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www.elsevier.com/locate/mehy
a,b
, Jing Hu
b,*
State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, China
Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University,
No.14, 3rd Section, Ren Min Nan Road, Chengdu, Sichuan 610041, China
c
Department of Dentistry Rural Health Complex, Farooqa Sargodha,
Health Department Government of Punjab, Pakistan
b
Summary Recurrent aphthous ulcer (RAU) is the most common ulcer of oral non-keratinized mucosa, but the
treatment is always limited at present. Considering the multifactorial etiology of RAU, a novel therapeutic agent with
multi-bioactivties should be presented. Garlic has been recognized as a favorable natural medicine against a large
number of pathologic conditions. The major component of garlic is allicin, which could effectively decrease
inflammatory factors secretion, reduce the migration of neutrophils, inhibit bacterium and virus, antagonize oxidation
and regulate immunity. By these bioactivities of anti-inflammation, anti-microbial activity, anti-oxidation and
immunomodulation, the allicin may be an effective therapeutic candidate to control the pain, promote ulcer healing
and prevent the recurrence of RAU.
c 2008 Elsevier Ltd. All rights reserved.
0306-9877/$ - see front matter c 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2008.07.028
898
major component of natural garlic extracts, could
treat RAU effectively with their multiple bioactivities, such as anti-inflammatory, anti-microbial,
anti-oxidative and immunomodulatory properties.
For many centuries, garlic has been recognized
as a valuable folk medicine with a favorable effect
against a large number of pathologic conditions
[4,5]. Garlic became an object of interest due to
its potential to confer a vast spectrum of health
beneficial effects including: anti-inflammatory,
anti-microbial, anti-fungal, anti-parasitic, antihypertensive and anti-cancer activities [4,5]. Allicin, which is the main biologically active compound
derived from garlic [46], can undergo thiol-disulphide exchange reactions and react with free thiol
groups [7]. The reactivity with enzymes, the radical-trapping properties and membrane permeability, are regarded as the basis of their efficient
biological activities [7,8].
There are several reasons lead to formulation of
the hypothesis that the allicin could be a potential
and effective therapeutic candidate for treatment
of RAU.
First, allicin may exert as an effective antiinflammation agent to control the symptoms of
RAU. Previous studies confirmed the exorbitant
inflammation contribute to the initiation of RAU
[2,3]. The anti-inflammatory agents were regarded
as the first-line agents to control the symptoms of
RAU [2]. Excessive inflammatory cells and factors
participate in the formation of ulcers and stimulate
the sensory nerve endings. Several inflammatory
factors play prominent roles in RAU and are studied
extensively, such as tumor necrosis factor-a (TNFa), and interleukin (IL) [3]. Allicin could decrease
the TNF-a protein and mRNA level in a dose-dependent manner [9,10] and suppress both the spontaneous and TNF-a-stimulated secretion of the
cytokines, such as IL-1, IL-6, IL-8, and leukotriene
by down regulating mRNA levels and inhibiting the
activation of the nuclear factor-jB (NF-jB) pathway [9,11,12]. It could also stimulate the production of IL-10, which exerts the main negative
regulatory feedback on Th1 cytokine production,
by monocytes/macrophages. IL-10 suppresses the
production of TNF-a and IL-2, IL-6, IL-12 by T cells
[13], and down-regulates intercellular adhesion
molecule (ICAM) which plays an positive role in
the regulation of cellular inflammatory responses
[14]. Moreover, allicin still can induce up-regulation of glutathione (GSH) which has a crucial role
in vivo in down-regulation of the levels of proinflammatory cytokines, thereby inhibiting the progression of the disease [15]. According to these
findings, allicin could decrease inflammatory cytokines expression, increase anti-inflammatory cyto-
Jiang et al.
kine expression, hence help decrease exorbitant
inflammatory processes, which may have a therapeutic effect for RAU.
Second, garlic extracts have been regarded as
extensive anti-microbial agents used in ancient
times against bacterium, virus and fungus [4,5].
Allicin has been proven to inhibit the growth of
gram-positive, gram-negative, and acid-fast bacterium, including multidrug-resistant bacterium [16].
With lower concentration, it could effectively reduce the total oral bacterium [17]. Bacterium and
virus both contribute to the pathogenesis of RAU
[3]. It was proven that the heat shock protein
(HSP) 65-derived peptide from special oral bacterium was the homologous peptide of HSP60 in the
non-keratinized epithelia, and could stimulate
numerous Langerhans cells to activate abnormal
cross-reacting immune response, which contributed to the initiation of RAU [18]. Allicin is also
effective in prevention and treatment of gastric ulcers [19] by the inhibition of Helicobacter pylori
(HP) infections. HP also plays an important role in
RAU by inducing lymphocyte-derived cytokines
which promote the local accumulation of neutrophils and release of proteolytic enzymes and oxygen radicals [20]. Moreover, allicin has been
shown in in vitro studies to have antiviral activity
against Cytomegalovirus, Herpes simplex virus,
and Vesicular stomatitis virus [21] that may act as
causative pathogens of RAU by activating excessive
immune response [22]. From these findings, allicin
may eliminate the possible microbial pathogens of
RAU, so facilitate to reduce the recurrence of RAU.
Third, allicin still possess other bioactivities and
possibly participate in the treatment of RAU. It
contains a wide range of antioxidative ability
[23,24], which could significantly decrease the lipid
peroxidation and scavenge hydroxide radicals, lower plasma and erythrocyte malondialdehyde (MDA)
levels, recover GSH depletion, and increase the
cellular antioxidant enzymes. So it may rebalance
the impaired enzymatic and nonenzymatic antioxidant defence systems in patients with RAU [25].
Currently, available data suggest that allicin may
be a promising candidate as a biological immune
response modifier, being able to stimulate necessary functions and suppress unnecessary functions,
what could normalize the immune disfunction in
RAU [11,26].
The above evidence suggests that allicin may
have a useful therapeutic effect in RAU through
their anti-inflammatory, anti-microbial, anti-oxidative and immunomodulatory effects. For the
treatment of RAU, topical medication has played
a crucial role in reducing ulcer pain and accelerating ulcer healing [27]. The local usage of allicin
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
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