study assigned sequential number codes

(1, 2, and 3) to identical, opaque bottles containing

the mouthwashes. This process ensured that neither

the examiner nor the participants could identify

the interventions contained in the opaque bottles.

After the study concluded, the decoding of the

interventions took place.

The examiner received the blinded

interventions according to a predetermined

sequence list of interventions identied by numbers.

This methodology ensured a double-blinded trial,

where both the examiner and the participants

were unaware of which interventions were being

administered until the decoding process occurred.

Study sample and grouping

In this study, a total of 45 subjects (13 males,

32 females) with inammatory gingival enlargement

and an age range of 15 to 30 years participated.

During the rst phase of periodontal treatment,

which included motivation, oral hygiene instructions,

scaling, and polishing, the patients underwent

the necessary procedures. Plaque index (PI) and

gingival index (GI) were measured for the patients

to ensure that plaque control was satisfactory to

proceed to the surgical phase. For gingivectomy,

a plaque index of less than 0.5 was deemed

suitable. Afterward, the participants were randomly

assigned one of the mouthwash bottles labeled as

Braz Dent Sci 2023 July/Sept;26 (3): e3853

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Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

No. 1, No. 2, or No. 3. These 45 participants were

examined and assisted by the same professional

dental examiner who underwent intra and inter

examiner calibrations to ensure taking the right

measurements of the parameters. The assessment

of inter- and intra-examiner calibration for (PI)

and (GI) was conducted by the utilization of the

kappa-coefcient assay. A kappa value of ≥75%

was established as the threshold for determining

the presence of a satisfactory level of agreement.

The subjects were instructed to rinse their

mouths with the assigned mouthwash for one

minute, twice daily, over a period of seven days.

Grouping

The participants in the study were divided

into three groups as follows:

Study Group I (Aloe vera group): Consisting of

15 patients who used aloe vera mouthwash.

The mouthwash used in this group was made

of 100% pure aloe vera juice.

The subjects were instructed to rinse their

mouths with 10 ml of it for one minute, twice

daily, over a period of seven days.

Study Group II (CHX group): Comprising

of 15 patients who used chlorhexidine

mouthwash (0.2%) and rinse with 10 ml of

it for 1 minute, twice daily for seven days.

This group served as the positive control.

Control Group: Including 15 patients who used

a mouthwash made of distilled water with

avors. The same instructions were given

to this group too. This group served as the

placebo or negative control in the study.

All the participants were instructed to rinse

after 30 minutes from brushing and to restrain

from eating and drinking for another 30 minutes

after rinsing.

During the second visit, after a period of 7 days,

the gingival tissue of patients who underwent

conventional gingivectomy was carefully excised

using a surgical scalpel. Following the excision,

a periodontal dressing was applied to cover the

surgical area for protection. The excised gingival

tissue was then washed with normal saline to

remove any debris or contaminants. Subsequently,

the tissue samples were xed using a 10% formalin

solution to preserve their structure for subsequent

histological evaluation. In addition to histological

evaluation, immunohistochemical analysis of

the basic fibroblast growth factor (FGF-2) was

performed on the xed gingival tissue samples.

This analysis aimed to study the presence and

distribution of FGF-2 in the excised gingival tissue

samples.

Tissue preparation and staining

Sections: From each of these parafn-embedded

tissue blocks; serialized sections of 4μm were

cut as follows:

· Sections were mounted on standard glass

slides, stained with Hematoxylin and

Eosin (H&E), and histopathologically

re-evaluated by an experienced pathologist;

· One section for each case was cut and

mounted on positively charged slides for

Immunohistochemistry (IHC) staining

with broblast growth factor-2 (FGF-2)

polyclonal antibodies;

· For each immunohistochemistry run,

one slide of positive controls (Figure 1)

and one negative control slide were

included.

Histomorphometric analysis

After the tissue sections were prepared

on slides, the following steps were taken for

immunohistochemical analysis:

1. Slide baking: The slides were baked at 60°C

overnight to ensure proper adhesion of the

tissue sections to the slides;

Deparafnization: The slides were deparafnized

by immersing them in three changes of xylene

for 10 minutes each. This step removes the

parafn wax from the tissue sections;

Figure 1 - IHC staining of hepatocellular carcinoma (40X).

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Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

3. Hydration: The slides were then hydrated

by sequentially immersing them in a series

of alcohol solutions and distilled water.

Each immersion lasted for 5 minutes. This

process gradually removes the alcohol and

rehydrates the tissue sections;

4. Heat-induced epitope retrieval (HIER): The

tissue sections underwent heat-induced

epitope retrieval by subjecting them to heat at

a temperature of 95-99°C for 20 minutes. This

step helps to unmask the epitopes, making

them more accessible for antibody binding;

5. Cooling: After HIER, the slides were allowed

to cool down at room temperature for a

minimum of 20 minutes;

6. Blocking endogenous peroxidase activity: The

slides were treated with a peroxidase-blocking

reagent for 10 minutes. This step prevents

endogenous peroxidase activity, which can

interfere with the immunohistochemical

staining;

7. Washing: The slides were rinsed with a

washing buffer to remove any residual

reagents or debris;

8. Primary antibody incubation: The primary

antibody (or washing buffer for a negative

control) was added to the slides and incubated

for 30 minutes at 37°C. This step allows the

primary antibody to bind to the target antigen

in the tissue sections;

9. Washing: The slides were rinsed again with

the washing buffer to remove unbound

primary antibody;

10. Enhancer treatment: An enhancer solution

was added to the slides and incubated

for 20 minutes. This step enhances the

immunohistochemical staining signal;

11. Washing: The slides were rinsed once more

with the washing buffer;

12. DAB incubation: The prepared DAB

(3,3’-diaminobenzidine) solution, which

produces a brown color when reacting with the

peroxidase enzyme, was added to the slides

and incubated for 10 minutes;

13. Washing: The slides were rinsed again with

the washing buffer to remove excess DAB;

14.

Counterstaining: The slides were counterstained

with hematoxylin for 10 seconds. Hematoxylin

imparts a blue color to the cell nuclei;

15. Washing: The slides were rinsed with tap

water to remove excess counterstain;

16. Dehydration: The slides were dehydrated

by immersing them in a series of alcohol

solutions and two changes of xylene. This step

removes water and ensures proper mounting;

17. Mounting: The nal step involved mounting

the slides with DPX, a mounting medium,

and covering them with coverslips. DPX

helps to preserve the stained tissue sections

and provides optical clarity.

Once the mounting is complete, the slides

are ready for examination under a microscope.

Immunohistochemical signal specicity was

demonstrated by the absence of immunostaining

in the negative control slides and its presence in

recommending positive controls. For FGF-2, cells

with clear brown cytoplasmic staining patterns

were considered positive. The extent of staining

was scored using the following scale:

Score 0 = 0-10% of cells (negative),

Score I = staining 10-25% of cells (weak positive),

Score II = staining 25-50% of cells (moderate

positive), and Score III = staining up to 50% of

cells (strong positive) [20].

Also, the number of newly formed blood

vessels (angiogenesis) was calculated and

compared between the groups [21].

Statistical analysis: the statistical analysis

was done by SPSS by the use of Descriptive and

inferential statistic and Multiple Mann-Whitney U

test (Bonferroni method) with the P value <0.05.

RESULTS

Tables I and II show descriptive and statistical

analysis of matrix FGF2 at the second visit. The

median in Aloe-vera and CHX groups was 2,

whereas, in the control group, it was 1, with

signicant differences among groups as the p-value

(0.021). The intergroup comparison in matrix

FGF2 at second visits shows a signicant difference

between Aloe-vera and control groups. At the same

time, there was no signicant difference between

CHX and control groups and between CHX and

Aloe-vera groups (Figures 2, 3, 4, 5, 6 and 7).

Regarding the angiogenesis; The Aloe-vera

group had the highest median value of angiogenesis

at 24, followed by the CHX group with a median of 22.

The control group had the lowest mean value of

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Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

angiogenesis at 15 indicating less angiogenesis

compared to the other two groups (Table III).

When comparing the angiogenesis levels between

the groups at the second visits, there was a highly

signicant difference between the Aloe-vera group

and the control group. There was also a signicant

difference observed between the CHX group

and the control group. However, no significant

difference was found between the CHX group and

the Aloe-vera group (Table IV).

These ndings are summarized in Table III.

Additionally, Figures 2, 3, 4, 5, 6, and 7 may provide

visual representations of the data or further analysis

related to angiogenesis in the different groups.

Table I - Descriptive and inferential statistic of matrix FGF2 at 2nd visit for all groups

Statistics Control CHX Aloe-vera

Descriptive

N 15 15 15

Minimum 1.000 1.000 1.000

Maximum 3.000 3.000 3.000

Median 1 2 2

Mean rank 16.96 21.30 28.87

Kruskal-Wallis

Chi-square 7.714

df 2

P-value 0.021(Sig.)

Sig. = Signiﬁcant at P<0.05; df = degree of freedom.

Table II - Multiple Comparisons of Matrix FGF2 at the second visit

(I) Groups (J) Groups

Multiple Mann-Whitney U test (Bonferroni method)

Z Sig.

Control CHX -0.996 0.957 NS

Aloe-vera 2.734 0.018 Sig.

CHX Aloe-vera 1.769 0.231 NS

Sig. = Signiﬁcant at P<0.05; NS = Non-signiﬁcant; Z: z-score

Table III - Descriptive and inferential statistic angiogenesis at 2nd visit for all groups

Statistics Control CHX Aloe-vera

Descriptive

N 15 15 15

Minimum 7.000 11.000 18.000

Maximum 30.000 36.000 37.000

Median 15 22 24

Mean rank 13.39 24.83 28.67

Kruskal-Wallis

Chi-square 11.034

df 2

P-value 0.004 (HS)

HS = High Signiﬁcant at P<0.01; df = degree of freedom.

Table IV - Multiple Comparisons of angiogenesis at the 2nd visit

(I) Groups (J) Groups

Multiple Mann-Whitney U test (Bonferroni method) Descriptive and inferential statistic

Z Sig.

Control CHX 2.402 0.048 Sig.

Aloe-vera 3.206 0.003 HS

CHX Aloe-vera 0.819 1.00 NS

HS = High Signiﬁcant at P<0.01; Sig. = Signiﬁcant at P<0.05; NS = Non-signiﬁcant. EZ = t/√N, 0.2 = small, 0.5 medium, 0.8 Large; Z: z-score.

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Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Figure 2 - IHC staining for Aloe-vera case (20X).

Figure 3 - IHC staining for Aloe-vera case (40X).

Figure 4 - IHC staining for CHX case (20X).

Figure 5 - IHC staining for CHX case (40X).

Figure 6 - IHC staining for control case (20X).

Figure 7 - IHC staining for control case (40X).

DISCUSSION

The findings of this study suggest that

the wound-healing capacity of Aloe vera may

contribute to these observed differences. Aloe

vera has been studied for its wound healing

properties in various research studies. For

example, Davis et al. [22] conducted a study that

highlighted the wound-healing ability of Aloe

vera. Aloe-vera was found to increase oxygenation

by promoting angiogenesis, which is the growth

of new blood vessels. This increased blood ow to

the wound, leading to improved oxygen supply.

The study utilized a rat model and demonstrated

that Aloe vera accelerated wound closure and

enhanced the tensile strength of the wounds.

Overall, the signicant differences observed

in the study’s results between the Aloe-vera

group and the control group, as well as the

observed angiogenesis, may be attributed to the

wound-healing properties of Aloe vera [22].

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Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

In vitro and in vivo studies have demonstrated

the positive effects of Aloe vera extract on broblast

proliferation. Glucomannan, an active ingredient

found in Aloe vera, has been shown to promote

increased collagen synthesis by interacting with the

broblast growth factor receptor (FGFR), thereby

stimulating broblast activity. A study conducted by

Zhi et al. [23] investigated the effects of glucomannan

extract derived from Aloe vera on fibroblast

proliferation and migration. The results of the study

revealed that glucomannan extract increased the

proliferation and migration of broblasts, which are

critical cells involved in the process of wound healing.

Based on their ndings, the authors suggested that

glucomannan may hold promise as a potential

wound healing agent due to its ability to enhance

broblast activity. These studies support the notion

that Aloe vera, specifically its active component

glucomannan, can positively inuence broblast

function and collagen synthesis, which are essential

processes for effective wound healing [23]. Aloe

vera gel polysaccharide acemannan has also been

shown to have a signicant role in wound healing.

Acemannan activates macrophage proliferation,

which is important for the body’s immune response

to injury. In a rodent model, the authors of the

study discovered that acemannan promoted wound

healing; these findings suggest that acemannan

could be used as a potential healing agent [24].

In a study conducted by Sargowo et al. [25], the

researchers investigated the effects of Aloe vera

gel on angiogenesis in diabetic patients. The study

revealed that Aloe vera gel played a signicant role

in promoting angiogenesis. Specically, it enhanced

the activity of endothelial progenitor cells (EPCs),

reduced the levels of circulating endothelial cells

(CECs), and increased the expression of vascular

endothelial growth factor (VEGF) and endothelial

nitric oxide synthesis (eNOS). The findings of

the study suggested that Aloe vera gel has the

potential to improve wound healing in diabetic

patients by stimulating angiogenesis. Angiogenesis,

the formation of new blood vessels, is crucial for

delivering oxygen and nutrients to the wound

site, as well as for removing waste products. By

promoting angiogenesis and increasing blood

flow to the wound, Aloe vera gel may facilitate

the healing process in individuals with diabetes.

These results support the use of Aloe vera gel as a

potential therapeutic option for enhancing wound

healing in diabetic patients, due to its ability to

promote angiogenesis and improve blood circulation

to the wound area [25].

For future studies, we suggest doing mechanistic

studies to investigate the underlying mechanisms

by which Aloe-vera affects FGF-2 expression and

angiogenesis. This could involve in vitro studies using

cell culture models or animal studies to explore the

molecular pathways involved in the wound healing

properties of Aloe vera.

Regarding the limitation of this study, this

study had a relatively small sample size, which

may limit the generalizability of the ndings and

also the study has a short duration of intervention.

Longer intervention periods could provide a more

comprehensive understanding of the sustained

effects of Aloe-vera.

CONCLUSION

Aloe vera significantly has affected the

immunohistochemical expression of FGF2 and

angiogenesis in gingival tissue, which may

explained the wound healing effects of Aloe

vera. It can be used as might be considered a

potential alternative to Chlorhexidine, especially

in low socio-economic status populations. Further

randomized controlled studies are necessary to

investigate these ndings.

Author’s Contributions

BGA: Review & Editing, Supervision, Methodology.

HMA: Review & Editing, Software, Writing. SAA:

Conceptualization, Formal Analysis, Investigation,

Resources, Data Curation, Writing – Original Draft

Preparation, Writing – Review & Editing. FSR:

Visualization, Supervision, Project Administration.

Conict of Interest

There is no interest of coniction.

Funding

This study is self-funded.

Regulatory Statement

We certify that this study involving human

subjects is by the Helsinki declaration of 1975, as

revised in 2013 and that the relevant institutional

ethics committee has approved it. The protocol

number is 41 in 5-3-2019.

This clinical trial emphasizes on the wound

healing effects of Aloe vera on gingival tissue so; it might

Braz Dent Sci 2023 July/Sept;26 (3): e3853

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

Ali BG et al.

Wound healing eﬀect of a one-week Aloe Vera mouthwash: a pilot study

be considered a potential alternative to Chlorhexidine

(CHX); and an alternative to CHX as an adjunct to

mechanical plaque control before gingivectomy,

especially in low socio-economic status population.

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Hadeel Mazin Akram

(Corresponding address)

University of Baghdad, Collage of Dentistry, Department of Periodontology,

Baghdad, Iraq.

Email: Hadeel.mazin@codental.uobaghdad.edu.iq

Date submitted: 2023 Apr 05

Accept submission: 2023 Aug 17