nigella sativa a miracle herb and its role in …

www.wjpps.com │ Vol 10, Issue 11, 2021. │ ISO 9001:2015 Certified Journal │

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Ahmed et al. World Journal of Pharmacy and Pharmaceutical Sciences

NIGELLA SATIVA – A MIRACLE HERB AND ITS ROLE IN

PERIODONTAL DISEASE

1*

Dr. Syed Owais Ahmed, MDS, 2Dr. Shylesh Kumar, MDS,

3Dr. Nitin Kumar, MDS,

4Dr. Shadab Ahmed, MDS

1Assistant Professor, Dept of Periodontics, Sri Siddhartha Dental College, Tumkur,

Karnataka-572107.

2Prof & Head, Dept. of Prosthodontics, Sri Siddhartha Dental College, Tumkur, Karnataka-

572107.

3Assistant Professor, Dept of Prosthodontics, Sri Siddhartha Dental College. Tumkur,

Karnataka-572107.

4Assistant Professor, Dept of Conservative Dentistry, Sri Siddhartha Dental College. Tumkur,

Karnataka-572107.

ABSTRACT

Nigella sativa(NS) and its active constituent Thymoquininone(TQ) has

various pharmacological properties such as anti microbial, anti

inflammatory, anti cancer, anti diabetic, anti allergic and stem cell

modulating properties. Hence it has lead to a drastic incline in the

usage of the medicinal herbs as an alternative of synthetic chemical

compounds for the treatment of various chronic inflammatory

disorders. Various studies have proved the pharmacological and

therapeutic effects of Nigella Sativa in the various oral disorders. The

aim of this review is to summarize the role of Nigella sativa in

periodontal diseases by reviewing the various published reports. Even

though the data was less but the results has proved positive outcomes of the Nigella sativa in

the treatment of various oral disorders.

KEYWORDS: Nigella Sativa, Thymoquinone, Herbal agents, anti inflammatory.

INTRODUCTION

In todays modern era there is a global incline in the usage of herbal products for treating

various disorders because of the positive results and reduced adverse effects.[1]

WHO has

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 11, 676-690 Review Article ISSN 2278 – 4357

*Corresponding Author

Dr. Syed Ahmed

Assistant Professor, Dept of

Periodontics, Sri Siddhartha

Dental College, Tumkur,

Karnataka-572107.

Article Received on

03 Sept. 2021,

Revised on 24 Sept. 2021,

Accepted on 15 October 2021

DOI: 10.20959/wjpps202111-20487


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reported that more than 60% of the population especially in the developing countries utilize

medicinal herbs for the treatment of the various disorders as the primary means of treatment

and WHO has encouraged such countries to continue the use of such medicinal herbs for the

efficient health and well being.[2,3]

Among such medicinal herbs , the one herb that has gained

most attention and has more scientifically based data on its medicinal value for the treatment

of various chronic inflammatory disorder is NIGELLA SATIVA(NS) which is also known as

MIRACLE HERB of the current era.[4]

NS belongs to the family Ranunculaceae which is

annually blossoming herb. It is known by various names in various regions such as black

seeds, black caraway, black cumin seeds, habbatul barakah, kalonji, kala jeera. It is grown

and consumed more commonly in the middle east, southern asian region, mediterranean

region.[5,6,7]

In ancient days , Egyptians & Greeks have used NS seeds for the treatment of

various disorders such as head ache, tooth decay, nasal congestion, amenorrhea, parasitic

infection and to induce milk secretion of breast.[8,9]

the black seeds also has a very significant

historical, religious and spiritual background among various communities especially among

muslims population as it is linked with the famous saying of the founder of islam Prophet

Mohammed (peace be upon him) who said “USE BLACK SEEDS REGULARLY AS IT

IS CURE FOR ALL THE DISORDERS, EXCEPT DEATH”.[10]

Nigella sativa is enriched with vital nutrients such as essential oils, proteins, alkaloids,

saponins, fixed oils it also has many pharmacologically essential components such as

thymoquinone, di thymoquinone, thymol & thymohydroquinone. Nutritional components

such as carbohydrates, essential amino acids, fats, vitamins and minerals such as potassium,

calcium and iron are present in the seeds.[9]

many studies have proved that the active

component of Nigella Sativa i.e thymoquinone has various pharmacological properties such

as anti inflammatory, anti microbial, analgesics, anti hypertensive, anti glycemic, anti

carcinogenic and also as an anti oxidant.[11,12]

Periodontitis and gingivitis have inflicted the humans since the ancient times. Historical

reports have exhibited that complications that arises due to periodontal infections such as

bone loss, tooth mobility has affected the individuals globally from various cultures and

civilizations from antediluvian.[13]

The most common periodontal disease to occur is gingivitis which is an reversible condition

that occurs because of local factors especially dental plaque. In gingivitis the inflammatory


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component is not reached till the alveolar bone hence there is no bone loss or attachment loss

and the condition is reversed by removing the causative agent.

Periodontitis on the other hand is the chronic immune inflammatory disorder in which the

host response is activated against the endotoxin produced from plaque bacteria. The activated

host response act as an double edged sword which exhibits bystander effects and in turn

becomes detrimental to our own host tissues resulting in the destruction of the periodontium

resulting in periodontitis.[14]

The treatment modalities for the periodontal conditions can be broadly categorized as surgical

and non surgical treatment. Mild to moderate cases can be managed by non surgical means

whereas the progressive cases can be treated by surgical modality.[14]

In addition to the conventional periodontal treatment such as scaling & root planning for

periodontal diseases other modalities such as local drug deliveries, mouth rinses, irrigation

devices, sustained released, host modulating therapies, chemotherapeutic agents acts as

adjunct in the periodontal treatment and has exhibited beneficial results.[15]

Various studies have proved that incorporation of the chemotherapeutic agents with the

conventional mechanical therapy will serve as an apprentice for the prognosis of the

periodontal treatment.[16]

the chemotherapeutic agents that are currently incorporated in the periodontal treatment even

though they has more prompt and rapid beneficial effects but are commonly associated with

the adverse effects such as tooth discoloration, dysgeusia, drug resistance, and are not

economically feasable.[17,18]

MODALITIES AVAILABLE FOR THE PERIODONTAL TREATMENT

a) Mechanical Therapy

Periodontal disease is an multi factorial disorder where dental plaque and its microbial

content plays an vital role in the initiation of the disease. Further progression of this disease

in influenced by various factors such as systemic diseases, socio economic status, stress,

smoking, genetic factors etc…hence the treatment of periodontal disease and the good

prognosis is not an single line of treatment but it is an combination of various treatment

strategies and modalities and also depends upon patient education, motivation and patient co

ordination.


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To stop the initiation of the periodontal disease the local factors such as plaque and calculus

has to be removed which can be best done by the mechanical therapy i.e scaling and root

planning.

Scaling and root planning has become a gold standard for removal of the plaque and calculus

from the tooth surface. Various studies have shown that it significantly decreases the amount

of bacterial burden in the periodontal pocket and results in the decrease of the periodontal

clinical parameter such as probing depth, mobility, bleeding on probing and attachment

loss.[19]

b) PERIODONTAL THERAPY WITH CHEMOTHERAPEUTIC AGENTS

Antimicrobial Agents

Even though mechanical debridement tends to eradicate most of the bacterial plaque and its

content from the periodontal pocket but still certain periodontal pathogens have tissue

penetrating capacity that tend to invade deep inside the host tissues and which is practically

not possible to remove with the mechanical therapy alone. Hence antimicrobial agents are

required to deliver either systemically or locally to eradicate the bacteria deep inside the

tissue.

Most of the time after the mechanical therapy the periodontal pathogens in the pocket

environment tend to repopulate the site within few weeks resulting in reactivation of

disease.[20]

Concomittent incorporation of the systemic antimicrobial agents as adjunct to the mechanical

therapy results in better eradication of the bacteria deep inside the tissue and has exhibited

positive results.[21]

Although the systemic antimicrobial agents has shown beneficial results its use is mostly

confined only to rapid progressive and refractory cases because of the simultaneous

detrimental adverse effects.[22,23]

The major draw back of the systemic administration of the antimicrobial agents include,

decrease absorbtion of the drug at the target site, decrease plasma concentration because of

firstpass metabolism below the therapeutic index which is not effective and if given in higher

dose it may have serious side effects.[24,23]


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To overcome this side effects of the systemic antimicrobials research has lead to the

development of the local drug delivery which can be directly targeted into the pocket area so

that adequate concentration of the drug to inhibit the periodontal pathogen is achived and the

systemic complications of the antimicrobials are avoided.[23]

c) HOST MODULATION THERAPY

Recent research has stated that periodontal disease is an immune inflammatory disorder in

which the host response is activated in response to the bacterial endotoxins liberated from

gram negative periodontal pathogens. The activated host response produces various chemical

mediators to kill the bacteria or neutralize the toxins. These chemical mediators exhibit

bystander effect to the host tissues thus apart from being detrimental to the pathogens it even

destroy the own host tissues.

Host modulation therapy aims at the down regulation of the inflammatory part of the host

response by targeting the pro inflammatory cytokines without affecting the natural immune

system thus minimizing the inflammatory reaction mediated destruction of host.[25]

various

chemotherapeutic agents are available for the host modulation therapy, that can be

administered locally or parentally which will benefit the host by down regulating the pro

inflammatory cytokines and can give additive beneficial effect for mechanical therapy.[26,27]

Modalities available for the host modulation available are sub anti microbial dose of

doxicycline(SDD)[27]

, NSAIDS, Bisphosphonates, growth factors[29]

, anti cytokines drugs[28]

,

enamel matrix derivative.[29]

etc..

These agents modulate the host response by various methods such as by blocking

prostaglandin by the NSAID, blocking inflammatory cytokines by anti cytokine therapy,

suppressing matrix metalloproteinase by the SDD, down regulating the activity of the

osteoclasts by the bisphosphonates.

d) PERIODONTAL THERAPY BY HERBAL AGENTS

Herbal therapeutic agents contains natural alkaloids and elements that were belive to have

medicinal and therapeutic value from the ancient times.[13]

As the herbal products exhibit

lesser adverse effect ,drug resistance and addiction when compared to chemotherapeutic

agents and as it has shown more positive results there is rapid increase in the use of the herbal

medicines all around the world.[13]

because of these advantages the use of herbal medicinal


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products are being incorporated in the periodontal therapy as an adjunct to the conventional

mechanical therapy.[30]

Various herbs are being used in the periodontal treatment and among such herbal remedies

one of the most promising and the most interesting herb which has given more promising

results is Nigella Sativa (NS). This herb is widely used globally for various ailments and

chronic illness.[31]

NIGELLA SATIVA

NS is classified under the kingdom PLANTAE and its sub kingdom is Tracheobionata. The

supervision of the NS is under spermatophyte and its order is rananculels. The family of NS

is ranunculacea-the butter cup family, genera is Nigella, and species is N.sativa.

Biologically Active Compounds In Nigella Sativa

NS has been studied and investigated from ages and modern day studies have researched and

proved that black seed oil is the most biologically active and important component of the NS.

The beneficial effects of the NS is due to the presence of the biologically active compound i.e

thymoquinone, which makes up 50% of the total content of the NS oil.[32]

In additional to the TQ the other active compounds present in the NS oil is carvacrol,

thymohydroquinone, dihydrothymoquinone, thymol, t-anethole, α-pinene, β-pinene, α-

thujene,[33]

The therapeutic advantages of the NS oil is mainly due to the presence of TQ. TQ exhibit

various pharmacological effects such as anti inflammatory, anti oxidative, anti microbial, anti

hypertensive, hypoglycemic, hepatoprotective and anti carcinogenic effects.

CHEMICAL COMPOSITION AND STRUCTURE

The chemical composition of NS seeds consist of Proteins, Carbohydrates, fats, crude fibers

& total ash. Among those there are many therapeutically active compounds.

TQ is the most bioactive component of the NS. Its molecular mass is 164.20 ng/dl.[34]

It has

the molecular formula of C10 H12 O2. the concentration of the TQ in the NS oil is 18 and 25

µg/dl.[35]


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The bioavailability of the TQ is diminished by its hydrophobic properties. TQ can be

administered through various routes which includes oral, Parental, intra peritoneal, intra

venous and localized drug delivery.

Role of Nigella Sativa in Treatment of Peripodontaldiseases

The role of Nigella sativa and its active ingredients such as TQ in the treatment of the

periodontal diseases has been investigated at an very broader scale. Various studies has

shown the positive and beneficial effects of the NS in the periodontal therapy as an adjunct to

mechanical therapy.

Various studies has been conducted with the local application of the NS i.e its active

compound TQ in the concentration of 0.1to 0.2%[36,37,38]

in the form of the gel. And also in

the form of the customized biodegradable chips in the concentration of 2.5mg[39]

of TQ. some

studies has been done with the 2% and 0.1 to 10% of the usage of the NS solution.[40,41]

all

these concentrations and means of drug delivery proved to be beneficial in the reduction of

the periodontal clinical parameters such as PPD, BOP, GI, PI and resulted in the gain of the

clinical attachment gain.

Inflammatory mediators profile of the GCF such as cytokines, interleukins, ALP levels were

declined after the use of the NS. Anti microbial component profile of the GCF and the

histological sections of the gingival sulcus has also showed positive results after the

incorporation of the NS and its component in the periodontal therapy.[42]

Therapeutic properties of NS

1) Down regulation of pro inflammatory cytokines.

Production of pro inflammatory cytokines and inflammatory mediators and NO play an

important role in the progression of the inflammation that can have destructive effects on the

Periodontium.[43]

various studies has proved that NS and its active component TQ has the anti

inflammatory properties and it also down regulates the production of free radicals thus

decreasing the oxidative stress.[44]

2) NS suppress the production of the NO by decreasing the INOS M-RNA release by

macrophages and it also decreases the production of the inflammatory progressing

cytokines such as 1L-1b, 1L-6, TNF-α, IFN-c & PGE2 and promotes the release of the

anti inflammatory cytokines.[45,46]


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3) NS has also showed to significantly suppress the production of arachidonic acid

metabolite thus reducing the inflammatory mediated destruction of the host tissue caused

by the production of the prostaglandins.[47]

4) Animal studies conducted on rats showed that when their drinking water was incorporated

with the NS or when oral gel incorporated with NS was given to rats. They exhibited

significant decrease in the periodontal clinical parameters when compared to its normal

counter part.[48]

ANTIMICROBIAL EFFECT

Periodontal diseases is multi factorial immune inflammatory disorder that results from the

liberation of the endotoxins released by the plaque bacteria into the host tissue thus eliciting

and activating a host immune response that results in production of pro inflammatory

cytokines thus inducing a bystander effect on the host tissue resulting in the periodontal

destruction. Thus even though periodontal disease require various factors for the progression

of periodontal disease but the initiating factor remains the plaque bacteria which is microbial

in origin.

Various studies has been conducted to evaluate the efficacy of the NS and its active

component TQ against the plaque bacteria and it has proved to be more beneficial in

decreasing the periodontal pathogens, decreasing the intensity of the gingival inflammation

and reducing the periodontal clinical parameters.[49,50]

One of the way by which it exerts an antimicrobial effects against the bacteria is by

production of ROS and and concomitantly producing scavenging effects thus reducing

systemic oxidative stress.[51]

NS also weakens the integrity of the bacterial cell wall by inhibiting the efflux pump of the

bacterial cell wall, which can also be one of the reason that bacterial drug resistance is

decreased when it is combined along with NS.[52,53]

Various in vitro and animal studies has proved that application of NS and TQ for the

periodontal treatment proved to be effective against the periodontal pathogens such as

Aggregatibacter actinomycetum comitants, Porphyromonas gingivalis, Fusobacterium

nucleatum.[49,38]


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10% TQ administration has proved to drastically decrease the level of fusobacterium

nucleatum and Porphyromonas gingivalis. It also decrease the rate of bio film formation and

also causes hemolysis of both the bacteria.[41]

TQ also reduces the H2S production which is the main cause for the halitosis. It also

decreases the expression of the virulence factors from the bacterial species.[41]

EFFECT ON STEM CELL

The Periodontal regeneration depends upon the selective re population of the progenitor cells

from the periodontal ligament mainly mesenchymal stem cells which migrates and

differentiate into cementoblasts, osteoblasts and fibroblast thus forming cementum, alveolar

bone and periodontal ligament.

Various studies has observe the effect of the natural herbs, its active compounds exerting the

modulatory effects on the stem cells thus causing its migration, differentiation and

proliferation.[54,55]

In vitro studies has also showed the modulating effects of NS and TQ on the mesenchymal

stem cells which can results in better regeneration and healing outcomes.

TQ which is the active component of the NS results in activation of the c-MET & CXCR4

signalling pathways hence resulting in the enhanced migration of the MSC.

TQ also enhance the stemness of the mesenchymal stem cells by increasing the expression of

the CD markers on the cell surface of the stem cells and also increases the gene expression

both in vitro and in vivo.[56,57]

Other experimental observation has revealed that application of NS and its active compound

TQ has modulated the stem cells and increases the migration and its healing properties in the

wounded areas.[58,59]

CONCLUSION

In recent days there is an incline towards the use of the herbal medicine for various diseases

because of there lesser side effects and more promising results. Since NS and its component

has anti bacterial, anti inflammatory and immune modulatory properties as demonstrated by

various in vitro and in vivo studies it plays an vital role and act as an best adjuct to the


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standard mechanical therapy in preventing periodontal diseases and also has exhibited

optimistic results on modulating the host stem cells which can enhance the regenerative and

healing capacity. But its role in the treatment of periodontal therapy as an adjunct is yet to be

studied with more observational and longitudinal studies.

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