ArticlePDF AvailableLiterature Review

Nigella sativa and its active constituent thymoquinone in oral health

Authors:

Abstract

In this review, we summarized published reports that investigated the role of Nigella sativa (NS) and its active constituent, thymoquinone (TQ) in oral health and disease management. The literature studies were preliminary and scanty, but the results revealed that black seed plants have a potential therapeutic effect for oral and dental diseases. Such results are encouraging for the incorporation of these plants in dental therapeutics and hygiene products. However, further detailed preclinical and clinical studies at the cellular and molecular levels are required to investigate the mechanisms of action of NS and its constituents, particularly TQ. © 2016, Saudi Arabian Armed Forces Hospital. All rights reserved.
Nigella sativa and its active constituent thymoquinone in
oral health
Safia A. AlAttas, MS, FAAOM, Fat’heya M. Zahran, MS, PhD, Shereen A. Turkistany, BD, MS.
235
ABSTRACT
—Ëœ w XIIŠ w²« …—uAM*« d¹—UI²« WÝ«—b« Ác¼ w hK½
ÃöŽË W× w ÊuM¹uu1U¦« UN jAM« ÊuJ*«Ë Wd³« W³Š
UN²¹«bÐ w ÀU×Ð_« Ê√ XMOÐ wÐœ_« `*« ZzU²½ ÆrH« ÷d√
¡«œu« W³(« UðU³½ Ê√ ZzU²M« dNþ√ sJË ¨œbF« …œËb×Ë
ZzU²M« Ác¼ ÆÊUMÝ_«Ë rH« ÷«d_ WKL²× WOłöŽ «dOŁQð UN
ÊUMÝ_«Ë rH« ÷«d√ …«Ë«b w UðU³M« Ác¼ ÃUœù WF−A
d¦√ UÝ«—œ qLF WłUŠ „UM¼ ¨p– lË ÆWUEM« U−²MË
WO¾¹e'«Ë W¹uK)« U¹u²*« vKŽ W¹d¹d« q³UË W¹d¹dÝ öOBHð
WUšË ¨UNðU½uJË Wd³« W³Š qLŽ UO¬ w oOIײK
ÆÊuM¹uu1U¦«
In this review, we summarized published reports
that investigated the role of Nigella sativa (NS) and
its active constituent, thymoquinone (TQ) in oral
health and disease management. e literature studies
were preliminary and scanty, but the results revealed
that black seed plants have a potential therapeutic
effect for oral and dental diseases. Such results are
encouraging for the incorporation of these plants in
dental therapeutics and hygiene products. However,
further detailed preclinical and clinical studies at the
cellular and molecular levels are required to investigate
the mechanisms of action of NS and its constituents,
particularly TQ.
Saudi Med J 2016; Vol. 37 (3): 235-244
doi: 10.15537/smj.2016.3.13006
From the Department of Oral Diagnostic Sciences (Al-Attas, Zahran),
Faculty of Dentistry, the Centre of Innovation in Personalized
Medicine (Turkistany), King Abdulaziz University, Jeddah,
Kingdom of Saudi Arabia.
Address correspondence and reprint request to: Professor Safia A.
AlAttas, Department of Oral Diagnostic Sciences, Faculty of Dentistry,
King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
E-mail: salattass@kau.edu.sa
Review Articles
www.smj.org.sa Saudi Med J 2016; Vol. 37 (3)
Currently there is a worldwide growing interest
on the use of medicinal herbs or plants in the
treatment of various diseases due to their promising
results and fewer side effects.1 According to the World
Health Organization (WHO), 60-80% of the world’s
population particularly in developing countries,
depends on herbal remedies or traditional medicine
for their primary health care and treatment. Moreover,
the WHO has encouraged developing countries to use
their medicinal plants as a resource to generate effective
health care programs.2,3 One of the top ranked evidence-
based herbal medicines, which has been described as the
“miracle herb of the century is Nigella sativa (NS).3,4
Nigella sativa is an annual flowering plant in the family
Ranunculaceae (Table 1) also called black cumin, black
seed, or Habbatul Barakah is native to the south and
southwest Asia, and is cultivated in several countries in
the Mediterranean region, South Europe, Syria, Turkey,
and Saudi Arabia.5,6 Historically, ancient Egyptian and
Greek physicians used NS seeds in the management
of several diseases, such as headache and toothache,
congestion of the nose, intestinal worms, promotion of
menstruation, and production of milk.7,8 e black seed
has a spiritual and religious impact in many Muslim
populations, as the prophet Mohammad said “use the
black seed regularly because it is a cure for every disease,
except death,’which could explain its extensive use by
millions of Muslims all over the world.9
Researchers have attributed the health promoting
benefits of the black seed to its active components and
high nutritional content.3 e seeds are composed of
28-36% fixed oils, proteins, alkaloids and saponins,
and 0.4-2.5% essential oils. Many pharmacologically
Disclosure. Authors have no conflict of interest and the
work was not supported or funded by any drug company.
is work was funded by the Scientific Research Council
(Project Code 2-165-35-RG), King Abdulaziz University,
Jeddah, Kingdom of Saudi Arabia.
OPEN ACCESS
236
N. sativa and thymoquinone in oral health ... Al-Attas et al
Saudi Med J 2016; Vol. 37 (3) www.smj.org.sa
active compounds have been isolated from black
seeds, but the most reported active constituents are
thymoquinone (TQ), dithymoquinone, thymol, and
thymohydroquinone. Several nutritional components
are found in the seeds, such as carbohydrates, fats,
essential amino acids and vitamins. e seeds are
also considered to be a source of potassium, calcium,
and iron.4,8 Several authors have extensively reviewed
NS and its active component, TQ, and found them
to have many pharmacological properties, such as:
antimicrobial (antibacterial, anthelmintic, antifungal,
and antiviral); anti-inflammatory; analgesic; histamine
release inhibitor; antihypertensive; hypoglycemic;
anticarcinogenic; antioxidant; and hepatoprotective
among others.3,5,6 Oral health and the integrity of the
oral cavity are crucial to the general health of human
beings. Many oral diseases are preventable, and for
many years, the use of plants, oral health care, and
therapeutic practices have been closely related.10-12 A
literature review revealed that studies relating NS to oral
health are scant, and as of this date, no published report
summarizes their findings. e aim of this report is to
summarize the published studies on the role of NS and
its active component, TQ, in oral health.
PubMed and Google Scholar were used for
data search, and up-to-date papers in English were
selected using the following key words: Nigella sativa,
thymoquinone, oral health, dental health, periodontal
diseases, caries, pulp treatment, oral cancer, and oral
squamous carcinoma. e collected data are presented
in subheadings related to oral health issues.
Dental caries. Dental caries or tooth decay is
a progressive, irreversible microbial disease that is
characterized by bacterial fermentation of carbohydrates
resulting in acid production, and the subsequent
destruction of the hard tissues of the tooth. Streptococcus
mutans (S. mutans) and Streptococcus sobrinus are
the major suspected pathogens in the initiation and
progression of dental caries.13-15 According to a WHO
report, dental caries affect nearly all adults at some
point in their life.16 It remains a health problem and
a challenging disease inspite of the worldwide public
health strategies that have focused on preventive
methods, such as water fluoridation, and application of
topical fluorides.13 Recently, some authors investigated
the preventive effect of natural products on dental
caries.17,18 Although many authors believed that NS
and TQ might have a role in caries prevention because
of their antibacterial properties, there have been few
published studies on this topic. Only one study13 was
found with a rat experimental model, its aim was to
investigate the effect of NS on caries initiation through
the inhibition of microbiome formation. In that
study,13 the animals were challenged with S. mutans
and fed a diet rich of sucrose. e results showed that
the rats’ treatment with 10 mg of TQ per body weight
(in kg) in oral gel or drinking water statistically reduced
the caries score (p=0.02) and plaque index (p=0.01)
in comparison with the control groups. e authors
attributed the decrease in dental caries to the microbial
biofilm inhibition properties of TQ.13
Streptococcus mutans remain the major pathogen in
dental caries. Its pathogenicity is due to the production
of extracellular polysaccharides and its ability to bind
dental tissues through a biofilm and subsequent plaque
formation.15,19 e microbiome is composed of salivary
glycoproteins, bacteria (cocci, bacilli, and filamentous
forms) and their metabolic end products arranged in
a matrix of extracellular material. Dental microbiome
accumulates on and adheres to the teeth, restorations
and prosthetic appliances in the mouth, and plays an
important role in oral and dental diseases.20 Natural
products have recently been investigated as promising
alternatives to synthetic antimicrobial drugs, including
herbal products, such as NS and TQ.1,12,13,18,21-23
Harzallah et al18 carried out a research to assess the
anticariogenic activity of the Tunisian NS essential
oil and its TQ. ey used the method of broth
microdilution to evaluate the minimum inhibitory
concentration (MIC) of the NS essential oil and its TQ
for oral cariogenic pathogens. Surprisingly, they found
that 2.43 mg/disc essential oil contained only 3.35 μg/
ml TQ, and showed more antimicrobial activity than the
pure TQ compound (150 μg/disc). e latter was active
against all of the studied strains, especially S. mutans,
which showed inhibition zones of 24.5 ± 0.71 mm, and
Streptococcus mitis (S. mitis) with 22 ± 1.41 mm. ey
explained the antibacterial effect of NS essential oil,
even with a minimal amount of TQ, as being caused by
its other more potent bactericidal components, such as
p-cymene, limonene, and apinene.18 e black seed oil
extracts were not only found to have a bactericidal effect
Table 1 - Scientific classification of Nigella sativa.8
Kingdom Plantae
Subkingdom Tracheobionata, that is, vascular plant
Supervision Spermatophyte
Order Ranunculales
Family Ranunculaceae-butter cup family
Genera Nigella
Species N. sativa
237
www.smj.org.sa Saudi Med J 2016; Vol. 37 (3)
N. sativa and thymoquinone in oral health ... Al-Attas et al
against S. mutans but also to have an effect on inhibiting
the adherence of S. mutans to the surface of the teeth.
Abd-Awn et al1 conducted a research using an agar
diffusion test followed by a minimum bactericidal
concentration (MBC) determination to test the NS oil
extract’s sensitivity to S. mutans and its ability to inhibit
bacterial adherence to the dental plaque compared with
chlorhexidine gluconate. e results showed that the
black seed oil extract has 10% MBC against S. mutans.1
However, the authors recommended that further
studies with different types of extracts (including
those from different regions) be evaluated for the
antibacterial activity of the black seed. In addition, they
recommended an analysis of the extracts for their active
ingredients, which are responsible for their antibacterial
activity. ey also cited the urgent need for finding a
standard method for extract preparation.1 e last point
was found to be valid, as Mohammed24 evaluated 2
different extracts of NS against 2 cariogenic bacteria,
S. mutans and S. mitis. e results demonstrated that
the inhibition zone for the ethanol extract was 12.7 mm
against S. mutans, and 10.4 mm against S. mitis, while
the inhibition zone for the ether extract was 6.3 mm
against S. mutans, and 5.1 mm against S. mitis. is
means that methanol extraction had a stronger effect
against the bacteria than did the ether extract.24
Periodontal and gingival diseases. Periodontitis is
microbiome-related dental inflammation caused by
Gram negative bacteria, resulting in connective tissue
destruction beyond the gingiva around the teeth.25,26
Almost 200 systemic diseases are connected to oral
health according to the American Dental Association.27
Periodontitis alone was found to have an established
association with several systemic conditions, such
as diabetes mellitus, cardiovascular and pulmonary
diseases, low birth weight, and other conditions.28,29 As
for dental caries, proper oral hygiene and microbiome
control are also very important strategies for periodontal
disease prevention. However, most of the population
does not perform proper mechanical microbiome
control due to lack of motivation or dexterity.30 e
regimen of periodontal treatment often includes the use
of antibacterial agents, which can reach diseased sites
systemically, or topically. A recent systematic review
showed that mouthwashes containing chlorhexidine
present high antiplaque (mean reduction of 40%),
and antigingivitis efficacy (mean reduction of 28%),
however, their adverse effects (such as, teeth and soft
tissue staining) limit their use.31 Many herbal products
have been used as alternatives to these synthetic drugs.20
Because of the antibacterial, anti-inflammatory, and
antioxidative properties of NS and TQ, the authors
believe that these products could have a role in
periodontal disease.32 In the rat model proposed by
Al-Wafi et al,13 besides the anti-caries assessment, an
evaluation of the potential preventive role of TQ on
gingival inflammation was conducted. e results
revealed that rats treated with TQ in drinking water or
an oral gel had statistically significant lower periodontal
indices and subgingival bacterial counts in comparison
with both the negative and positive control groups.
Additionally, their mandibular tissues, which were taken
for histological examination to determine the degree of
inflammation, demonstrated no signs of inflammation
compared with the controls. Another in vivo study,32
also in a rat periodontitis model, investigated the
preventive role of TQ in periodontal inflammation
initiation and progression. In that study,32 the gingival
margins of the rats’ molars were ligated with a 4/0 silk
suture to induce periodontitis. e experiment included
24 rats that were randomly and equally distributed into
3 groups; nonligated (NL), ligature only (LO), and
ligature plus daily treatment (TQ at 10 mg/kg). On day
11, the animals were sacrificed and in each group the
alveolar bone levels of molars were clinically measured
and examined histopathologically. e results revealed
that there were statistically significant higher bone
losses in the LO group in comparison with the NL and
the TQ groups. e same was reported regarding the
ratio of inflammatory cell infiltration to osteoclasts.
However, the reverse was true regarding the osteoblasts,
which showed significant lower activity in the LO
group than in the NL and TQ groups. us, it was
concluded that the oral administration of TQ helped
in periodontal disease prevention as it diminished
alveolar bone resorption.32 Additionally, a clinical
randomized single-blind split-mouth trial26 was carried
out to evaluate the effectiveness of a TQ-impregnated
periodontal chip in chronic periodontitis. e study
included the periodontal pockets of 12 male patients
with chronic periodontitis. ey were distributed
into 3 groups: control (no treatment), plain chitosan
chips, and TQ chips.26 Interestingly, the results showed
significant gains in the clinical attachments in the TQ
groups compared with the other groups. Al-Bayaty et
al26 advised the use of TQ chips in chronic periodontitis
patients as an adjunctive treatment during the scaling
and root planing, or for maintenance visits.
Pulpal diseases. Intracanal antisepsis is considered
to be one of the fundamental steps in root canal
therapy. Antimicrobial irrigating solutions and other
locally used disinfecting agents and medicaments play
238
N. sativa and thymoquinone in oral health ... Al-Attas et al
Saudi Med J 2016; Vol. 37 (3) www.smj.org.sa
a key role in the eradication of microbes.33 An ideal
root canal irrigant should have high efficacy against
microorganisms in biofilms while being systemically
nontoxic and noncaustic to periodontal tissues.34
Although current irrigation regimens using sodium
hypochlorite (NaOCl) exhibit excellent antimicrobial
activity, caustic, and toxic effects to vital tissues are
often noted. erefore, there is a need for agents
that are both antibacterial and that exert minimal
tissue irritation. Plant-derived products represent a
rich source of antimicrobial compounds, and some
have been incorporated into oral hygiene products.
However, their application in endodontics is less well
documented.35 Only 2 studies33,36 have been found to
evaluate the possible use of NS or TQ in endodontics.
One study33 evaluated the antibacterial action of NS
with 5 different concentrations of aluminum potassium
sulfate (alum), Salvadora persica (Siwak), and a
combination of all these on root canal bacteria isolated
from 20 patients. e authors33 found that all 3 tested
herbs had bactericidal effects, and that the NS aqueous
extract (100% concentration) showed maximum
inhibition zones of 26 mm in diameter for Enterobacter
cloacae, 22 mm in diameter for Streptococcus oralis, 21
mm in diameter for Streptococcus anginosus, 20 mm in
diameter for Staphylococcus epidermides, and 16 mm in
diameter for Enterobacter cloacae, Streptococcus oralis,
Streptococcus anginosus, Staphylococcus epidermides and
Enterococcus durans. Another study36 searched for a new
capping medicament in pediatric dentistry to replace
formocresol because of its reported side effects. e
study compared the histopathological pulp response
to NS oil and formocresol (FC) in dogs. e results
showed that NS specimens histologically revealed mild
to moderate vasodilatation with few inflammatory cells
and a continuous odontoblastic layer. On the other
hand, FC specimens showed advanced inflammation
with severe vasodilatation and inflammatory cell
infiltration and degeneration. us, application of NS
maintained the vitality of the pulp, which makes it a
good pulpotomy agent in clinical practice.36
Oral ulcerations, oral mucositis and wound healing.
Oral ulcerations are common painful lesions that are
related to various conditions ranging from minor
local trauma to significant systemic conditions, such
as hematological, gastroenterological, dermatological,
and immunological diseases and malignancies.37,38
Topical NS oil was found to have a good therapeutic
effect on the healing of chemically induced oral ulcers.
Al-Douri and Al-Kazaz39 carried out an experiment on
12 rabbits. e authors created the ulcers with 0.3 ml
of 1% formalin injections in the cheek mucosa of the
rabbits followed by topical application of NS twice a
day for 3 days. e animals were sacrificed on the
fifth day, and their cheek mucosae were histologically
examined. e results showed a significant healing
process enhancement with NS treatment, and a marked
anti-inflammatory activity and differences in the rate of
epithelization between the NS and control groups. e
authors justified the results by asserting that the NS oil
accelerated the healing of ulcers, because it inhibited the
growth of pathogenic organisms at the site of the ulcers,
which could retard the healing process. Moreover, the
TQ flavonoids and the other components in the NS oil
(vitamins and minerals) make it an excellent promoter
of ulcer healing.39
Oral mucositis due to chemotherapy and radiotherapy
represents a problematic side effect in cancer treatment.
A study in a rat model evaluated the capacity of NS
to decrease the severity of chemotherapy-induced
mucositis.40 In that study,40 25 male albino rats were
divided randomly into 3 groups: control, untreated, and
treated. An intraperitoneal injection of 5 fluorouracil
(5FU) was used to induce mucositis in rats, and their
cheek pouches on the right side were scratched with a
wire brush to induce mucositis. Rats in the untreated
group received oral physiologic saline, and those in the
treated group were gavaged daily with 1 ml of NS seed
extract (400 mg/kg). Rats were sacrificed on day 14,
and the cheek pouch areas were excised and prepared for
histological and immunohistochemical analysis using
Bcl2 and PCNA immune labelling. e results showed
that in comparison with controls and 5FU untreated
rats, NS decreased the histologically observed damage
of the cheek mucosa in the mucositis model. e results
suggested NS as a promising prophylactic adjunct to
conventional chemotherapy for reducing the severity of
oral mucositis.40
Despite reports on the accelerated healing process
and scarless wounds in the oral cavity, in contrast to
wounds on the skin, healing oral wounds remains a
challenge due to the continuous saliva flow, and the
presence of microorganisms that tend to interrupt and
slow down the healing process. An in vitro study41
investigated the wound healing promoting properties of
4 aqueous extracts of Asian traditional medicinal plants:
NS, Melastoma malabathricum, Pluchea indica, and
Piper sarmentosum. e in vitro scratch assay was used
to assess the effect on wound healing activity, while the
extracts’ effect on collagen synthesis by human gingival
fibroblasts (HGF) was determined by hydroxyproline
levels. e NS extract (NSE) showed a significant
239
www.smj.org.sa Saudi Med J 2016; Vol. 37 (3)
N. sativa and thymoquinone in oral health ... Al-Attas et al
enhancement of HGF proliferation compared with
other extracts and accelerated wound closure despite its
lack of significant effect on collagen synthesis.41
Bone healing/socket and implants. Recently, it has
been reported that black seed induced bone healing
in extracted teeth sockets and manifested faster bone
trabeculae formation.42 is was an animal study,42
in which the therapeutic effect of both powder and
oil forms of NS on socket healing were investigated.
e sample included 24 male New Zealand rabbits.
e researchers extracted the rabbits’ incisors, filled
the extraction sites with NS powder or oil material,
and compared the healing with the other side of the
mouth (control group).42 e extraction sites were
examined radiographically and histologically after one,
and 6 weeks. e results showed an early detection of
osteoid formation at the first week and bone trabeculae
formation at the 6th week in sockets treated with NS
(powder and oil). However, in the histological study,
it was found that at the extraction sites, NS powder
was more effective than the NS oil in terms of bone
formation.42 ey attributed this result to the complete
absorption of the powder compared with the oil, which
was applied with a piece of cotton for only 5 minutes
and then removed.42
Natural plants were proposed as a coating
agent because the biological molecules improve
osseointegration in dental implants.43 However,
the literature concerning NS and bone healing is
contradictory. A disappointing study was conducted
by El-Sweify et al44 to identify the effect of calcium
hydroxide powder mixed with NS oil compared with
bioglass on the healing of mandibular bone defects in
rats. e experiment included 40 albino rats that were
subjected to surgical procedures to induce a mandibular
surgical defect and were distributed into 4 groups.
Group I was the control group, where the bony defects
were left empty; Group II had bony defects that were
filled with calcium hydroxide powder mixed with saline;
Group III had bony defects that were filled with calcium
hydroxide mixed with NS oil; and Group IV had bony
defects that were filled with ready made bioactive glass
particulates. After 3 weeks, one half of the animals were
sacrificed, while the other half was sacrificed after 6
weeks. e results revealed that all of the used materials
were biocompatible with the animal model, but the
bioglass seemed to have the highest osteoconductive
and osteostimulatory effects among the materials used.
ere was no bone formation in Groups I, II, and III
after 3 and 6 weeks. Group IV after 3 weeks showed
only minute amounts of osteoid tissues; however, after
6 weeks, more fibrous tissues were seen, and the borders
of the defects were of normal thickness, and were
smooth and lined by a well-defined osteoblastic layer.44
On the other hand, an in vivo study43 was conducted
to investigate the black seed oil extract’s effect on the
bone implant interface’s mechanical and histological
properties. In the experiment, 12 New Zealand rabbits
received 4 screw-shaped (84 CpTi) implants in the tibiae
bone. e implants were divided into 2 groups; coated,
and uncoated with black seed oil extract. e results
showed that over different periods of time, the coated
implants had significantly better torque resistance than
the uncoated implants, and histologically revealed early
osseointegration with an osteophilic surface, as well as
no adverse tissue reaction.43
Microbial diseases. A) Antibacterial activity. ere
have been many studies that have investigated the
antimicrobial effect of NS, but they are not in the scope
of this review, although a few are mentioned. Currently,
there is an urgent need for new antibacterial drugs to
overcome the emergence of oral bacterial resistance.
Interestingly, an in vitro study22 was carried out to assess
the TQ’s inhibitory and resistance-modifying ability
against a panel of pathogenic bacteria, including oral
isolates. e results revealed that TQ demonstrated a
selective antimicrobial property; it was effective against
Gram positive bacteria, but Gram negative bacteria were
resistant to it.22 However, there was a 4-fold potential
effect of tetracycline and benzalkonium chloride (BC)
against the tested pathogens. us, TQ can be used in
multidrug resistant infections.22
More recently, a laboratory study45 was conducted
to compare the antibacterial effect of NS oil extract
with nanosilver and amoxicillin using the disk
diffusion method on oral S. mutans and S. sanguis.
e results showed that the NS oil at a concentration
of 330 mg/mL, demonstrated an inhibitory zone of
22 mm for S. mutans, and 9.75 mm for S. sanguis.
Meanwhile, the bacterial inhibitory zone of each of
the nanosilver concentrations at 3500 ppm and the
standard amoxicillin disc (25 μg) was 33.5-19.75 mm
for S. mutans and 11-21.75 mm for S. sanguis.45 us,
nanosilver had the highest antibacterial activity against
both bacterial strains, while NS and amoxicillin had a
similar effect on S. mutans and NS was more effective
than amoxicillin against S. sanguis.45
B) Antifungal activity. Oral candidiasis is a common
infection in the oral cavity caused by fungi, mostly
Candida albicans.46 Amphotericin B and triazoles, such
as fluconazole and itraconazole are the most common
antifungal agents that have been used systemically, or
240
N. sativa and thymoquinone in oral health ... Al-Attas et al
Saudi Med J 2016; Vol. 37 (3) www.smj.org.sa
topically for fungal infections. Unfortunately, with a
prolonged course of therapy, fungal resistance erupts
as a challenge. Again, the medicinal plants have been
attractive to scientists as possible alternative fungal
treatments.47-50
In Hail province, a study50 assessed the in vitro
inhibitory activity of ethanol extracts from 6 plants
against oral candidal isolates. e latter were 65
Candida isolates collected from 175 patients attending
private dental clinics. e experimental plants, which
were purchased from local Saudi markets, included the
following: Zingiber officinale (ginger); Cinnamomum
(cinnamon); NS (black cumin); Syzygium aromaticum
(clove); Piper nigrum (black pepper), and chamomile.
It has been found that the highest inhibitory effects
were reached with a 100 μg/ml concentration of
cinnamon (34.6 mm) and clove (31.5 mm), while the
same concentration of black cumin and chamomile
recorded the smallest inhibition zone.50 However, the
mean values of the inhibition zone of both the black
cumin and chamomile were not significantly different
from that of Amphotericin B.5 Another study,51 claimed
by the authors to be the first of its kind investigated
the in vitro antifungal properties of Amphotericin B,
ketoconazole, and TQ against Candida albicans (yeasts
and biofilm) in their nanoparticle forms in comparison
with their conventional forms. e results showed that
the nanosized drugs’ fo-rmulation increased the drug’s
efficacy 24 times against Candida albicans in both yeast
and biofilm forms. us, this finding represents a major
innovation in the medical field, as biofilm growth is
more protected from host defenses and has enhanced
resistance to antimicrobial agents.51
Oral cancer. Oral cancer is considered to be a
multistep disease of accumulated genetic and epigenetic
alterations in epithelial cells, which generally precedes
histological changes. ese changes accumulate
throughout malignant transformation from benign
to precancer lesions to the invasive cancer state.52,53
Oral cancer is ranked as the sixth most frequent
cancer worldwide. Unfortunately, the 5-year survival
for oral cancer has remained at 50% for a long time.
is occurrence is due to several factors, such as late
diagnosis, disease relapse, resistance to chemotherapy,
and metastasis.54,55 Premalignant lesions could be
subclinical conditions with normal mucosa or clinically
obvious lesions, such as leukoplakia, erythroplakia, and
submucous fibrosis. Studies showed that premalignant
lesions are reversible conditions, as epithelial tissues
retain normal mucosal morphology. is is true if
carcinogenic insults related to an unhealthy lifestyle
habits (such as, alcohol consumption and tobacco
smoking) were adjusted. However, changing unhealthy
habits might be hard for some, or undesirable for
others. Instead, using pharmacological or natural
products to prevent the progression of premalignant to
cancerous lesions is a very attractive approach known
as chemoprevention.54,56-58 Studies revealed that TQ
restrains proliferation and promotes apoptosis in human
cancer cell lines.59-61
In addition, TQ can be used as a chemosensitizing
agent with drugs, or can be used with other
chemotherapy drugs to achieve a synergistic effect. An
example of this co-treatment is the combination of TQ
and cisplatin, which was found to have a synergistic
effect in preventing the proliferation and invasion of
human lung cancer.62 Here, we focus on the effect of
TQ in oral cancer treatment and prevention. Although
only a few studies have been performed on the effect
of TQ on oral cancer, it is still promising.60,63,64 A
study by Chu et al60 revealed that the treatment of
human oral cancer with TQ induces cell death by the
2 distinct mechanisms of apoptosis and autophagy.
Apoptosis is programmed cell death. It is regulated by
either the receptor-mediated death pathway, or by the
mitochondrial pathway. Apoptosis causes changes to the
cell that are characterized by cell shrinkage, bulge of the
membrane, breakage of DNA, and caspase activation.65
Autophagy is an important physiological process that
sustains cellular homeostasis under stress conditions.
In cancer therapy studies, autophagy-inducing agents
are used to stimulate nonapoptotic cell death.66
Experiments were performed in vitro and in vivo,
which strongly supported the TQ’s antitumor activity.
In vitro, treating SASVO3 oral cancer cells with TQ
inhibited the growth of cells. ese cells were arrested
at the sub G1 phase (apoptotic cell population). Protein
expression by western blots of Bcl2 (an inhibitor of
apoptosis) and Bid were decreased in a dose-dependent
fashion.
On the contrary, the protein expression of Bax (a
promoter of apoptosis) and cleaved caspase 9 were also
increased in a dose-dependent fashion. To verify the
activation of apoptosis through caspase 9, the authors
incubated SASVO3 cells with TQ and the caspase
9 inhibitor. Staining with annexinV/PI revealed a
decrease in the TQ-induced apoptotic population
after treatment with the inhibitors. Taken together,
TQ induced apoptosis through the initiation of
caspase 9. Autophagy-related proteins Beclim 1, class
III PI3K complex, Rubicon, and Atg family proteins
were expressed in SASVO3 cells treated with TQ.
Additionally, as a protein indicator of autophagy,
LC3II increased after TQ treatment and TQ induced
autophagy. In vivo, nude mice were injected with
241
www.smj.org.sa Saudi Med J 2016; Vol. 37 (3)
N. sativa and thymoquinone in oral health ... Al-Attas et al
luciferase expressing SASVO3 cells. Mice were
treated with either TQ or olive oil (control). e TQ
treatment reduced tumor weight by 3.4-fold by the
20th day. Protein expression of the TQ-treated tumor
showed high levels of Bax and LC3II compared with
the control animals. ese results supported the in
vitro results, where TQ treatment prompted apoptosis
and autophagy in vivo. is study verified the need
of multiple target therapy as an effective approach in
anticancer treatment.60 Abdelfadil et al64 carried out a
study on the treatment of oral cancer cells with TQ.
eir results showed that TQ induced apoptosis. e
mouse cell line used in that study represents chemically
induced oral squamous cell carcinoma (T28). Treating
T28 with TQ induced apoptosis through the blocking
of the p38β MAPK pathway and increased expression of
proapoptotic proteins Bid and Bad with the activation
of p53. Apoptosis in T28 cells occurred through caspase
3 cleavage. e difference in the apoptosis pathway
between this study and the previous one is probably due
to the use of different cell lines (human versus animal).
Interestingly, TQ treatment induced downregulation of
COX2, which in turn, decreases cell survival. Abdelfadil
et al64 stated that TQ has a promising potential in
anticancer therapy by promoting apoptosis and reducing
cell survival. e TQ not only can be used as a treatment
for cancer but also as a chemopreventive. It prevents
premalignant lesions to progress to cancer. Many studies
have illustrated this concept regarding TQ in different
cancer types.67,68 Only one oral cancer prevention study
through the use of TQ has been published.63 ey used
7,12 dimethyl benz (a) anthracene (DMBA) in an
induced hamster buccal pouch carcinogenesis model
to study TQ chemoprevention. e DMBA is known
to induce multistep carcinogenesis. It starts with a
sequence of hyperplasia, dysplasia and carcinoma,
which is very similar to the development of oral cancer.
For animals treated with TQ, the incidence of oral
neoplasm and cytokeratin expression was significantly
prevented.63 e NSE can be used in combination
with chemotherapeutics, such as cisplatin, to enhance
the anticancer activity of the drug and as a protective
agent for organs from its cytotoxic effect. We verified
the protective effect of NSE in a DMBA-induced
hamster buccal pouch carcinogenesis model treated
with cisplatin.69 e NSE protected the hamster kidney
from nephrotoxic effects. Kidney function tests showed
lower values in hamsters treated with TQ and cisplatin
than hamsters treated with cisplatin alone. In addition,
as found in this study, liver functions were better in the
NSE-treated groups. In summary, NSE, and particularly
TQ are promising products in the prevention and
treatment of oral cancer.
Conclusion and recommendations. e few last
decades have shown a rise in using herbal medicine
investigations to replace conventional treatments for
Table 2 - e effects of Nigella sativa (NS) extracts and thymoquinone (TQ) in dental caries and periodontal diseases.
Disease type Experimental model Treatment effects Reference
Dental caries (cariogenic bacteria)
In vivo Rats were challenged with Streptococcus mutans (S.
mutans) and fed a diet rich in sucrose
Lowered the caries score and plaque index 13
In vitro e antibacterial activity of NS essential oil and TQ
were screened against 30 human cariogenic strains using
the agar disk diffusion assay and minimum inhibitory
concentration (MIC) determination
NS essential oil showed more antimicrobial activity than
the pure TQ, NS essential oil has strong activity against
Streptococcus mitis (S. mitis), S. mutans, (MIC 2.13 mg/
ml),TQ showed a most important antibacterial activity
against S. constellatus (MIC 4 μg/ml)
18
In vitro Inhibition of teeth adherence was tested, as well as the
antibacterial activity using agar diffusion test followed by
minimum bactericidal concentration (MBC)
e black seed oil was effective in inhibiting the
adherence of S. mutans to the tooth surface at 10%
concentration. e black seed oil ethanolic extract has
10% MBC against S. mutans
1
In vitro e antibacterial activity was tested with the microwell
dilution method (the Kirby-Bauer method)
e results demonstrated the methanolic extract had
a higher zone of inhibition than either extract of NS
against S. mutans, S. mitis
24
Periodontal and gingival diseases
In vivo Rats were challenged with S. mutans and fed a diet rich
in sucrose
TQ had significantly lowered periodontal indices and
subgingival bacterial count in comparison with both the
negative and positive control groups
13
In vivo Rat periodontitis model. e gingival margins of the
rat’s molars were ligated with a 4/0 silk suture to induce
periodontitis
e oral administration of TQ helped in periodontal
disease prevention as it diminishes alveolar bone
resorption
32
In vivo Clinical randomized single-blind split mouth trial
(human)
e results showed significant gains in the clinical
attachment in the TQ groups compared with other
groups
26
242
N. sativa and thymoquinone in oral health ... Al-Attas et al
Saudi Med J 2016; Vol. 37 (3) www.smj.org.sa
various diseases and conditions.42 Oral and dental
diseases have not been an exception. e literature
reported several primary studies1,13,18,24,26,32,33,36,39,40 that
investigated the role of NS and its active constituent
TQ in different areas of dentistry. Interestingly, the
results were positive and promising (Tables 2 & 3). e
NS and TQ demonstrated several potential therapeutic
effects on different oral and dental diseases. e NS and
TQ possess antiplaque activity, thus, they can help in
preventing both caries and periodontal diseases. Several
studies assessed the sensitivity of oral pathogens against
NS extracts and/or TQ, and the results were equivalent
to, synergistic with, or even better than the regularly
used antibiotics, such as amoxicillin or tetracycline.22,25
In addition, the seed extracts have anticandidal
activity, as well as wound and bone healing promoting
activities.42,51 Such results are encouraging for the
incorporation of these plants in dental therapeutics and
hygiene products. However, there were few studies, and
they were mainly conducted on animals. erefore,
more clinically controlled trials on humans are needed,
especially because the plant has no toxicity or health
hazards that have been reported by any researchers
who have been working on related clinical trials for
years.7,70 ere are still several plant properties that
are not well studied in relation to dental health or
diseases, including the anti-inflammatory and analgesic
effects.4,71 is could furnish the basis for a good
natural analgesic for toothache treatment. Additionally,
the immunomodulatory activity,72,73 makes the seed a
good alternative for oral immune diseases, as well as its
antioxidant and its antineoplastic activities, which have
been extensively studied in relation to several cancers,
including oral cancer.3,53-68 Moreover, further detailed
preclinical and clinical studies are required at the cellular
and molecular levels to investigate the mechanisms
of action of NS and its constituents, particularly TQ.
Overall, the studies that investigated the role of NS and
its active component TQ are preliminary, but the results
revealed that the plant has a potential therapeutic effect
for oral and dental diseases.
References
1. Abd-Awn B, Al-Dhaher Z, Al-Dafaai R. e effect of black
seed oil extracts on mutans streptococci in comparison to
chlorhexidine gluconate (in vitro). Journal of Baghdad College
of Dentistry 2012; 24: 126-131.
2. World Health Organization. Traditional medicine strategy
2002-2005. Geneva (CH): WHO Publications; 2002. p. 1-6.
3. Ahmad I, Tripathi J, Sharma M, Karchulli MS, Umer L. Nigella
sativa - a medicinal herb with immense therapeutic potential
(a systematic review). International Journal of Biological &
Pharmaceutical Research 2014; 5: 755-762.
4. Ahmad A, Husain A, Mujeeb M, Khan S, Najmi A, Siddique
N, et al. A review on therapeutic potential of Nigella sativa: a
miracle herb. Asian Pac J Trop Biomed 2013; 3: 337-352.
5. Tariq M. Nigella sativa feeds: folklore treatment in modern day
medicine. Saudi J Gastroenterol 2008; 14: 105-106.
6. Shrivastava R, Agrawal R, Parveen Z. A review on therapeutic
applications of Nigella Sativa. Journal of Chemistry and
Chemical Sciences 2011; 1: 241-248.
7. Gaur S, Shrivastava B, Gaur S, Bhardwaj R, Khanchandani
R. Medicinal and therapeutical potential of Nigella sativa.
International Journal of Medical and Applied Sciences Research
2014; 1: 32-39.
Table 3 - e effects of Nigella sativa (NS) extracts and thymoquinone (TQ) in common oral diseases.
Disease type Experimental model Treatment effects Reference
Pulpal diseases
In vitro Agar well diffusion method was used to test
antibacterial effects of different concentrations of NS
aqueous extract against root canal bacteria isolated
from 20 patients
e NS aqueous extract showed a maximum inhibition
zone on Enterobacter cloacae at 100% concentration
compared to other plants. e NS aqueous extract had
antibacterial effect on Streptococcus oralis, Streptococcus
anginosus, Staphylococcus epidermides and Enterococcus
durans
33
In vivo Coronal access cavities were performed in dog teeth
and the alternate sides of the mouth were treated with
NS oil and formocresol
ey reported that NS specimen histologically revealed
vasodilatation that is mild to moderate with few
inflammatory cells and a continuous odontoblastic
layer compared to the formocresol specimen, which
showed moderate to severe vasodilatation with high
inflammatory cell infiltrates and degenerative changes
36
Oral ulcerations
In vivo Rabbits were induced to have oral ulcers by injecting
0.3 ml 1% formalin and divided into control and
treated groups
e results showed significant enhancement of the
healing process with NS treatment.
39
Oral mucositis
In vivo Male albino rats were intraperitoneally injected with
5- fluorouracil to induce mucositis
NS decreased the histologically observed damage of the
mucositis cheek mucosa model
40
243
www.smj.org.sa Saudi Med J 2016; Vol. 37 (3)
N. sativa and thymoquinone in oral health ... Al-Attas et al
8. Tembhurne S, Feroz S, More B, Sakarkar D. A review on
therapeutic potential of Nigella sativa (kalonji) seeds. Journal of
Medicinal Plants Research 2014; 8: 167-177.
9. Rahmani AH, Alzohairy MA, Khan MA, Aly SM. Nigella
Sativa and its active constituents thymoquinone shows pivotal
role in the diseases prevention and treatment. Asian Journal of
Pharmaceutical and Clinical Research 2015; 8: 48-53.
10. de Oliveira JR1, de Castro VC, das Graças Figueiredo Vilela
P, Camargo SE, Carvalho CA, Jorge AO, et al. Cytotoxicity of
Brazilian plant extracts against oral microorganisms of interest
to dentistry. BMC Complement Altern Med 2013; 13: 208.
11. Ocheng F, Bwanga F, Joloba M, Borg-Karlson AK, Gustafsson
A, Obua C. Antibacterial activities of extracts from Ugandan
medicinal plants used for oral care. J Ethnopharmacol 2014;
155: 852-855.
12. Haque, M, Alsareii S. A review of the therapeutic effects of
using miswak (Salvadora Persica) on oral health. Saudi Med J
2015; 36: 530-543.
13. Shaker A, Al-Wafi H. Benefits of thymoquinone, a Nigella Sativa
extract in preventing dental caries initiation and improving
gingival health. ProQuest LLC 2014: 72.
14. Gómez SI, Jaramillo LM, Moreno GC, Roa NS, Rodríguez
A. Differential reactivity of salivary IgA and IgG against
Streptococcus mutans proteins in humans with different caries
experience. Acta Odontol Latinoam 2015; 28: 3-12.
15. Angius F, Madeddu MA, Pompei R. Nutritionally variant
streptococci interfere with streptococcus mutans adhesion
properties and biofilm formation. New Microbiol 2015; 38:
259-266.
16. World Health Organization. Oral Health Fact Sheet 318.
Geneva (CH): World Health Organization; 2012.
17. Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque
activity of Azadirachta indica leaf extract gel a 6-week clinical
study. J Ethnopharmacol 2004; 90: 99-103.
18. Harzallah H, Kouidhi B, Flamini G, Bakhrouf A, Mahjoub
T. Chemical composition, antimicrobial potential against
cariogenic bacteria and cytotoxic activity of Tunisian Nigella
sativa essential oil and thymoquinone. Food Chemistry 2011;
129: 1469-1474.
19. Gupta P, Gupta N, Pawar AP, Birajdar SS, Natt AS, Singh HP.
Role of sugar and sugar substitutes in dental caries: a review.
ISRN Dent 2013; 2013: 519421.
20. Mazumdar M, Chatterjee A, Majumdar S, Chandrika M, Patki
PS. Evaluation of the Safety and Efficacy of Complete Care
Herbal Toothpaste in Controlling Dental Plaque, Gingival
Bleeding and Periodontal Diseases. J Homeop Ayurv Med 2013;
2: 124.
21. Khalid A, Rehman U, Sethi A, Khilji S, Urooj F, Khan M, et
al. Antimicrobial activity analysis of extracts of Acacia modesta,
Artimisia absinthium, Nigella sativa and Saussurea lappa against
Gram positive and Gram negative microorganisms. African
Journal of Biotechnology 2011; 10: 4574-4580.
22. Kouidhi B, Zmantar T, Jrah H, Souiden Y, Chaieb K,
Mahdouani K, et al. Antibacterial and resistance-modifying
activities of thymoquinone against oral pathogens. Ann Clin
Microbiol Antimicrob 2011; 10: 29.
23. Bakathir HA, Abbas NA. Detection of the antibacterial effect of
Nigella sativa ground seeds with water. Afr J Tradit Complement
Altern Med 2011; 8: 159-164.
24. Mohammed NA. Effect of Nigella Sativa L. extracts against
streptococcus mutans and streptococcus mitis in vitro. Journal
of Baghdad College of Dentistry 2012; 24: 154-157.
25. Lucas VS, Roberts GJ. Oro-dental health in children with
chronic renal failure and after renal transplantation: a clinical
review. Pediatr Nephrol 2005; 20: 1388-1394.
26. Al-Bayaty F, Kamaruddin A, Ismail M, Abdulla M.
Formulation and Evaluation of a New Biodegradable
Periodontal Chip Containing ymoquinone in a Chitosan
Base for the Management of Chronic Periodontitis. Journal of
Nanomaterials 2013; 2013: 397308.
27. Loos BG. Systemic effects of periodontitis. Int J Dent Hyg
2006; 4: 34-38.
28. Bokhari SA, Khan AA. Growing burden of noncommunicable
diseases: the contributory role of oral diseases, Eastern
Mediterranean Region perspective. East Mediterr Health J
2009; 15: 1011-1020.
29. Wahid A, Chaudhry S, Ehsan A, Butt S, Khan AA. Bidirectional
relationship between chronic kidney disease and periodontal
disease. Pak J Med Sci 2013; 29: 211-215.
30. Haas AN, Pannuti CM, Andrade AKP, Escobar EC, Almeida ER,
Costa FO, et al. Mouthwashes for the control of supragingival
biofilm and gingivitis in orthodontic patients: evidence-based
recommendations for clinicians. Braz Oral Res 2014; 28: 1-8.
31. Van Leeuwen MP, Slot DE, Van der Weijden GA. Essential
oils compared to chlorhexidine with respect to plaque and
parameters of gingival inflammation: a systematic review. J
Periodontol 2011; 82: 174-194.
32. Ozdemir H, Kara MI, Erciyas K, Ozer H, Ay S. Preventive effects
of thymoquinone in a rat periodontitis model: a morphometric
and histopathological study. J Periodontal Res 2012; 47: 74-80.
33. Nader MI, Al-waini AN, Abdul-Hassan IA, Ali AW. Effect
of Nigella Sativa (black seed), Salvadora Persica (Siwak) and
aluminum potassium sulphate (ALUM) aqueous extracts on
isolated bacteria from teeth root canal. Iraqi J Biotech 2010; 9:
99-104.
34. Senia ES, Marshall FJ, Rosen S. e solvent action of sodium
hypochlorite on pulp tissue of extracted teeth. Oral Surg Oral
Med Oral Pathol 1971; 31: 96-103.
35. Jhajharia K, Parolia A, Shetty KV, Mehta LK. Biofilm in
endodontics: A review. J Int Soc Prev Community Dent 2015;
5: 1-12.
36. Omar OM, Khattab NM, Khater DS. Nigella Sativa oil as a
pulp medicament for pulpotomized teeth: a histopathological
evaluation. J Clin Pediatr Dent 2012; 36: 335-342.
37. Porter SR, Leao JC. Review article: oral ulcers and its relevance
to systemic disorders. Aliment Pharmacol er 2005; 21:
295-306.
38. Muñoz-Corcuera M, Esparza-Gómez G, González-Moles MA,
Bascones-Martínez A. Oral ulcers: clinical aspects. A tool for
dermatologists. Part I. Acute ulcers. Clin Exp Dermatol 2009;
34: 289-294.
39. Al-Douri A, Al-Kazaz S. e effect of Nigella Sativa oil (black
seed) on the healing of chemically induced oral ulcer in rabbit
(experimental study). Al-Rafidain Dent J 2010; 10: 151-157.
40. Lotfy AO, Zayed M. Immunohistochemical study of the
effect of Nigella Sativa L extract on chemotherapy induced
oral mucositis in Albino rats. Cairo Dental Journal 2009; 25:
159-166.
41. Ab Rahman MR, Abdul Razak F, Mohd Bakri M. Evaluation
of wound closure activity of Nigella sativa, Melastoma
malabathricum, Pluchea indica, and Piper sarmentosum extracts
on scratched monolayer of human gingival fibroblasts. Evid
Based Complement Alternat Med 2014; 2014: 190342.
244
N. sativa and thymoquinone in oral health ... Al-Attas et al
Saudi Med J 2016; Vol. 37 (3) www.smj.org.sa
42. Al-Hijazi AY, Mohammed HS. Evaluation of the effect of
Nigella Sativa oil and powder on socket healing process. Journal
of Natural Sciences Research 2013; 13: 135-141.
43. Alnajar SSA, Mohammed SA. Mechanical and histological
significance of Nigella Sativa oil extract on bone-implant
interface. Journal of Baghdad College of Dentistry 2009; 21:
39-43.
44. El-Sweify AA, Hassan MM, Ahmed IH, Basha AA. Comparative
study between the effect of calcium hydroxide mixed with
Nigella Sativa oil versus bioglass on healing of induced
mandibular bone defects in rats. SCVMJ 2008; 13: 449-459.
45. Laysar HA, Niakan M, Taghi GM, Jafarian Z, Mostafavizade
M, Niakan S. Comparison of the antibacterial activity of various
concentrations of Nigella Sativa and Nanosilver on the growth
of S. sanguis and S. mutans. J Res Dent Sci 2013; 9: 179-186.
46. Farah CS, Lynch N, McCullough MJ. Oral fungal infections:
an update for the general practitioner. Aust Dent J 2010; 55
Suppl 1: 48-54.
47. Fani MM, Kohanteb J, Dayaghi M. Inhibitory activity of garlic
(Allium sativum) extract on multidrug-resistant Streptococcus
mutans. J Indian Soc Pedod Prev Dent 2007; 25: 164-168.
48. Alsaidy D. Isolate, Diagnosis and Treatment of Yeast Candida
albicans accompanying the human body. International Journal
of Advanced Research 2014; 2: 1081-1086.
49. Doudi M, Setorki M, Hoveyda L. Comparing the antifungal
effects of five essential oils plants eucalyptus, cinnamon,
wormwood, sagebrush and iranian rose damascena on three
standard strains of candida albicans in vitro. International
Journal of Biology, Pharmacy and Allied Sciences 2014; 3:
490-500.
50. Fareid MA. In vitro: evaluation of inhibitory activity of some
plant extracts against oral candidiasis. New York Science Journal
2014; 7: 66-76.
51. Randhawa MA, Gondal M, Al-Zahrani A, Rashid SG, Ali
A. Synthesis, morphology and antifungal activity of nano-
particulated amphotericin-B, ketoconazole and thymoquinone
against Candida albicans yeasts and Candida biofilm. J Environ
Sci Health A Tox Hazard Subst Environ Eng 2015; 50: 119-124.
52. Califano J, van der Riet P, Westra W, Nawroz H, Clayman G,
Piantadosi S, et al. Genetic progression model for head and
neck cancer: implications for field cancerization. Cancer Res
1996; 56: 2488-2492.
53. Jaiswal G, Jaiswal S, Kumar R, Sharma A. Field cancerization:
concept and clinical implications in head and neck squamous
cell carcinoma. J Exp er Oncol 2013; 10: 209-214.
54. Arnaoutakis D, Bishop J, Westra W, Califano JA. Recurrence
patterns and management of oral cavity premalignant lesions.
Oral Oncol 2013; 49: 814-817.
55. Kuriakose MA, Sharan R. Oral cancer prevention. Oral
Maxillofac Surg Clin North Am 2006; 18: 493-511.
56. Khan Z, Bisen PS. Oncoapoptotic signaling and deregulated
target genes in cancers: special reference to oral cancer. Biochim
Biophys Acta 2013; 1836: 123-145.
57. Saba NF, Haigentz M Jr., Vermorken JB, Strojan P, Bossi P,
Rinaldo A, et al. Prevention of head and neck squamous cell
carcinoma: removing the “chemo” from “chemoprevention”.
Oral Oncol 2015; 51: 112-118.
58. ompson L. World Health Organization classification of
tumours: pathology and genetics of head and neck tumours.
Ear Nose roat J 2006; 85: 74.
59. Brown RK, Wilson G, Tucci MA, Benghuzzi HA. e
effects of thymoquinone and Doxorubicin on leukemia and
cardiomyocyte cell lines. Biomed Sci Instrum 2014; 50:
391-396.
60. Chu SC, Hsieh YS, Yu CC, Lai YY, Chen PN. ymoquinone
induces cell death in human squamous carcinoma cells via
caspase activation-dependent apoptosis and LC3-II activation-
dependent autophagy. PloS One 2014; 9: e101579.
61. Sutton KM, Greenshields AL, Hoskin DW. ymoquinone, a
bioactive component of black caraway seeds, causes G1 phase
cell cycle arrest and apoptosis in triple-negative breast cancer
cells with mutant p53. Nutr Cancer 2014; 66: 408-418.
62. Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock
H. ymoquinone and cisplatin as a therapeutic combination
in lung cancer: in vitro and in vivo. J Exp Clin Cancer Res 2010;
29: 87.
63. Rajkamal G, Suresh K, Sugunadevi G, Vijayaanand MA,
Rajalingam K. Evaluation of chemopreventive effects of
ymoquinone on cell surface glycoconjugates and cytokeratin
expression during DMBA induced hamster buccal pouch
carcinogenesis. BMB Rep 2010; 43: 664-669.
64. Abdelfadil E, Cheng YH, Bau DT, Ting WJ, Chen LM, Hsu
HH, et al. ymoquinone induces apoptosis in oral cancer
cells through p38beta inhibition. Am J Chin Med 2013; 41:
683-696.
65. Speirs CK, Hwang M, Kim S, Li W, Chang S, Varki V, et al.
Harnessing the cell death pathway for targeted cancer treatment.
Am J Cancer Res 2011; 1: 43-61.
66. Gewirtz DA. Cytoprotective and nonprotective autophagy in
cancer therapy. Autophagy 2013; 9: 1263-1265.
67. Gali-Muhtasib HU, Abou Kheir WG, Kheir LA, Darwiche N,
Crooks PA. Molecular pathway for thymoquinone-induced
cell-cycle arrest and apoptosis in neoplastic keratinocytes.
Anticancer Drugs 2004; 15: 389-399.
68. ElKhoely A, Hafez HF, Ashmawy AM, Badary O, Abdelaziz A,
Mostafa A, et al. Chemopreventive and therapeutic potentials
of thymoquinone in HepG2 cells: mechanistic perspectives. J
Nat Med 2015; 69: 313-323.
69. Al-Attas SA, Munshi A, Noorwali A, Algrigri MA, Abohager
EA, Zahran FM. Nigella sativa extract chemoprevention in oral
cancer: in vivo study. Advances in Environmental Biology 2015;
9: 75-90.
70. Al-Quorain AA. Nigella Sativa. Saudi J Med Med Sci 2015; 3:
1.
71. Bashir MU, Qureshi HJ. Analgesic effect of Nigella sativa seeds
extract on experimentally induced pain in albino mice. J Coll
Physicians Surg Pak 2010; 20: 464-467.
72. Osman MT, Hamza AJ, Omar E, Adnan A. e new miracle
of Habbatus Sauda: its major component thymoquinone can
be used in the management of autoimmune diseases. Procedia
-Social and Behavioral Sciences 2014; 121: 304-314.
73. Salem ML. Immunomodulatory and therapeutic properties
of the Nigella sativa L. seed. Int Immunopharmacol 2005; 5:
1749-1770.
... Traditionally it has been used to treat various diseases, such as headaches, influenza, dyspepsia, diabetes, and asthma [16]. Black seed extract has been confirmed to improve oral health and reduce dental caries, [17] periodontitis, gingivitis, and pulp diseases [18]. ...
... Thymoquinone (TQ) is the core ingredient of the black seed oil extract with proven medical benefits [19]. The literature suggested a significant decrease in the count of S. mutans when exposed to TQ [17]. ...
... Our result is in line with the previous results, showing antibacterial activity, minimum inhibitory effect, and being more tolerant than the rest of the three, S. oralis, S. mutans and S. salivarius, bacterial strains [36,37]. While S. aureus has shown resistance against common antimicrobial treatments, an increase in the dose of TQ has been effective in reducing the bacterial count and growth; TQ could be the answer to overcoming this strand's high resistance [17,18,28]. ...
Article
Full-text available
This study aimed to evaluate the antimicrobial effect of Thymoquinone (TQ) on four different oral microorganisms. Minimum Bactericidal Concentration (MBC), Minimum Inhibition Concentration (MIC), Broth microdilution, and Well diffusion tests were used to determine the optimum antimicrobial concentrations of TQ against Streptococcus salivarius, Streptococcus oralis, Streptococcus mutans, and Staphylococcus aureus over 1, 3, 6, 12 and 24 h. Chlorhexidine 0.12% was selected as a positive control. The inhibitory effect of TQ on bacterial growth was most noticeable with S. salivarius, while the least affected was S. aureus. TQ’s MBC and MIC for S. oralis and S. aureus were comparable 2 mg/mL and 3 mg/mL, respectively. S. salivarius was most resistant to TQ and displayed a value of 5 mg/mL and 4 mg/mL for MIC and MBC, respectively. The viable count of different strains after exposure to TQ’s MBC values was most noticeable with S. aureus followed by S. oralis and S. mutans, while S. salivarius was least affected. This study emphasized the promising antimicrobial effect of TQ against the four main oral microorganisms. It has a potential preventive effect against dental caries as well as other oral diseases.
... Thymoquinone (TQ), di-thymoquinone, fixed oils, alkaloids, flavonoids, proteins, fatty acids, saponins, and alpha-hederin 15 . TQ is the most pharmacologically active component (Figure 1) 1,16,17 . The important properties exhibited by TQ include its anti-inflammatory, analgesic, immunomodulatory, anti-oxidant, anti-cancer, anti-diabetic and anti-hypertensive activities 3,18-20 . ...
... The implications of NSO in dentistry can be ascertained by detailed preclinical and clinical studies at the cellular and molecular levels to investigate the mechanism of action of NSO in the treatment of periodontal diseases. NSO can be used alone or in suitable combinations with other existing drugs for the effective treatment of infectious dental diseases in a manner that can overcome the problem of drug resistance [13][14][15][16][17]. ...
Article
Full-text available
The present study aimed to develop a local dental nanoemulgel formulation of Nigella sativa oil (NSO) for the treatment of periodontal diseases. NSO purchased from a local market was characterized using a GC–MS technique. A nanoemulsion containing NSO was prepared and incorporated into a methylcellulose gel base to develop the nanoemulgel formulation. The developed formulation was optimized using a Box–Behnken statistical design (quadratic model) with 17 runs. The effects of independent factors, such as water, oil, and polymer concentrations, were studied on two dependent responses, pH and viscosity. The optimized formulation was further evaluated for droplet size, drug release, stability, and antimicrobial efficacy. The developed formulation had a pH of 7.37, viscosity of 2343 cp, and droplet size of 342 ± 36.6 nm. Sustained release of the drug from the gel for up to 8 h was observed, which followed Higuchi release kinetics with non-Fickian diffusion. The developed nanoemulgel formulation showed improved antimicrobial activity compared to the plain NSO. Given the increasing emergence of periodontal diseases and antimicrobial resistance, an effective formulation based on a natural antibacterial agent is warranted as a dental therapeutic agent.
... Periodontal disease activates inflammatory and immune mechanisms that play a role in the development of systemic disease (Wada & Kamisaki, 2010). Moreover, periodontitis is defined as an inflammatory disease caused by bacteria that destroy the gingiva around the teeth (AlAttas et al., 2016). Inflammation in periodontitis is triggered by organisms in oral microbial biofilms, particularly gram-negative anaerobes such as P. gingivalis (Mekhemar et al., 2020). ...
Article
Objective Periodontitis is an infectious disease that results in gingiva tissue damage. This study aimed to evaluate the effects of Nigella sativa (N. sativa) toothpaste in a periodontitis tissue repair based on inflammation and periodontal extracellular matrix in vivo. Design The periodontitis disease model was developed using Wistar rats infected with Porphyromonas gingivalis (P. gingivalis). The rats were divided into three main groups as follows: those that did not receive any toothpaste treatment; those that were treated with N. sativa toothpaste twice a day (simultaneously with P. gingivalis induction); and normal healthy rats. The rats were sacrificed after 1 and 7 days of animal modelling. The number of inflammatory cells, matrix metalloproteinase (MMP)1+ and MMP8+ cells, levels of cytokines (interleukin-1β (IL-1β) and prostaglandin E2 (PGE2)) and density of collagen type 1 were determined in the gingival tissues of the rats. Results The rats treated with N. sativa toothpaste had significantly lower numbers of neutrophils, macrophages and lymphocytes than the non-treated rats after 1 and 7 days of treatment; likewise, the levels of IL-1β and PGE2 were lower in the treated experimental rats. In addition, the group treated with N. sativa toothpaste had fewer numbers of MMP1+ and MMP8+ cells and higher collagen density after 1 and 7 days of administration. Conclusions N. sativa toothpaste exhibited anti-inflammatory effects by reducing both inflammatory cell count and activity. Additionally, N. sativa toothpaste demonstrated anti-destructive effects on the periodontal extracellular matrix. Thus, N. sativa toothpaste might be potentially used for the management of periodontitis.
... Subsequently, the tooth socket heals secondarily in ten to fourteen days with variable severity of pain continued throughout this healing period [10,11]. To enhance the efficacy of healthcare, the World Health Organization (WHO) has encouraged developing countries to integrate the use of therapeutic plants since more than two-thirds of their population depends on the use of natural remedies and traditional herbs for disease treatment [12,13]. ...
Article
Full-text available
Introduction. Alveolar Osteitis (AO) is the most common complication faced by exodontia patients and is usually seen 24-74 hours after tooth extraction, heralded by severe throbbing pain. Nigella sativa is commonly known as a black seed known to have anti-inflammatory, antibacterial properties along with other-reparative properties that enhance bone formation. This study aimed to evaluate and compare the effect of alvogyl and a mixture of Nigella Sativa powder and oil in the treatment of dry sockets. Material and Methods. This study aimed to evaluate and compare the effect of Alvogyl and a Mixture of Nigella Sativa’s powder and oil in the treatment of dry sockets. Sixty patients above the age of 18 and below 70 years, from both genders, who underwent extraction of teeth and are clinically diagnosed with a dry socket at the clinic of College of Dentistry, Jouf University, Saudi Arabia were included in this study. Pain scores were assessed after placement of dressing at the following intervals: 5 minutes, 30 minutes, 60 minutes, 2nd Day, 4th Day, and 7th Day. Patients were randomly allocated to three groups namely Group 1 (Alvogyl), Group 2 (Mixture of Nigella Sativa’s powder and oil), Group 3 (Control). Pain relief and healing of the socket were compared between the three groups. The collected data were subjected to statistical analysis through Spearman’s correlation test, independent t-test, ANOVA, and post-hoc test. Results. A mixture of Nigella Sativa powder and oil showed a statistically significant difference in relieving pain compared to the Alvogyl group. A mixture of Nigella Sativa’s powder and oil required fewer dressings when compared to the Alvogyl group. Conclusion. A mixture of Nigella Sativa powder and oil is the more efficacious dressing material for the management of dry sockets compared to Alvogyl. It provides immediate complete pain relief and fewer numbers of repeated visits.
... N. sativa is also known as black cumin seed, which is a widely used medicinal plant throughout the world and an important ingredient in Indian cooking (Hassanien et al., 2015). It has been used as a natural remedy for the treatment of fever, common cold, headache, asthma, rheumatic diseases, microbial infections and to expel worms from the intestine (Al-Attass et al., 2016;Hassanien et al., 2015). Several components of black cumin have been identified, including thymoquinone, thymol, thymohydroquinone, and dithymquinone (Morikawa et al., 2004). ...
Article
Full-text available
Nigella Sativa (N. sativa) also known as black cumin seed and their active component thymoquinone are used as anti-inflammatory, antimicrobial and anticancer treatments. This study was aimed to synthesizes, characterize and to compare the antibacterial and anticancer activity of biologically synthesized nano thymoquinone (Tb-NPs) and chemically synthesized nano thymoquinone (Tc-NPs). The synthesis of nano-thymoquinone (nTQ) by chemical method was based on wet milling technique and biological method was using N. sativa seeds extract. The synthesized nTQ was characterized by UV, FTIR and FESEM analysis. The antimicrobial effects of Tc-NPs and Tb-NPs were evaluated against common antibiotic resistant organisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococci faecalis, Klebsiella species and E. coli) using agar well diffusion. The results obtained from the UV spectra analysis showed highly intense absorption for both Tb-NPs and Tc-NPs at 242 nm and 319 nm respectively. The FTIR spectrum for Tb-NPs and Tc-NPs showed characteristics peaks at five different regions. The FESEM analysis of Tc-NPs showed micro/nano fibers and were homogeneously distributed and Tb-NPs showed spherical and agglomerates that were unevenly distributed. The cytotoxicity assay showed potential anticancer activity of Tb NPs with minimal concentration that of Tc NPs. Additionally these nTQ particles showed antimicrobial activity with removal of potential of bacterial and fungal pathogens by increased zone of inhibition. The obtained results concluded the biosynthesized nTQ have shown more activity because of the ability to remove potential of microbial pathogens and increase cancer cell death. These findings may encourage the use of biosynthesis method of nTQ over the chemosynthesis method.
Chapter
Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
Chapter
Full-text available
Harpagophytum procumbens, also known as the devil’s claw, is a species from southern and southwestern Africa. In the wild, it grows mainly in arid desert areas, specifically in the Kalahari Basin. This perennial, groundling plant belongs to the sesame (Pedaliaceae) botanical family. Dried and powdered root tubers (Harpagophyti radix) are the main medical raw material. The powder, as well as the liquid and the dry extracts are used for the production of tablets, capsules, tinctures and ointments. Healing properties are provided by biologically active substances in the roots, mainly iridoid glycosides, including: harpagoside, harpagide and procumbide, as well as phenylethanoid glycosides (verbascoside and isoverbascoside), flavonoids, triterpenes, phenolic acids, phytosterols and quinones. The minimum content of the harpagoside determines the recognition of the raw material as medicinal, and should be at least 1.2%. The devil's claw is used in herbal medicine by African and other continents inhabitants. Preparations from devil’s claw available on the market are currently very popular in the treatment of inflammatory diseases of bones and joints. Extracts of devil’s claw roots have antiinflammatory, analgesic and antioxidant properties. In addition, they have an antimicrobial effect. They are also effective in the treatment of various skin diseases and wounds. Keywords: Harpagophyti radix, iridoid glycosides, medicinal plant
Article
Full-text available
Black seed has been a plant of interest to researchers, which is largely due to its prominent constituent, thymoquinone and its therapeutic effect. Traditionally, it has been used to treat varieties of ailments such as asthma, hypertension, dia- betes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and influenza. This review attempts to suggest thymoquinone as a potential antiviral drug against COVID-19, caused by SARS CoV-2, a virus of the coronavirus family that stretches the immune system to its limits. With the current pandemic status of the disease, researchers worldwide are intensifying efforts in prospecting for solutions. Thymoquinone represents a cheap option of biological source that can be explored clinically. Based on empirical data, Thymoquinone is non-toxic and has exhibited antiviral, anti-inflammatory, antioxidative, and pneumo-protective activities and should be strongly considered for preclinical and clinical studies against SARS-CoV-2 infection. Keywords:Black seed, Thymoquinone, COVID-19, SARS-CoV-2
Article
Full-text available
Background: Seeds of Nigella sativa L., commonly known as black seed, have been used in traditional medicine. Streptococcus mutans and Streptococcus mitis are normal flora bacteria found in human oral cavity, which cause dental caries and bad breathe oder. This project considered as an explorer study for the inhibitory effect of Nigella Sativa L. seeds extract against S. mutans and S. mitis. Material and methods: Two different extracts of Nigella sativa L. has been evaluated in vitro against Streptococcus mutans & Streptococcus mitis, the antibacterial activity was determined by the agar well diffusion method. Results: The results showed the zone of inhibition was found 12.7mm and 10.4mm at a ethanol extract against Strept. mutans & Strept. mitis respectively,while the inhibition zone of ether extract was found 6.3mm and 5.1mm against Strept. mutans & Strept. mitis respectively. Conclusion: Methanol extract was more effective in comparison with the ether extracts. The highest inhibition zone was observed with ethanol fraction and it inhibited the growth of two careiogenic bacteria.
Article
Full-text available
ABSTRACT Background: The black seed or Nigella sativa has been used for centuries to promote health and fight disease. This plant has a great focus for research due to its antibacterial, antifungal, anti-tumor, and hypotensive effects. This study was conducted to assess the effect of the black seed oil extract on sensitivity of mutans streptococci and the adherence to tooth surface in comparison to chlorhexidine gluconate in vitro. Materials and methods: Four different concentrations of black seedoil extract (1%, 5%,10%, and20%) wereprepared using ethanol as a solvent for the evaluation of the antimicrobial activity of the black seed oil extract against mutans streptococci isolated from saliva of volunteers and compared with 0.2% chlorhexidine gluconate using agar diffusion test, followed by determination of the Minimum Bactericidal Concentration (MBC) of the black seed oil extract. Three concentrations (1%, 5%, and 10%) were used in the adherence study whereby a stainless steel wires were threaded from one end in the roots of previously cleaned, polished and sterilized first premolars, which were then immersed in 10 ml of the agent for 2 minutes, followed by washing with sterilized deionized water. The teeth were then immersed in 10ml Brain Heart Infusion Broth and inoculated with 2% of bacterial isolates and incubated aerobically at 37 0 C for seven days. A positive score was given to the microbial growth on wire, teeth and bottle indicatinga non-effective treatment and vice versa. Results The study showed inhibition zones for black seed oil extract which were found to be increased as the concentration of the extract increased. The MBC of the black seed oil extract against mutans streptococci was 10%. The results also showed that the oil extract was effective in inhibiting the adherence of mutans streptococci to tooth surface ata concentration of 10%. Conclusion: The black seed oil extract has a bactericidal effect against mutans streptococci at a concentration of 10%,and can inhibit the adherenceof thesemicroorganisms to tooth surface. Key words: Nigella sativa,mutans streptococci,adherence. (J Bagh Coll Dentistry 2012; 24(4):126-131).
Article
Full-text available
Swabs were taken from 20 patients from root canal (Endodontic Department, Al-Elwiya Specialized Centre for Oral and Dental Surgery), Streptococcus oralis, Streptococcus anginosus, Enterococcus durans, Enterobacter cloacae and Staphylococcus epidermides were identified according to their cultural properties, microscopic examination and biochemical Api and miniapi tests. Antibacterial action was evaluated on these bacterial isolates by using six different concentrations of Salvadora persica(Siwak), Nigella sativa (black seed), aluminum potassium sulphate (alum) and mixture of them, the concentrations are 3.125, 6.25, 12.5, 25, 50 and 100%. At 100% concentration of alum, Salvadora persica, Nigella sativa and the mixture of them, the maximum inhibition zone diameters were 42mm on Enterococcus durans, 27mm on Enterobacter cloacae, 26mm on Enterobacter cloacae and 25mm on Staphylococcus epidermides, respectively.
Article
Full-text available
Medicinal plants and its constituents used as therapeutics drugs in the health management since ancient time and large population of the world relies on traditional medicine for primary health treatment. However, medicinal plant has opened a new window of research in diseases prevention and treatment due to safe, affordable and easy to access properties. In this vista, Nigella sativa (NS) are commonly used as traditional medicines worldwide in the disease prevention due to less side-effect and affordable properties. NS and its constituents are a rich source of antioxidant, an influential free radical scavenger and also modulator of various biological activities. In this review, we summarized the therapeutics effects of black seed and its constituents in the diseases treatment and prevention through modulation of antioxidant, anti-inflammatory, anti-tumor, hepato-protective and other genetic activities.
Article
Full-text available
Article
Six ethanolic extracts from plants of Ginger (Zingiber officinale), Cinnamon (Cinnamomum verum), Black Cumin (Nigella sativa), Clove (Syzygium aromaticum), Black Pepper (Piper nigrum), and Chamomile (Anthemis nobilis) were purchased from local market in H'ail province, Saudi Arabia were assayed for the in vitro inhibitory activity against some oral Candidal isolates. The prevalence of oral candidal infections among poor control diabetes patients was higher (56%) than fair control (30%) and good control (7%) diabetes patients. Statistically, our data indicated that a higher significant difference between the prevalence of oral candidiasis and diabetic control (p-value = 0.001). Cinnamon and Clove plant extracts were the most effective of all pathogenic yeasts studied. Candida albicans, C. parapsilosis and C tropicalis showed greatest degree of sensitivity to Cinnamon and Clove plant extracts. The inhibition zone diameter recorded 34.6, 31.5; 45, 31; 45.5, 29.5 mm, respectively at 100 µg/ml concentration. Based on paired t-test, there is no significant difference between the mean values of the inhibition zone size of Amphotericin B, Black cumin, Chamomile and plant extracts were reported (P-value ˂ 0.05). Both Cinnamon and Clove extracts showed remarkable effect on C. albicans and C. tropicalis at very low concentration MIC, 15, 18 and 15, 19 μl/ml, respectively. [Mohamed A. Fareid. In Vitro: Evaluation of Inhibitory Activity of Some Plant Extracts Against Oral Candidiasis. N Y Sci J 2014;7(12):66-76]. (ISSN: 1554-0200). http://www.sciencepub.net/newyork. 9