Oral Health Benefits of Neem
Oral Health Benefits of Neem
Oral Health Benefits of Neem
BY
FCDT&T/19/ED/0363
JULY, 2023
1
Oral health benefits of neem
CHAPTER ONE
INTRODUCTION
1.1 Background of the Study
Before the advent of orthodox medicine in Nigeria, local communities relied on herbal
preparations and traditional remedies for the treatment and prevention of various ailments, but the
advent of allopathy decreased the use of herbal remedies (Osuji, 2014). However, in recent times,
there has been a remarkable resurgence in the exploration of natural remedies and traditional
medicinal plants, driven by a growing fascination with their potential health benefits (Ùgwù, 2019;
Nissen, 2022). Among these botanical wonders stands Azadirachta indica, commonly known as
neem, an extraordinary plant with a rich history deeply intertwined with traditional medicine
systems, including Ayurveda, Unani, and Homeopathy (Alzohairy, 2016; Tasanarong et al., 2021).
Revered as "dogon yaro" among the Hausas, “ọgwụ akọm” among the Igbos, and “aforo-oyinbo”
among the Yorubas (Iwu, 2014), neem's versatility has captivated the world, finding application
in culinary, medicinal, and cosmetic realms alike. In India, the medicinal uses of neem are so vast
that it has been described as the most useful traditional medicinal plant (Naveed et al., 2014).
Originating from the Indian subcontinent, A. indica has not only conquered its native land but also
thrived in tropical and subtropical regions globally, earning its reputation as the venerable "wonder
tree" (Yerima et al., 2012). The plant's illustrious reputation stems from its extraordinary healing
properties and diverse applications, particularly in the realm of oral and systemic health. Over the
ages, A. indica has been venerated for its profound effects on oral health, with its leaves and bark
acting as time-honored tools for teeth cleaning and breath-freshening. However, it is not mere
traditions that have guided this practice; rather, it is the intersection of cultural wisdom and cutting-
edge scientific inquiry that reveals the astonishing oral health benefits of this ancient remedy
(Naveed et al., 2014). Neem’s leaves, bark, seeds, and oil have been harnessed for centuries to
treat various conditions, reflecting its profound significance across cultures and time (Muhammad
et al., 2019). Studies have shown that neem extracts have significant antibacterial, anti-
inflammatory, and antioxidant properties that promote oral health (Ùgwù, 2019; Alzohairy, 2016).
Investigations into the therapeutic properties of A. indica have illuminated the potential of its
phytochemicals to combat periodontal disease effectively. The simple act of using neem twigs as
2
Oral health benefits of neem
chewing sticks not only offers gum massage but also thwarts plaque buildup, all while wielding
its inherent antibacterial prowess against oral pathogens (Nwali et al., 2018; Ghonmode et al.,
2013; Heyman et al., 2017). Dentifrices and mouthwashes containing neem extracts prove
effective with fewer side effects than chlorhexidine and can be used as an adjunct therapy in
treating plaque-induced gingivitis due to its polyphenolic content. The antibacterial effects of neem
are probably due to disruption of bacterial cell membrane integrity and inhibition of cell adhesion
of cariogenic bacteria. Neem also exhibits anti-inflammatory properties by inhibiting pro-
inflammatory cytokines and other mediators (Girish & Shankara, 2008). Thus, neem has been
shown to reduce gingival inflammation, further bolstering its position as a formidable ally in the
fight against oral diseases (Patil et al., 2020; Vanka et al., 2001; Wolinsky & Sote, 1984).
Beyond maintaining gingival health, the influence of neem extends to preventing dental caries.
Studies have shown that neem is efficacious against a host of cariogenic bacteria, including
Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus acidophilus, as well as bacteria
implicated in periodontal disease like Aggregatibacter actinomycetemcomitans, Treponema
denticola, and Porphyromonas gingivalis (Kamran et al., 2022; Salam et al., 2014; Ùgwù 2019;
Palombo, 2011). A study by Parashuramaiah and Chanu (2019) revealed that a 5% aqueous
solution of neem extracts was effective against common periodontal pathogens like Prevotella
intermedia and Fusobacterium nucleatum. However, Ùgwù (2019) explained that the ethanol
extracts of neem are more inhibitory than the aqueous extracts because ethanol is a better
extractant. Yerima et al. (2012) noted that neem is also effective against other pathogens like
Pseudomonas aeruginosa, Corynebacterium diphtheriae, and Bacillus species. Similarly, neem's
antifungal properties against Candida albicans hold promise in preventing oral candidiasis,
offering a potent defense against drug-resistant fungal infections affecting the mouth and throat,
especially in HIV patients (Gautam & Garg, 2013; El-Mahmood et al., 2010; Jethawa et al., 2022).
And, perhaps most pleasingly, neem effectively tackles halitosis, eliminating the root causes of
oral malodor while leaving the mouth fresh and revitalized (Sugiarta et al., 2019).
But the remarkable benefits of A. indica do not limit themselves to oral health alone. This
magnificent plant, rich in antioxidants, emerges as a formidable guardian of the body, shielding it
from the ravages of free radicals—molecules that threaten to damage cells and contribute to the
onset of chronic diseases like cancer, heart disease, and Alzheimer's (Sandhir et al., 2021).
3
Oral health benefits of neem
Additionally, neem's anti-inflammatory prowess holds the potential to quell the flames of
inflammation throughout the body, a pivotal factor in numerous chronic conditions, including
arthritis, diabetes, and heart disease (Tasanarong et al., 2021). The plant is a favorite malaria
remedy in Africa and has been acknowledged as effective in malarial attacks for which allopathic
antimalarial drugs were found ineffective either due to the presence of resistant Plasmodium strains
or due to acquired tolerance from repeated dosing with conventional drugs. Its dried flowers are
used as tonic and stomachic and are topically applied to treat chronic eczema and as a fly repellant
(Iwu, 2014). A dilute infusion of the bark is administered as antipyretic, and a bitter. There is also
limited use of the aqueous decoction of the root as an anti-helminthic agent. The seed oil is widely
used as an ingredient in the preparation of remedies for hemorrhoids, jaundice, and peptic ulcers.
In Edo State, Nigeria, neem fruit juice is said to be useful in the treatment of boils, syphilitic sores,
skin diseases, glandular swellings, jaundice, and peptic ulcers. The fruit is also used as a laxative
and for the treatment of urinary diseases, leprosy, and intestinal worm infestation (Iwu, 2014).
This seminar paper aims to explore the oral health benefits of the phytochemicals found in A.
indica. Through a systematic review of scientific studies and traditional knowledge, it elucidates
the remarkable therapeutic properties of neem in promoting oral hygiene and preventing various
oral health issues, as well as its contributions to overall systemic health.
4
Oral health benefits of neem
CHAPTER TWO
LITERATURE REVIEW
The World Health Organization (WHO, 2012) defines oral health as a state of being free from
mouth and facial pain, oral and throat cancer, oral infection and sores, periodontal disease, tooth
decay, tooth loss, and other diseases and disorders that limit an individual’s capacity in biting,
chewing, smiling, speaking, and psychosocial wellbeing. The World Dental Federation (FDI)
similarly defines oral health as multifaceted including the ability to speak, smile, smell, taste,
touch, chew, swallow and convey a range of emotions through facial expressions with confidence
and without pain, discomfort, and disease of the craniofacial complex (Glick et al., 2016). Neem
has demonstrated oral health benefits related to these definitions. Studies have shown that different
neem parts exhibit antimicrobial, anti-inflammatory, and immuno-stimulant properties that can
help prevent periodontal disease, oral ulcers, and oral infections that cause pain and limit facial
expression and function. Its antiplaque properties also inhibit cavities and tooth decay preserving
tooth structure and function.
Azadirachta indica is a fast-growing evergreen tree belonging to the mahogany family Meliaceae
(Alexander & Straub-Bruce, 2014). It can reach heights of 20-23 meters with a straight trunk
diameter of around 4-5 feet (National Research Council, 1992). The leaves are pinnately
compound, with each leaf containing 5-15 leaflets in an alternate arrangement (Biswas et al.,
2002). The flowers are small and white, arranged in clusters, which develop into olive-shaped
fruits containing one seed each (Kumar and Navaratnam, 2013). The fruits turn from green to
golden yellow when ripe during June-August (Schmutterer, 2005).
Neem is native to the Indian subcontinent and grows abundantly in tropical and subtropical regions
of India, Bangladesh, Pakistan, and Nepal (Schmutterer, 2005). The plant was introduced and is
now naturalized in Africa. It is widely cultivated in West and Central Africa as an ornamental
plant. It is drought-resistant and therefore grows well in the arid parts of the continents (Iwu, 2014).
It thrives in warm, dry conditions with an annual rainfall of 400-1200 mm and can tolerate high
5
Oral health benefits of neem
temperatures up to 50o C (Subapriya & Nagini, 2005). Neem has an extensive root system that
helps it flourish even in drought conditions (Koul et al., 1990). The tree can live for over 200 years
(National Research Council, 1992).
Note. Adapted from “Therapeutics role of Azadiratchta indica (neem) and their active constituents
in disease prevention and treatment”, by M. A. Alzohairy, 2016, Evidence-Based Complementary
and Alternative Medicine, (p. 2). Copyright (2016) by Mohammed A. Alzohairy.
2.3 Vital Phytochemical Compositions of A. indica
Azadirachta indica contains a diverse array of biologically active phytochemical constituents that
contribute to its therapeutic properties. The most important constituents are the liminoids,
specifically azadirachtin, which demonstrates insecticidal, antifeedant, and growth-regulating
activities (Biswas et al., 2002). Other key liminoids found in neem include salannin, nimbin,
nimbidin, and gedunin (National Research Council, 1992). A. indica leaves are rich in flavonoids
such as quercetin and kaempferol, which have antioxidant, anti-inflammatory, and antimicrobial
effects (Subapriya & Nagini, 2005). The seeds also contain high levels of triterpenoids like nimbiol
and fatty acids such as tiglic acid (Alzohairy, 2016). Polysaccharides and polyphenols isolated
from the gum and barks add to the overall bioactive profile of neem (Iwu, 2014). A. indica is a
treasure trove of diverse phytochemical compounds that work synergistically to produce the
observed pharmacologic activities (Iwu, 2014). Although about 135 compounds have been
extracted from different parts of neem only a few compounds’ biological activity has been studied
extensively (Tanguturi et al., 2020). The following are some of its biologically active compounds:
6
Oral health benefits of neem
2.3.1 Nimbidin
Nimbidin is extracted from neem seed oil and demonstrates anti-inflammatory, antipyretic,
hypoglycemic, antiulcer, antibacterial, and antifungal properties (Tanguturi et al., 2020). It inhibits
the production of inflammatory mediators like nitric oxide and prostaglandin E2 in macrophages
and helps manage fever, gastric ulcers, infections, and blood sugar levels (Khosla et al., 2000).
2.3.2 Azadirachtin
This is a limonoid found in neem seeds. It exhibits anti-inflammatory and antimalarial activities
by free radical scavenging and inhibiting the growth of Plasmodium parasites (Iwu, 2014).
2.3.3 Nimbolide
2.3.4 Gedunin
Isolated from neem seed oil, it shows anti-cancer properties by inhibiting the proliferation of
cancer cells from various tissues. It has antifungal and antimalarial activities (Parida et al., 2002).
2.3.5 Mahmoodin
2.3.6 Tannins
Tannins from neem inhibit inflammation by suppressing oxidative bursts in neutrophils (Tanguturi
et al., 2020).
2.3.7 Diterpenoids
7
Oral health benefits of neem
Although neem’s phytochemicals have therapeutic implications in the prevention and treatment of
diseases, the exact molecular mechanism is not clearly understood. It is believed that the plant’s
therapeutic role is due to its rich source of antioxidants and other valuable active compounds
(Alzohairy, 2016). Neem exhibits a wide range of pharmacological activities due to its diverse
phytochemical constituents. The key bioactive compounds are azadirachtin, gedunin, nimbidin and
quercetin which contribute to the analgesic, anti-inflammatory, antimicrobial, antimalarial, and
antioxidant properties (Koul et al., 1990; Subapriya & Nagini, 2005).
constituents working via different mechanisms such as enzyme inhibition, anti-oxidation, anti-
inflammation, and direct antimicrobial action against various pathogens (Schmutterer, 2005).
8
Oral health benefits of neem
These multifaceted mechanisms underline neem’s diverse pharmacological and therapeutic utility
Azadirachta indica possesses a wide range of health benefits due to its diverse phytochemical
constituents. The key bioactive components like azadirachtin, nimbolide, nimbidin and
analgesic, anti-inflammatory, and antidiabetic properties traditionally used in Africa and Asia
(Biswas et al., 2002). The leaves, flowers, and fruits are used to treat fever, malaria, stomach pain,
Neem demonstrates antioxidant, anticancer, and immunomodulatory effects. The leaves and bark
possess free radical scavenging and antioxidant activity (Subapriya & Nagini, 2005). Gedunin and
nimbolide inhibit cancer growth by modulating cell signaling pathways and inducing apoptosis
(Alzohairy, 2016). Neem also stimulates immune cell proliferation to mediate anti-inflammatory
and antitumor responses (Biswas et al., 2002). Neem exhibits a broad spectrum of pharmacological
activities and has ethnomedical importance owing to its wide range of health-promoting
9
Oral health benefits of neem
Fig. 1: Therapeutic activities of bioactive components of neem and their mechanism of action
Note. Adapted from “Azadirachta indica (neem): An ancient Indian boon to the contemporary
world of dentistry”, by S. C. Tanguturi et al., 2020, In D. N. Chauhan, P. R. Singh, K. Shah, & N.
S. Chauhan (Eds.), Natural Oral Care in Dental Therapy (p. 316). John Wiley. Copyright (2020)
by Durgesh Nandini Chauhan, Prabhu Raj Singh, Kamal Shah, and Nagendra Singh Chauhan.
Components like nimbidin suppress neutrophils and macrophages to reduce inflammation. Neem
leaf and seed extracts exhibit anti-inflammatory properties but are less potent than conventional
drugs like dexamethasone (Ilango et al., 2013). A. indica’s seed oil also demonstrates dose-
dependent analgesic effects in rats (Alzohairy, 2016).
10
Oral health benefits of neem
Neem contains antioxidants like azadirachtin and nimbolide that scavenge free radicals. Studies
show neem leaf and bark extracts have significant antioxidant capacities (Ghimeray et al., 2009).
Neem leaf extracts increase tumor suppressor proteins like p53 and pTEN to inhibit cancer cell
proliferation. The limonoid, nimbolide induces apoptosis and prevents cancer progression
(Arumugam et al., 2014).
Neem extracts from the leaves, seeds, and bark demonstrate antibacterial activity against both
gram-positive and negative bacteria like Pseudomonas aeruginosa, Proteus mirabilis,
Staphylococcus aureus, and Enterococcus faecalis (Reddy et al., 2013; Yerima et al., 2012). Neem
bark extracts also exhibit antiviral effects against herpes simplex virus and coxsackie virus (Tiwari
et al., 2010). Udeinya et al. (2008) observed that neem leaf extracts showed antiretroviral activity
with a mechanism of action that may involve the inhibition of cytoadhesion. Additionally, neem
leaf extracts inhibit the growth of fungi like Aspergillus fumigates, and Candida albicans
(Tanguturi et al., 2020).
A study by Maan et al. (2017) on mice showed that neem extracts accelerate incision and excision
wound closure and increase the tensile strength of healing skin tissues compared to the control.
11
Oral health benefits of neem
Neem continues to be used in various forms in traditional medicine practices as well as modern
wellness applications:
i. Chewing sticks: Fresh neem twigs are still used as chewing sticks for teeth cleaning
and oral hygiene in many parts of Asia and Africa (Iwu, 2014; Vanka et al., 2001).
ii. Dentifrices: Neem-based toothpowders and pastes containing neem leaf extracts are
popular herbal dentifrices (Chava et al., 2012).
iii. Mouthwashes: Neem leaf extracts are formulated into oral rinses and mouthwashes
for antibacterial, anti-inflammatory benefits (Vanka et al., 2001).
iv. Poultices: Crushed neem leaves are used to make medicinal poultices that are applied
to treat gum infections and mouth ulcers (Iwu, 2014).
v. Cosmetics: Neem seed oil extracts are used in natural soaps and creams for skin
benefits (Subapriya & Nagini, 2005).
vi. Culinary: Young neem leaves are added to soups, curries, and chutneys in Indian
cuisine (Alzohairy, 2016).
vii. Agrochemicals: Neem seed extracts are used as natural pesticides, insect repellents,
and fertilizers (Schmutterer, 2005).
Neem tree extracts have traditionally been used in dentistry for their anti-inflammatory and
antimicrobial properties. Its bioactive components like azadirachtin, nimbidin, and gedunin exhibit
antibacterial effects against oral pathogens involved in dental caries and periodontal diseases and
inhibit biofilm formation (Pai et al., 2004; Chava et al., 2012). Neem extracts demonstrate anti-
plaque activity and control plaque-induced gingivitis when used as a mouthwash, dentifrice, or
chewing sticks (Pai et al., 2004; Vanka et al., 2001). Polyphenols and limonoids also exhibit anti-
inflammatory effects to reduce gingival inflammation and periodontitis (Chava et al., 2012).
Furthermore, neem protects against oral cancers through its antioxidant, antimutagenic, and
chemopreventive effects mediated by compounds like azadirachtin, nimbolide, and polyphenols
(Paul et al., 2011). Thus, Azadirachta indica phytochemicals demonstrate potential therapeutic
effects for maintaining oral health owing to their antimicrobial, anti-inflammatory, and anticancer
properties. Below is a summary of Neem’s applications in dentistry:
12
Oral health benefits of neem
2.6.2 Endodontics
Neem extracts exhibit antibacterial efficacy against endodontic pathogens like E. faecalis and C.
albicans. Neem is as effective as tulsi, chlorhexidine, and other herbal irrigants in disinfecting
infected root canals (Chandrappa et al., 2015; Babaji et al., 2016).
Neem demonstrates antimicrobial effects against oral microbes involved in dental caries,
gingivitis, and candidiasis. It also reverses initial carious lesions and inhibits caries-causing
bacteria like S. mutans (Vanka et al., 2001). However, neem-fluoride combinations reduce dental
erosion better than neem alone (Sales Peres et al., 2013).
Neem phytochemicals like nimbolide and azadirachtin demonstrate chemopreventive and anti-
proliferative effects against oral cancer cells. They modulate pathways involved in cell
proliferation, angiogenesis, and apoptosis (Paul et al., 2011).
2.6.5 Indications
Neem is indicated for the treatment and prevention of numerous dental diseases and conditions
including angular cheilitis, aphthous stomatitis, black hairy tongue, Bisphosphate-Related
Osteonecrosis of the Jaw (BROJ/ONJ), oral candidiasis, dental caries, cysts/tumors, denture
stomatitis, gingivitis, glossitis, halitosis, herpes, Human papillomavirus (HPV) infection,
hyperplasia, Kawasaki disease, meth mouth, necrotizing ulcerative gingivitis (NUG), oral
piercings, pericoronitis, periodontitis, tooth sensitivity, sinusitis, sores, ulcers, part of a mouth rinse
for post-extraction/scaling/filling/ prosthetic fitting/adjustment, etc. (Alexander & Straub-Bruce,
2014).
13
Oral health benefits of neem
Prolonged internal use of neem can affect fecundity. Azadirachtin, nimbolide, saponins,
polysaccharides, and flavonoids demonstrate spermicidal properties that can affect male fertility
though this effect is reversible upon discontinuation (Deshpande et al., 1980). Neem is
contraindicated in gestation and lactation (Alexander & Straub-Bruce, 2014) because the safety of
neem in human pregnancy has not been established. Neem extracts can terminate early pregnancy
and inhibit embryo implantation in the uterus of animals when given orally (Mukherjee et al.,
1999). Additionally, it disrupts the estrus cycle and affects sperm parameters and fertility in males
and females. Active compounds of neem like azadirachtin and nimbolide may get excreted in
breast milk and transfer to the nursing infant upon maternal consumption (Prakash et al., 1988).
2.7 Traditional Use of Neem in Oral Health: A Historical and Cultural Exploration
Azadirachta indica has played a vital role in traditional medicine systems for centuries, especially
in regions where it is native like the Indian subcontinent, and in places where it is now naturalized
such as West Africa (Ùgwù, 2019; Oliver-Bever, 1986). Neem's versatility has made it an essential
part of folk remedies, particularly in oral care practices. This section delves into historical and
cultural references, tracing neem's profound impact on oral health through tooth cleaning, gum
massage, and breath freshening techniques in traditional medicine systems.
Neem has been used for dental and oral hygiene in West Africa for centuries as part of folk
medicine. References to neem twigs as toothbrushes called “chewing sticks” date back to antiquity,
with references found in texts from traditional medicine systems such as Ayurveda, Siddha, and
Unani (Uddin et al., 2018).
Neem holds cultural significance in Nigeria, where it is considered a valuable resource in daily
life. Beyond its medicinal uses, neem is also employed for other purposes, such as natural insect
repellents and cosmetic products (Iwu, 2014). Despite advancements in modern healthcare, neem’s
importance in Nigerian culture remains strong. Many communities continue to use neem in
traditional healing practices, highlighting its enduring value in promoting well-being (Iwu, 2014).
14
Oral health benefits of neem
The World Health Organization recognizes chewing sticks like neem as part of the traditional oral
self-care system in West African cultures (Petersen, 2008). Neem twigs are culturally significant
for oral hygiene among various ethnic groups in Nigeria (Sote, 1987), especially among the Hausa
and Fulani where it is used to treat dentalgia (Enwonwu & Anyanwụ, 1985). Neem’s use in Nigeria
can be traced back to ancient times when indigenous communities discovered its medicinal
properties and integrated it into their healing practices. The leaves, bark, seeds, and oil of neem
were utilized to address various health issues, including oral care, skin conditions, and digestive
problems (Nwali et al., 2018).
In Nigerian traditional medicine, neem has been utilized for maintaining oral health. Chewing on
neem twigs has been a common practice to clean teeth and freshen breath. The twigs’ natural
antibacterial properties and fibrous texture aid in removing plaque and promoting oral hygiene.
Young neem twigs are frayed at one end to make bristles for brushing. They also have
antimicrobial properties beneficial for cavity prevention (Sote, 1987).
Chewed neem sticks or bark extracts are rubbed on gums for anti-inflammatory and healing effects
against gingivitis and periodontal disease (Patel & Venkatakrishna-Bhatt, 1988).
Neem products like bark extracts, oils, and leaves are used as breath fresheners in Nigeria and
applied topically or as rinses (Oliver-Bever, 1986). Neem has an extensive ethnomedical history
and cultural relevance for oral hygiene in West Africa owing to its tooth cleaning, gum healing,
and breath freshening properties. Neem’s historical and cultural exploration in Nigeria reveals its
deep-rooted significance in traditional medicine and daily life. The practice of using neem for oral
care and other purposes continues to be an integral part of Nigerian communities, underscoring its
enduring relevance and potential as a valuable natural remedy.
Neem has a long history of traditional use for oral health in many cultures, but modern scientific
research is now validating its benefits through rigorous study. There is tremendous scope for
15
Oral health benefits of neem
integrating traditional knowledge about neem’s healing properties with evidence-based research
to fully explore and substantiate its therapeutic potential (Patel & Venkatakrishna-Bhatt, 1988).
Collaborations between traditional medicine practitioners and dental scientists can uncover the
active phytochemicals underlying observed ethnomedical effects, elucidate pharmacological
mechanisms of action, and examine the bioactivity of extracts using contemporary laboratory
techniques (Pai et al., 2004). The rich trove of empirical indigenous wisdom can guide hypothesis
formulation and direct investigative efforts to isolate bioactive neem formulations for oral
applications (Oliver-Bever, 1986). Integrating science and tradition thus leverages the strengths of
both systems – cultural familiarity and holistic insights of traditional medicine complemented by
the analytical rigor and standardization of modern science (Pai et al., 2004). This interdisciplinary
approach can provide the ideal framework to harness neem’s multifaceted applications for oral
health promotion based on bio-scientific evidence corroborated by traditional practices.
Neem has demonstrated extensive therapeutic potential across various dental applications ranging
from oral hygiene to periodontal disease and even oral cancer management. However, there are
challenges to be addressed before neem-based formulations can be broadly adopted into clinical
dentistry. Standardization and quality control of bioactive extracts are critical to ensure efficacy
and safety (Dhingra & Vandana, 2017). More well-designed human clinical trials are needed to
conclusively establish efficacy alongside identifying optimal therapeutic concentrations and
dosages (Dhingra & Vandana, 2017). Potential toxicity and drug interactions must be investigated
especially with long-term use (Dhingra & Vandana, 2017). Despite these limitations, neem holds
immense promise as a versatile, efficacious, and safe phytomedicine for oral health promotion. Its
multifaceted antimicrobial, anti-inflammatory, and anticancer effects can be leveraged to develop
novel dental therapeutics. With advances in biomedical and pharmaceutical research, the
challenges of neem’s clinical translation can be effectively surmounted to realize its full potential
in preventive and restorative dentistry.
16
Oral health benefits of neem
CHAPTER THREE
Azadirachta indica, has a time-honored status in traditional medicine systems due to its
multifaceted therapeutic utility. Modern research has substantiated its diverse pharmacological
properties ranging from antimicrobial, anti-inflammatory, immunomodulatory, antioxidant,
chemopreventive, antimalarial, and antidiabetic effects. Neem is a rich source of bioactive
phytochemicals like azadirachtin, nimbolide, nimbidin, gedunin, and polyphenols which mediate
these observed bioactivities through a multitude of molecular mechanisms. Extensive studies
underscore Neem's applications for oral health promotion and treatment ranging from dental caries
and plaque prevention to managing gingivitis, periodontitis, and oral malignancies. Neem thus
holds tremendous potential as a versatile, safe, and efficacious phytomedicine for integrative
dentistry. However, more rigorous clinical investigations are warranted to standardize therapeutic
formulations, determine optimal dosages, assess toxicity with long-term use, and examine
interactions with conventional drugs. Evidence-based research substantiated by traditional
knowledge can provide the framework for successfully harnessing the promising multidimensional
utilities of neem for modern dental practice.
3.2 Recommendation
Based on the extensive literature reviewed, Azadirachta indica has demonstrated tremendous
potential for multifaceted oral health applications ranging from dental hygiene to managing
periodontal disease, caries prevention, and even oral cancer. However, several aspects need further
investigation before neem formulations can be extensively incorporated into clinical practice.
i. More rigorous clinical studies on diverse patient populations are needed to conclusively
establish optimal therapeutic dosages, safety with long-term use, and potential
interactions with conventional medications.
ii. Pharmaceutical standardization and quality control protocols for bioactive neem
extracts must be developed to ensure consistent efficacy and potency.
iii. Toxicity concerns especially with pregnancy and risk groups need thorough evaluation
through preclinical studies before large-scale human trials.
17
Oral health benefits of neem
18
Oral health benefits of neem
References
Alexander, L. M., & Straub-Bruce, L.A. (2014). Dental herbalism: Natural therapies for the
mouth. Healing Arts Press.
Alzohairy, M. A. (2016). Therapeutics role of Azadiratchta indica (neem) and their active
constituents in disease prevention and treatment. Evidence-Based Complementary and
Alternative Medicine, 2016(1), 1-11. http://dx.doi.org/10.1155/2016/7382506
Arumugam, A., Agullo, P., Boopalan, T., Nandy, S., Lopez, R., Gutierrez, C., Narayan, M., &
Rajkumar, L. (2014). Neem leaf extracts inhibit mammary carcinogenesis by altering cell
proliferation, apoptosis, and angiogenesis. Cancer Biology & Therapy, 15(1), 26–34.
https://doi.org/10.4161/cbt.26604
Babaji, P., Jagtap, K., Lau, H., Bansal, N., Thajuraj, S., & Sondhi, P. (2016). Comparative
evaluation of antimicrobial effect of herbal root canal irrigants (Morinda citrifolia,
Azadirachta indica, Aloe vera) with sodium hypochlorite: An in vitro study. Journal of
International Society of Preventive & Community Dentistry, 6(3), 196–199.
https://doi.org/10.4103/2231-0762.183104
Biswas, K., Chattopadhyay, I., Banerjee, R. K., & Bandyopadhyay, U. (2002). Biological
activities and medicinal properties of neem (Azadirachta indica). Current Science, 82(11),
1336-1345. http://www.jstor.org/stabl/234106000
Chandrappa, P. M., Dupper, A., Tripathi, P., Arroju, R., Sharma, P., & Sulochana, K. (2015).
Antimicrobial activity of herbal medicines (tulsi extracts, neem extracts) and chlorhexidine
against Enterococcus faecalis in Endodontics: An in vitro study. Journal of International
Society of Preventive & Community Dentistry, 5(2), S89–S92. https://doi.org/10.4103/2231-
0762.172952
Chava, V. R., Manjunath, S. M., Rajanikanth, A. V., & Sridevi, N. (2012). The efficacy of neem
extracts on four microorganisms responsible for causing dental caries viz Streptococcus
mutans, Streptococcus salivarius, Streptococcus mitis and Streptococcus sanguis: An in
vitro study. Journal of Contemporary Dental Practice, 13(6), 769-772.
Deshpande, V. Y., Mendulkar, K. N., & Sadre, N. L. (1980). Male antifertility activity of
Azadirachta indica in mice. Journal of Postgraduate Medicine, 26(3), 167–170.
Dhingra, K., & Vandana, K. L. (2017). Effectiveness of Azadirachta indica (Neem) mouthrinse
in plaque and gingivitis control: A systematic review. International Journal of Dental
Hygiene, 15(4), 4-15. https://doi.org/10.1111/idh.12191
El-Mahmood, A. M., Ogbonna, O. B., & Raji, M. (2010). The antibacterial activity of
Azadarichta indica (neem) seed extracts against bacterial pathogens associated with eye and
ear infections. Journal of Medicinal Plants Research, 4(14), 1414-1421.
https://doi.org/10.5897/JMPR09.169
Enwonwu, C. O. & Anyanwụ, R. C. (1985). The chewing stick in oral health care. World Health
Forum, 6(1), 232-234.
19
Oral health benefits of neem
20
Oral health benefits of neem
Kasilo, O. M. J., Wambebe, C., Nikiemia, J-B., Nabyonga-Orem, J. (2019). Towards universal
health coverage: Advancing the development and use of traditional medicines in Africa.
BMJ Global Health, 4(9), e001517. https://doi.or/10.1136bmjgh-2019-001517
Khosla, P., Bhanwra, S., Singh, J., Seth, S., & Srivastava, R. K. (2000). A study of
hypoglycaemic effects of Azadirachta indica (Neem) in normal and alloxan diabetic rabbits.
Indian Journal of Physiology and Pharmacology, 44(1), 69–74.
Koul, O., Isman, M.B., & Ketkar, C. M. (1990). Properties and uses of neem, Azadirachta
indica. Canadian Journal of Botany, 68(1), 1-11. https://doi.org/10.1139/b90-001
Kumar, V. S., & Navaratnam, V. (2013). Neem (Azadirachta indica): Prehistory to
contemporary medicinal uses to humankind. Asian Pacific Journal of Tropical Biomedicine,
3(7), 505-514. https://doi.org/10.1016/S2221-1691(13)60105-7
Kumar, V. P., Chauhan, N. S., Padh, H., & Rajani, M. (2006). Search for antibacterial and
antifungal agents from selected Indian medicinal plants. Journal of
Ethnopharmacology, 107(2), 182–188. https://doi.org/10.1016/j.jep.2006.03.013
Maan, P., Yadav, K. S., & Yadav, N. P. (2017). Wound Healing Activity of Azadirachta
indica A. Juss Stem Bark in Mice. Pharmacognosy Magazine, 13(2), S316–S320.
https://doi.org/10.4103/0973-1296.210163
Morgan, E. D. & Wilson, I. D. (1999). Miscellaneous natural products including marine natural
products, pheromones, plant hormones, and aspects of ecology. In D. Barton, K. Nakanishi,
& O. Meth-Cohn (Eds.), Comprehensive Natural Products in Chemistry (pp. 1-18).
Elsevier.
Muhammad, A., Lawan, I. M., Abubakar, A., & Dangora, I. I. (2019). Antimicrobial Activity of
A. indica (Neem) Leave Extracts Against Some Clinical Isolates. Dutse Journal of Pure and
Applied Sciences (DUJOPAS), 5(1b), 97-104.
Mukherjee, S., Garg, S., & Talwar, G. P. (1999). Early post implantation contraceptive effects of
a purified fraction of neem (Azadirachta indica) seeds, given orally in rats: Possible
mechanisms involved. Journal of Ethnopharmacology, 67(3), 287–296.
https://doi.org/10.1016/s0378-8741(99)00068-9
National Research Council (US) Panel on Neem. (1992). Neem: A tree for solving global
problems. National Academies Press (US).
Naveed, N., Murthykumar, K., Soundarajan, S., Srinivasan, S. (2014). The use of neem in oral
health. Research Journal of Pharmacy and Technology, 7(9), 1060-1064.
Nissen, M. (2022). Factors responsible for increased use of herbal medicines and self-
medication. Advances in Pharmacoepidemiology and Drug Safety, 11(3), 1-2.
Nwali, O. N., Idoko, A. 1., Okolie, J. E., Ezeh, E., Ugwudike, P. O., Rita, O. N., Ezenwali, M.
O., Odo, I. A., Ani, P. N., & Okolie, S. O. (2018). Comparative analysis of the
phytochemical compositions of leaf, stem bark, and root of Azadirachta indica (neem).
21
Oral health benefits of neem
22
Oral health benefits of neem
Sandhir, R., Khurana, M., Kumar, S. (2021). Potential benefits of phytochemicals from A. indica
against neurological disorders. Neurochemistry International, 146, 105023.
https://doi.org10.10.1016/j.neuint.2021.105023
Salam, R., Khokon, J. U., Baidya, S., & Mussa, M. T. (2014). Effect of neem and betel leaf
against oral bacteria. International Journal of Natural and Social Sciences, 1(2014), 52-57.
Sales-Peres, A. C., Marsicano, J. A., Garcia, R. P., Forim, M. R., Silva, M. F., & Sales-Peres, S.
H. (2013). Effect of natural gel product on bovine dentin erosion in vitro. Journal of
Applied Oral Science, 21(6), 597–600. https://doi.org/10.1590/1679-775720130242
Schmutterer, H. (2005). The neem tree: Source of unique natural products for integrated pest
management, medicine, industry, and other purposes. Wiley-Blackwell.
Sote E. O. (1987). The relative effectiveness of chewing sticks and toothbrushes on plaque
removal. African Dental Journal: Official Publication of the Federation of African Dental
Associations = Journal Dentaire Africain, 1(2), 48–53.
Subapriya, R., & Nagini, S. (2005). Medicinal properties of neem leaves: A review. Current
Medicinal Chemistry, Anti-cancer Agents, 5(20). 149-156.
https://doi.org/10.2174/1568011053174828
Sugiarta, A. P., Lessang, R., & Natalina, N. (2019). Effect of herbal toothpaste containing neem
leaves extracts (A. indica) against gingivitis: A clinical study. International Journal of
Applied Pharmaceutics, 11(1), 1-3. https://doi.org/10.22159/ijap.2019.v11s1.ar173
Tanguturi, S. C., Gunupati, S., & Nagarakanti, S. (2020). Azadirachta indica (neem): An ancient
Indian boon to the contemporary world of dentistry. In D. N. Chauhan, P. R. Singh, K.
Shah, & N. S. Chauhan (Eds.), Natural Oral Care in Dental Therapy (pp. 313-328). John
Wiley & Sons.
Tasanarong, P., Patntirapong, S., & Aupaphong, V. (2021). The inhibitory effect of a novel neem
pastes against cariogenic bacteria. Journal of Clinical and Experimental Dentistry, 13(11),
e1083-e1088. https://doi.org/10.4317/jced.58781
Tiwari, V., Darmani, N. A., Yue, B. Y., & Shukla, D. (2010). In vitro antiviral activity of neem
(Azardirachta indica L.) bark extracts against herpes simplex virus type-1 infection.
Phytotherapy Research, 24(8), 1132–1140. https://doi.org/10.1002/ptr.3085
Uddin, S., Nuri, Z. N., Alam, K., & Hoq, O. (2018). Neem (Azadirachta indica) in health care: A
review. International Journal of Unani and Integrative Medicine, 2(2), 81-87.
Udeinya, I. J., Mbah, A. U., Chijioke, C. P., & Shu, E. N. (2004). An antimalarial extract from
neem leaves is antiretroviral. Transactions of the Royal Society of Tropical Medicine and
Hygiene, 98(7), 435–437. https://doi.org/10.1016/j.trstmh.2003.10.016
Ùgwù, C. C. (2019). Antimicrobial activity of Azadirachta indica (neem) leaf extracts on some
bacteria. International Journal of Current Microbiology and Applied Sciences, 8(7), 431-
437. https://doi.org/10.20546/ijcmas.2019.807.053
23
Oral health benefits of neem
Vanka, A., Tandon, S., Rao, S. R., Udupa, N., & ramkumar, P. (2001). The effect of indigenous
neem Azadirachta indica [correction of (Adirachta indica)] mouthwash on Streptococcus
mutans and lactobacilli growth. Indian Journal of Dental Research: Official Publication of
Indian Society for Dental Research, 12(3), 133-144.
Wolinsky, L. E., & Sote, E. O. (1984). Isolation of natural plaque-inhibiting substances from
‘Nigerian chewing sticks.’ Caries Research, 18(3), 216-225.
https://doi.org/10.1159/000260768
Yerima, M. B., Jodi, S. M., Oyinbo, K., Maishanu, H. M., Farouq, A. A., Junaidu, A. U., Al-
Mustapha, M. N., & Shinkafi, A. L. (2012). Effect of neem extracts (A. indica) on bacteria
isolated from the adult mouth. Nigerian Journal of Basic and Applied Science, 20(1), 64-67.
24