CHAPTER 1

PRELIMINARY

1. Background
Periodontitis is inflammation of the supporting tissues of the teeth caused
by groups of specific microorganisms, resulting in progressive damage to the
periodontal ligaments and alveolar bone and is characterized by increased probing
depth, loss of attachment and alveolar bone damage (Newman, 2012: 160). The
pathogenesis of periodontal disease is an inflammatory process involving the
natural immune response and adaptive immune. Phagocyte cells, such as
polymorphonuclear neutrophils, monocytes, and macrophages which are natural
immune cells will trigger the release of chemical mediators such as cytokines
(Tumor Necrosis Factor / TNF and Interleukin / IL) that activate various systems
such as the complement system and phase response acute (Newman, 2012: 249-
251).
       Treatment for periodontitis includes mechanical therapy, ie cleaning the tartar
by scaling and rootplaning with the aim of removing hard and soft deposits that
attach to the surface of the teeth and roots of the teeth as a place for bacterial
colonization (Farjana, 2014: 1). But in deep pockets, mechanical debridement is
often difficult and requires additional therapy including systemic and local
antibiotics (Jaswal, 2014: 1-2).

The weakness of antibiotic use is the presence of side effects on patients,

such as gastric problems, hematology, neurology, dermatology, allergies and the
occurrence of bacterial resistance (Nandini, 2012: 1-2). Therefore, it is necessary
to develop innovative strategies to reduce periodontal pathogens with more
minimal side effects. One strategy that can be done is by exploring medicinal
plants that are widely available in nature (Izui, 2016: 83).

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 Mangosteen (Garcinia mangostana L.) is a tropical tree native to Southeast
Asia that is very popular in Indonesia. Mangosteen, which is synonymous with the
nickname of the tropical fruit queen (Queen of tropical fruit), is a plant that can all
be utilized, including the skin of its fruit (Komansilan, 2015: 309). Some studies
show mangosteen peel turns out to contain ingredients that have higher
pharmacological properties compared to other parts of the mangosteen plant,
although often the mangosteen peel is always thrown into garbage. The skin of the
mangosteen fruit in general has also been used by the community as a traditional
anti-inflammatory drug (Prasetya, 2014: 174).

A number of in vitro studies have shown the skin of mangosteen fruit to

contain a family of tricyclic isoprenylation polyphenols or commonly referred to
as xanton. Xanton is the most important antioxidant component in the mangosteen
peel, where xaanton content on the skin of the mangosteen fruit is 27 times more
than that contained in the mangosteen flesh (Komansilan, 2015: 310). The most
abundant xanthones in mangosteen peel are α- and γ-mangostin. Xanton has
antioxidant effects, is anti-inflammatory, anti-carcinogenic and antimicrobial
(Prasetya, 2014: 174).
Chen et al. 'S results as quoted by Prasetya in 2014 state that alpha
mangostin (α-mangostin) significantly inhibits the production of Nitric Oxide
(NO), Prostaglandin E2 (PGE2), Tumor Necrosis Factor-α and inducible NOS
(iNOS) in RAW 264.7 cells induced lipopolysaccharide. The research by
Nakatani et al. As cited by Prasetya in 2014 also shows Gamma mangostin (γ-
mangostin) acts as an anti-inflammatory with the chemical formula 1,3,6,7-
tetrahidroxy-7, tetrahidroxy-2,8-bis (3-methyl-2butenil) -9H-xanten-9-on.
Decreasing the amount of PGE2 through COX-2-inhibitors can inhibit
inflammation in periodontal disease (Prasetya, 2014: 174).
The local drug distribution system that is usually given through topical
application to eliminate inflammation in the periodontal pocket allows therapeutic
agents to directly reach the target area. This system provides benefits such as low
dosage required, reducing systemic absorption so as to minimize the occurrence of
side effects and concentration

2
the high can be maintained on the applied side so that the drug works more
optimally. Various forms of material have been introduced as topical therapeutic
agents in periodontal treatment including irrigation materials such as liquids and
gels (Jaswal, 2014: 2). But the disadvantage of this material is that it cannot last
long in the pocket because of its liquid physical properties which reduces its
activity and requires multiple applications, the ability and compliance of the
patient in applying it. For this reason, a form of topical therapeutic agent is needed
that can last for a long time in the periodontal pocket area so that it can guarantee
its effectiveness.
The use of chips as a treatment for periodontal pockets has been widely
proposed to be effective in various clinical studies. Jeffcoat et al., As cited by
Soskolne in 2003 regarding the application of Chlorhexidine chip (CHX chip)
after scaling and root planing treatment has shown a reduction in clinical pocket
depth, bleeding on probing and clinical attachment compared to the treated side
only by scaling and root planing after 6-9 months of treatment.
The presence of pharmacological properties on the mangosteen peel as
well as the anti-inflammatory activity of the womb shows the possibility of using
mangosteen peel extract as a topical therapeutic agent for additional therapy in
periodontal disease and the need for long-lasting forms of topical therapeutic
agents in the periodontal pocket region causing authors to be interested in
suggesting innovations regarding the use of mangosteen peel extract chips as a
support therapy in the treatment of periodontitis.

1.2 Problem Formulation

How is the effectiveness of using the mangosteen peel extract chip as a support
therapy in the treatment of periodontitis.

1.3 Creative Ideas

The author's creative idea is to develop treatment for periodontal disease and
increase the effectiveness of the use of herbal medicines in periodontal therapy.
So far many people have looked

3
one eye contains the content of mangosteen skin, so that every time consuming
mangosteen, the skin is always thrown away and eventually becomes waste. A
new innovation is chip making which has the composition of mangosteen peel
extract which is rich in xanton and antioxidants so that it can increase the
effectiveness of treatment of diseases and trigger an increase in reuse of
mangosteen peel waste properly. This certainly will be a new innovation in the
world of health, especially in the field of dentistry and will encourage the
industrialization of mangosteen peel waste processing to advance sustainable
development.

1.4 Purpose of Writing

The purpose of writing this scientific paper is to discuss the effectiveness of using
the mangosteen peel extract chip as a support therapy for the treatment of
periodontitis.

1.5 Benefits of Writing

The benefits of writing scientific papers are to provide information about new
treatments in the field of dentistry and the use of nutritious herbal ingredients,
namely the mangosteen peel, especially as a therapy in the field of dentistry. In
addition, this scientific work is also expected to be an innovation in the
management of mangosteen peel waste from useless material into material that
has economic value.

1.6 Method of Library Studies Conducted

The library study method carried out in writing scientific papers is to collect data
from textbooks and research results from scientific journals. Next is the
assessment, selection, and search for solutions to the problems faced, as well as
drawing conclusions.

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 CHAPTER 2
LITERATURE REVIEW

2.1. Mangosteen Fruit, Composition and Benefits

Taxonomically mangosteen fruit (Garcinia mangostana L.) includes
Spermatophyta division, Angiospermae class, Thalamiflora family Guttiferae
family and Garacinia genus. The mangosteen is round and old-colored because it
contains a lot of anthocyanin on its skin.

Figure 1. Mangosteen fruit

Mangosteen fruit is considered very special, the color of the mangosteen

skin is blackish red, the flesh is pure white and tastes sweet, and the compounds
that are excellent for the fruit are xanton, which is a natural chemical substance
classified as polyphenolic, which is produced by secondary metabolites. Xanton is
not found in other fruits, therefore the mangosteen is called the queen of fruits. In
addition, the mangosteen also contains catechins, potassium, calcium, phosphorus,
iron, vitamin B1, vitamin B2, vitamin B6, and vitamin C. The composition of the
nutritional value of mangosteen fruit can be seen in Table 1. The results of Kasma
Iswari (2005) and a number of other studies show that the largest component of
the whole mangosteen fruit is the skin, which is 70-75%, while the fruit flesh is
only 10-15% and the seeds are 15-20%.

Table 1. Composition of Mangosteen Nutritional Value per 100 Gram

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 Tabel 1. Komposisi Nilai Gizi Buah Manggis per 100 Gram
Value Unit Satuan Nilai
Composition
Water g 70-80
Protein g 0,5
Fat g 0,6
Carbohydrate g 5,6
Calcium Mg 5,7
Phosphor Mg 9,4
Iron Mg 0,3
Vitamin B1 Mg 0,06
Vitamin B2 Mg 0,04
Vitamin C Mg 35
Xanton fruit peel Mg 107,76
Xanton fruit flesh Mg 29,00
Energy Kkal 63

Based on its structure, xanthones are classified as simple aromatic

compounds, such as dibenzofuran, dibenzopyran, and griseofulvin. The
characteristic of this group is the presence of the nucleus dibenzo-γ-pyron which
shows the close relationship between xanthons and flavonoids and chromomers, γ-
pyron derivatives. The free xanton nucleus is a colorless needle crystal, but rarely
found in nature. While what is often found is the derivative form of the oxygens,
so that generally xanthone is isolated in the form of yellow needle crystals.
Xanton and its derivatives can be isolated from fruit peel pericarp in the form of
3-isomangostin, alpha-mangostin, betamangostin, gamma-mangostin, garcinone
A, garcinone B, garcinone C, garcinone D, maclurin, and mangosthenol.
In the human body xanton functions as an antioxidant, antiproliferation,
anti-inflammatory, and antimicrobial. Xanton is a powerful antioxidant, which is
needed for balancing prooxidan in the body and the environment, which is known
as free radicals. Some researchers explain, mature mangosteen skin contains
polyhydroxyxanton, which is a derivative of mangostin and ß-mangostin, which

6
functions as an antioxidant, antibacterial, antitumor, and anticancer. The
antioxidant properties of xanton exceed vitamin E and vitamin C, which have
been known as high levels of antioxidants.

Nakatani et al (2002) stated that from the results of his research with
mouse cells that 5 micrograms of gamma-mangostin was able to stop
inflammation by inhibiting the production of the enzyme cyclooxygenase -2
which causes inflammation. In fact, gamma-mangostin has a better anti-
inflammatory effect than anti-inflammatory drugs on the market. In 2002,
scientists at the National Research Institute of Chinese Medicine in Taiwan
discovered the efficacy of garcinone E (xanton derivatives) which was very
effective in inhibiting liver cancer, gastric cancer, and lung cancer. The efficacy of
garcinone E is far more effective at inhibiting cancer cells when compared to
cancer drugs such as flauraucil, cisplatin, vincristin, metohotrexete, and
mitoxiantrone.

2.2. Periodontitis and Periodontal Therapy

Periodontitis is inflammation that involves periodontal tissues (gingiva,
periodontal ligament, cementum and alveolar bone) caused by bacterial plaque or
other specific dominant types of bacteria. Inflammation is caused by the presence
of toxin products from bacteria that destroy the epithelium and structure of the
periodontal tissue, causing an increase in pocket depth, loss of attachment and
alveolar bone damage (Figure 2). The bacteria that play a role in periodontitis are
estimated to be more than 400 species in the form of both gram positive and
negative bacteria which are aerobic or anaerobic, some of which are, P.gingivalis
bacteria, Actinobacillus actinomycetem comitans (Aa) and Bacteroides forsythus.

A B

7
Figure 2. Clinical and radiographic features of periodontitis A Inflammation of all
teeth and loss of attachment. B. Alveolar bone damage.

Periodontitis begins with gingival inflammation or commonly known as gingivitis

where the gingiva becomes softer, swells, shiny red, changes in the gingival
contour from the condition
mild to severe and bleeding. Poor oral hygiene conditions or lack of accurate
treatment can cause pocket deepening and migration of the unified epithelium in
the apical direction. This is usually clinically accompanied by gingival recession
and opening of the root area of the tooth. The consequence is that alveolar bone
destruction is characterized by tooth and tooth mobility that can become a date.

One histological picture of periodontitis is increased inflammatory cell

infiltration, especially macrophages and lymphocytes. The bacteria and its
products will induce cells to synthesize Interleukin-1 (IL-1) and Tumor Necrosis
Factor-α (TNF-α). Interleukin-1 and TNF-α will affect cell membranes to
synthesize cyclooxygenase-2 through arachidonic acid metabolism.

The success of periodontal treatment depends largely on the ability of the

treatment to eliminate gingival inflammation and stop the infection process.
Currently the main therapy for periodontitis is plaque control and mechanical
therapy, which is cleaning the tartar by scaling and rootplaning which aims to
reduce the accumulation of plaque and calculus. But in deep pockets, mechanical
debridement is often difficult and requires additional therapy including antibiotics
(Jaswal, 2014: 1-2).

Giving antibiotics as a systemic supplementary therapy in the treatment of

periodontitis aims to inhibit bacterial growth, reduce the severity of periodontitis
and reduce inflammatory cell infiltration. Brook mentions that additional
treatment with antibiotics is needed to support mechanical treatment, because
even though mechanical treatment, namely scaling and root planing has been able
to reduce the number of bacteria in the pocket, periodontopathogenic bacteria in

8
the dentinal tubules, gingiva and cementum are still lagging behind. Therefore
many researchers suggest the need for antibiotics in the treatment of periodontal
diseases, especially those that are progressive and destructive. Current treatment
of periodontitis usually uses a combination of groups of amoxicillin and
metronidazole.

However, the use of antibiotics that do not match the dosage or time of use
causes gastric problems, hematology, neurology, dermatology, allergies and the
occurrence of bacterial resistance (Nandini, 2012: 1-2). Giving antibiotics
systemically too have a disadvantage, namely the possibility of side effects,
including dizziness, palpitations and gastrointestinal disorders. The disorder can
be mild or severe. Even the severity of side effects can exceed the disease.
Another disadvantage is related to the balance of normal flora. Treatment of
diseases with systemic administration of antibiotics, especially those with broad
spectrum, can affect the balance of microorganisms in other places resulting in
superinfection.
Antibiotics given locally after mechanical treatment as a combination of
scaling and root smoothing can improve the effectiveness of periodontal
treatment. This facilitates antimicrobial or antibiotic drugs with polymer releasing
drugs into the periodontal pocket. This system provides benefits such as the low
dosage required, reducing systemic absorption so that minimizing the occurrence
of side effects and high concentration can be maintained on the applied side so
that the drug works more optimally.
Various forms of material have been introduced as topical therapeutic
agents in periodontal treatment including irrigation materials such as liquids and
gels (Jaswal, 2014: 2). The use of 10% doxycycline hyclate, metronidazole 25%
gel, and impegrated tetracycline fibers was shown to show the same results with
root smoothing treatment, with a decrease in pocket depth (1 mm) and increased
clinical attachment. Some studies have found that subgingival irrigation with
various types of drugs can reduce the number of subgingival pathogenic bacteria.
However, treatment with only one irrigation does not give a good and effective
response when compared to systemic antibiotics. The physical properties of

9
irrigation materials and gels that are not dense can reduce their activities and
require multiple applications, the ability and compliance of patients in applying
them. For this reason, a form of topical therapeutic agent is needed that can last
for a long time in the periodontal pocket area so that it can guarantee its
effectiveness, one of which is the periodontal chip.

2.3. Use of Chip in Periodontal Therapy

Other commercially available antimicrobials for local applications in the
periodontal pocket are chlorhexidine (PerioChip®) in the form of a 4 mm x 5 mm
plate with 350 µm thick and containing 2.5 mg chlorhexidine gluconate in the
matrix gelatin (Figure 3A). The plates packed in foil packages are clamped with
tweezers and the curved edges are pressed into the base of the periodontal pocket.
Because this material is absorbed biologically, the plate dissolves and does not
need to be removed (Figure 3 B). The chlorhexidine PerioChip® concentration in
pocket fluid is 125 µg / ml which lasts for one week.

A B
Figure 3. Periochip®. A. Shape and size. B. How to enter Periochip®. Into the
periodontal pocket.
PerioChip® is biodegradable and is indicated for 5 mm or more
periodontal pockets. In an in vitro study, Stanley et al. (1989) reported that CHX
125 μg / ml concentrations in PerioChip® inhibited 99% growth of pocket
microflora. Soskolne et al (1998) reported an average peak CHX concentration in
PerioChip® in the gingival crevicular fluid was 2007 μg / ml after two hours. For
the next 96 hours, the average CHX concentration was 1300–1900μg / ml. This
was followed by a gradual decrease in CHX concentration until the end of the
study with an average concentration greater than 125 μg / ml a day later. At the

10
end of the study there was no PerioChip® residue in one periodontal pocket. In
addition, Killoy et al (1998) research has shown that the CHX chip is most
effective when placed every three months in a pocket that is still ≥ 5 mm. Further
research by Soskolne et al. (1997) shows that PerioChip® can maintain clinically
effective CHX levels in gingival crevicular fluid (CKG) from the periodontal
pocket for more than one week with no detectable systemic absorption.
CHAPTER 3
ANALYSIS AND SYNTHESIS

Based on its structure, xanthones are classified as simple aromatic

compounds, such as dibenzofuran, dibenzopyran, and griseofulvin. The
characteristic of this group is the presence of the nucleus dibenzo-g-pyron which
shows the close relationship of xanton with flavonoids and chromomers, g-pyron
derivatives. The free xanton nucleus is a colorless needle crystal, but rarely found
in nature. While what is often found is the derivative form of the oxygens, so that
generally xanthone is isolated in the form of yellow needle crystals. Xanton and
its derivatives can be isolated from fruit peel pericarp in the form of 3-
isomangostin, alpha-mangostin, betamangostin, gamma-mangostin, garcinone A,
garcinone B, garcinone C, garcinone D, maclurin, and mangosthenol.
The melting point of xanton 173–176 ° C, so that it doesn't disappear if the
mangosteen is heated below that temperature. Hydroxyxanton compounds can
dissolve in concentrated hydrochloric acid and produce onium salts which are
easily hydrolyzed. This substance is not alkaline, but the methylation process in
the hydroxy group can increase its basicity. Demetoxy can occur by heating using
hydriodic acid, with or without the addition of glacial acetic acid or by adding
aluminum chloride in the form of a boiling benzene solution, or by adding a
chlorobenzene solution. So, the main characteristic of the xanton group is the
nature of the carbonyl group which is iner against reactants which usually react
with carbonyl groups.
In the body's metabolic processes, oxidation and reduction reactions occur,
forming oxidative free radicals with reactive oxygen. Because of its reactivity,
free radicals will oxidize substances that are beneficial to the body, causing a

11
number of damaged body tissues. For example, the skin becomes wrinkled
because it loses the elasticity of collagen and its muscles. Then spots appear as
brownish pigments or spots on the skin. It can also appear senility, parkinsonism,
or Alzheimer's because the nerve cell wall consisting of polyunsaturated fatty
acids is an easy target for free radicals.
Because it is easily oxidized, free radicals, in this case the peroxyl radical
(ROO) will oxidize xanton quickly, so that the radical peroxyl will change to R-H.
The change occurs because the oxygen molecule is reduced by garsinone B as an
xanton derivative. The reaction can inhibit free radicals of various types. Reactive
oxygen from several Examples of free radicals, such as H3C (carbon-centered), R,
R2NO (nitrogen-centered), RO, H3COO (O2-centered), or ROO, can be
eliminated by xanton garcinon B or parvixant in the oxidation process, so that
beneficial compounds can function .

In the xanton reaction with free radicals, R changes to RH, and the
reaction will make molecule A become inactive. Likewise, RO. In the presence of
xanton (Garcinon Batau parvixanton-1), position A is replaced so that the reaction
changes to SPIRIT, which can maintain substances that are beneficial to the body
to function properly to maintain health. The same thing happened to ROO, which
in the reaction process changed to ROOH.

The Moongkarndi (2004) study at Mahidol University, Thailand, showed

that pericarp of mangosteen fruit with crude methanol extract (CME) was
effective against human breast cancer SKBR3. SKBR3 is a cell that is cultured in
various concentrations, ranging from 0–50 micrograms per ml for 48 hours. CME
can inhibit the development of cancer cells in concentrations with ED (50) of 9.25
+/- 0.64 micrograms / ml. Extracts with CME provide antiproliferative effects
associated with apoptosis in breast cancer cell lines by determining changes in
morphology and oligonucleosomal DNA fragments. Changes in the structure of
DNA are caused by free radicals taking electrons from body cells, resulting in
mutant cells. If these DNA changes occur for years, cancer will appear. The

12
human body can produce, but the amount is often not enough to neutralize
incoming free radicals. Therefore humans are advised to consume xanton.

CHAPTER 4
CONCLUSION AND RECOMMENDATIONS

4.1 Conclusions
The use of mangosteen peel extract chips can eliminate periodontal pockets
because the physical properties of xanthone contained in mangosteen peel are
antibacterial, anti-inflammatory, anticancer and antioxidant so it is very well used
as a mechanical treatment support for periodontitis.

4.2 Recommendations
The innovation of the use of mangosteen peel extract chips in the treatment of
periodontal pockets provides new ideas in the development of herbal plants in the
field of dentistry, especially Periodonsia. However, research, development and /
or engineering are needed to develop practical applications of this material both in
vitro and in vivo so that accurate data is obtained regarding its effectiveness to be
equivalent to the PerioChip® materials on the market. For this reason, support
from researchers, clinicians and the government is needed in creating more high-
value products as a result of the innovations that have been carried out and
promoting sustainable industrialization and encouraging innovation in sustainable
development.

13
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