Phytotherapy: A Novel
Approach for Treating
Periodontal Disease
INTRODUCTION
From time immemorial, periodontal diseases have been considered as one of the major health problems affecting humans. Epidemiologic studies have shown that destructive periodontal diseases in the form of periodontitis with significant bone loss have affected mankind in the ancient times also1.
Over the years, periodontal therapy has been influenced by the inclinations of the times, and consequently treatment methodologies have been mod-ified. Our understanding of the etiology and diagnosis of the periodontal diseases is continuously evolving. Periodontal diseases have been linked to anaerobic gram-negative bacteria (Porphyromonas gingivalis, Actinobacillus, Prevotella
and Fusobacterium). Given the incidence of oral disease, increased resistance to
bacteria by antibiotics, adverse effects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for unconventional prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these compounds can alter oral microbiota and have undesirable adverse effects such as vomiting, diarrhoea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives2.
Therapy comes from the Latin word ‘therapia’ originally from Greek therapeia, from therapeuein which means to treat medically. The Latin prefix ‘phyto’ stands for plant and is called photon in Greek. In other words ‘phytotherapy’ can be called as herbal medicine. It is the study of the use of extracts from natural origin as medicines or health promoting agents3.
A key to selecting pharmaceutical plant derivatives for use in medicinal preparations is the global availability4.Plants and naturally derived
prod-ucts have been used to enhance health and medicinal purposes for thou-sands of years. Most herbal supplements have been utilised for centuries based on emperical and testimonial support for their efficacy5. Plant extracts
are widely used as antimicrobial agents. The global need for an alternative prevention, treatment options and products for oral disease arises due to the rise in disease incidence, increased resistance by pathogenic bacteria
Navnita Singh1*, S. Savita2, K. Rithesh3, Shilpa Shivanand1
1 Post Graduate Student, Department of
Periodontology, Rajarajeshwari Dental College and Hospital, Bangalore, India
2 Professor and HOD, Department of
Periodontology,Rajarajeshwari Dental College and Hospital, Bangalore, India
3 Reader, Department of Periodontology,
Rajarajeshwari Dental College and Hospital, Bangalore, India
Address reprint requests to *Dr Navnita Singh, Post Graduate Student, Department of Periodontology, Rajarajeshwari Dental College and Hospital, #14, Ramohalli Cross, Kumbalgodu, Mysore Road, Bangalore, 560074, India
E-mail: [email protected]
Article citation: Singh N, Savita S, Rithesh K, Shivanand S. Phytotherapy: a novel approach for treating periodontal disease.
J Pharm Biomed Sci2016;06(04): 205–210.
Available at www.jpbms.info
Statement of originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Sources of funding: None.
Competing interest / Conflict of interest:
The author(s) have no competing interests for financial support, publication of this research, patents, and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
NLM Title J Pharm Biomed Sci
CODEN JPBSCT
2230-7885 ISSN No
ABSTRACT
Over the years, periodontal therapy has been influenced by the trends of the times, and consequently treatment approaches have been modified. Our understanding of the eti-ology and diagnosis of the periodontal diseases is continuously evolving. Periodontitis caused by various microorganisms is often treated with common antibiotics. But antibiotic resistance is a growing problem. Thus, the global need for an alternative prevention and treatment options arises which is safe, effective and economical. So, researchers are in pursuit for new therapeutic agents from natural sources. There is a long and venerable history of the use of plants to improve dental health and promote oral hygiene. Plants contain phytochemicals such as alkaloids, tannins, essential oils and flavonoids which have pronounced antimicrobial activity. Because of its good antimicrobial activity and safety profile, it proves its use in the treatment of periodontal diseases. This suggests a potentially valuable role for phytotherapy in assisting with the management of this serious disease. The evidence and research which supports such a role for plants (or plant prod-ucts) are reviewed in this study.
KEYWORDS periodontitis, antibiotic resistance, plant extracts
to currently used antibiotics. Thus, phytotherapy may be an answer for alternative treatment option as it is safe, effective and more economical.
HISTORY
There is a long and venerable history of the use of plants to improve dental health and promote oral hygiene. In a review by Lewis and Elvin, they note a quotation cred-ited to the prophet Muhammed: ‘the Siwak (chewing stick) is an implement for the cleansing of teeth and a pleasure to God’. The precise method for the use of this equipment was recorded by the Babylonians in 5,000 BC. The use of chewing sticks persists today among many African and southern Asian communities as well as in isolated areas of tropical America and the southern United States6.In ancient times, plants were
assigned curative powers based on shape or colour7.
The plants used are very carefully selected for properties such as foaminess, hardness, or bitterness and certain species are more popular than others. A great number have related medicinal properties that may be antibac-terial6.The Chinese began using ginseng at least 3,000
years ago, and native Americans used willow bark tea to reduce fever, when most of the ‘civilised world’ was under Roman rule. Each civilisation that has chronicled its progress produced a body of knowledge addressing the use of medicinal plants7.
The oldest written evidence of medicinal plant’s usage for treatment has been found on a Sumerian clay slab from Nagpur, approx. 5,000-year-old. It com-prised 12 recipes for drug preparation referring to over 250 various plants, some of them are alkaloids such as poppy, henbane and mandrake8.The Indian holy books
Vedas mention treatment with plants, which are abun-dant in that country. Numerous spice plants used even today originates from India: nutmeg, pepper, clove, etc9.
The Ebers Papyrus, written circa 1,550 BC, represents a collection of 800 proscriptions referring to 700 plant species and drugs used for therapy such as pomegranate, castor oil plant, aloe, senna, garlic, onion, fig, willow, coriander, juniper, common centaury, etc10.The works
of Hippocrates (459–370 BC) contain 300 medicinal plants classified by physiological action: wormwood and common centaury (Centauriumum bellatum Gilib) were
applied against fever; garlic against intestine parasites; henbane, opium, deadly nightshade and mandrake were used as narcotics; fragrant hellebore and haselwort as emetics; celery, parsley, asparagus, sea onion and garlic as diuretics; oak and pomegranate as adstringents11,12.
Theophrast (371–287 BC) founded botanical sci-ence with his books ‘De Causis Plantarum’—plant eti-ology and ‘De Historia Plantarum’—plant history. In these books, he generated a classification of more than 500 medicinal plants known at that time13,14. Among
others, he referred to cinnamon, iris rhizome, false hellebore, mint, pomegranate, cardamom, fragrant hellebore, monkshood and so forth. In the description
of the plant toxic action, Theophrast underscored the important feature for humans to become accustomed to them by a gradual increase of the doses. Owing to his considerations in botany, he gained the epithet of the ‘father of botany’, given that he has great merits for the classification and description of medicinal plants15,16.
In his work, ‘De re medica’, the renowned medical writer Celsus (25 BC to 50 AD) quoted approximately 250 medicinal plants such as aloe, henbane, poppy, pepper, flax, cinnamon, false hellebore, the star gentian, cardamom, etc17.
PHYTOTHERAPY AND GINGIVITIS
Primary etiology of chronic gingival inflammatory conditions is often found to be bacterial plaque and its byproducts18.Numerous antimicrobial agents have been
and are being tested throughout the world in order to determine which agents are efficacious and safe in pre-venting plaque formation and/or inhibiting the coloni-sation of periodontopathogens within the plaque. Dental plaque is an example of a specialised bacterial biofilm that develops on the surface of teeth, dental restorations, prostheses and implants. A number of methods have been used to evaluate the potential of natural products to reduce or eliminate oral biofilms. Anti-adhesion agents may be preferable than those that are bactericidal as selective pressure leading to resistance and overgrowth of resistant bacteria would be avoided19. Plant extracts
has been used to check for the biofilm. The inhibition of biofilm formation by oral pathogens has been assessed by cell culture plate assays, where bacteria are incubated in the presence or absence of test compounds20,21. After
appropriate incubation, free bacteria are removed from microtiter wells by aspiration; biofilms are stained with crystal violet and the absorbance measured to indi-cate the level of biofilm formation20.In the biofilm
assays, the log bacterial reduction was achieved within 30–60 min after contact with alcoholic extracts and within 60 min with aqueous extracts, Yamanaka et al. conducted a study in which it was concluded that cran-berry polyphenol fraction inhibits biofilm formation, the Arg-gingipain and Lys-gingipain activities of P. gingivalis22.
PHYTOTHERAPY IN PERIODONTITIS
Periodontal disease is a chronic condition which starts with gingival inflammation and progressively develops toward hard and soft tissue destruction and tooth loss23.
The herbs used for treatment of periodontitis are
Acacia catechu wild, aloe vera (Aloe barbadensis miller)
cham-omile, Azadirachta indica, Glycyrrhiza glabra (Liquorice root), Cinnamomum zeylanicum, Allium sativum, Propolis, Mikania lae-vigata, Mikania glomerate, Drosera peltata, Helichrysum italicum, Coptidis rhizome, Piper cubeba, and Syzygium aromaticum. Tea tree
oil (Melaleuca alternifolia) and Cordia verbenacea essential oils
A study done by A Jamil et al. concluded that garlic allicin extract has a potential use for prevention and treat-ment of periodontal disease. In that study, it was found that allicin inhibited growth of all tested bacteria (P. gingivalis, Actinobacillus [Aggregatibacter] actinomycetemcomitans
[Aa], Fusobacterium nucleatum, Streptococcus mutans, Escherichia coli, Streptococcus sobrinus and Actinomyces viscosus). Allicin was
also found to be an effective irreversible inhibitor of the
P. gingivalis proteases. Allicin was also found capable of
killing S. mutans growth in biofilm. Thus, there is
con-siderable evidence that plant extracts, essential oils and purified phytochemicals have the potential to be devel-oped into agents that can be used as preventive or cura-tive agents for periodontal diseases.
ANTIMICROBIAL EVALUATION OF POLYHERBAL EXTRACT IN THE TREATMENT OF PERIODONTITIS
Periodontal disease is marked by bacterial over growth. Important periodontal pathogens are A. actinomycetem-comitans, P. gingivalis, Dialister pneumosintes, Bacteroides forsythus
and Treponema denticola. Other gram-negative anaerobic
rods, some gram-positive bacteria and even enteric rods/pseudomonas may also play roles in the etio- pathogenesis of periodontitis25. Treatment generally
involves mechanical therapy (non-surgical or surgical debridement) in conjunction with antibiotics. A. acti-nomycetemcomitans is one of the most efficient causative
pathogens in this disease.
The minimum inhibitory concentration (MIC) can be used as a quantitative parameter for comparison of antimicrobial activity amongst the extract and standard. In a study done by Neelufar et al., the antimicrobial effi-cacy of the formulated polyherbal extract was tested on
S. mutans, E. coli, Staphylococcus aureus and Proteus vulgaris by Dip
well technique. The results of dip well method showed that the polyherbal extract has good antimicrobial activity26. Another study by Gaetti-Jardim et al. recorded
MIC and MBC values of aqueous and alchoholic extracts of Ficus enormis, Myracrodruon urundeuva and Psidium cattleianum
against four reference strains (A. actinomycetemcomitans, F. nucleatum, P. gingivalis and P. intermedia). Alcoholic and
aqueous extracts from Periplaneta americana, Maytenus ilicifo-lia and P. rotundifoilicifo-lia did not exhibit antimicrobial activity
on planktonic microorganisms, while alcoholic extract from F. enormis was more active than aqueous extract
against planktonic bacteria. MBC was 2 up to 16-fold higher than MIC values27.
ROLE OF FEW KEY PLANTS IN PERIODONTITIS
Aloe vera (Aloe barbadensis miller)
It belongs to the family Asphodelaceae (Liliaceae). It has been used medicinally since the last few thousand years. Reported pharmacological actions of aloe vera include
anti-inflammatory, antibacterial, antioxidant, antiviral and antifungal actions, as well as producing hypoglycemic
effects28.It is extremely helpful in the treatment of
dis-eases like gingivitis and periodontitis29.It reduces
bleed-ing, inflammation and swelling of the gingiva. It is a powerful antiseptic in pockets where normal cleaning is difficult, and its antifungal properties helps greatly in the problem of denture stomatitis, aphthous ulcers, cracked and split corners of the mouth30. It is a
power-ful healing promoter and can be used in the following extractions31. It has been used in root canal treatment
as a sedative dressing and file lubrication during bio-mechanical preparation32. A study was done in which
aloe vera gel was used as a local drug delivery. A sig-nificant reduction in pocket depth when compared to controls and reduction in gingival index, which can be attributed to its anti-inflammatory, antibacterial and wound-healing properties was seen. Thus, subgingival administration of aloe vera gel results in improvement of periodontal condition. Aloe vera can be used as a local drug delivery system because of its various benefits28.
Garlic
Garlic (A. sativum) belongs to the oldest traditional
medicinal plants. Garlic is mentioned in the Bible and the Talmud. Hippocrates, Galen, Pliny the Elder and Dioscorides all mentioned the use of garlic for many conditions, including parasites, respiratory problems, poor digestion and low energy. The anti- infective properties of garlic have long been known to Chinese and Indian civilisations and were first described in Europe by Louis Pasteur33. Garlic is one of the most
extensively researched medicinal plants and its typical odor and antibacterial activity depends on allicin pro-duced by enzymatic activity of allinase (a cysteine sul-phoxidelyase) on alliin after crushing or cutting garlic clove. The antifungal, antiparasitic, antiviral, antimicro-bial, antihypertensive, blood glucose lowering, anti-thrombotic, antimutagenic and antiplatelet properties of garlic have been reported and many of these claims have been scientifically corroborated34. Garlic has an
unusually high concentration of sulphur-containing compounds, and its antibacterial properties are largely due to one particular class of sulphur-containing com-pounds, the thiosulphinates35. Garlic is also alleged to
help regulate blood sugar levels and is an effective way to prevent scurvy, due to its vitamin C content.
Miswak
Miswak chewing sticks are prepared from the roots or twigs of Salvadora persica plants. The periodontal status
of more than 200 adult Sudanese who habitually used either miswak or a toothbrush was compared. Miswak users had significantly lower dental calculus and signs of periodontal disease and a tendency to lower gingival bleeding. Another Sudanese study compared the levels of 25 oral bacteria in miswak and toothbrush users36.
species, were lower in the miswak users. However, miswak use was associated with greater gum recession in one study, which was attributed to their abrasive properties37.
Azadirachta indica (Neem)
Azadirachta indica is well known in India. More than 135
components have been isolated from neem. The main ingredients are nimbin, nimbinin and nimbidin. The neem leaves contain 6-desacetylnimbinene, nimban-diol, nimbolide and quercetin, n-hexacosanol and nonacosane. Beta-sitosterol is present in all parts of the plant38. Neem leaf extracts have anti-arrythmic, anti-
arthritic, antiviral, anti-diabetic and antioxidant. It has anti-ulcer, anti-malarial, antifungal and anti-carcinogenic activities39. A study showed that neem leaf extract is used
to treat dental plaque and gingivitis40.Micro-organisms
found in inflamed gingiva are resistant to tetracycline and penicillin but not to the neem leaf extracts. Also neem leaf extracts cause no allergic reaction in the gin-giva41. The herbal formulation comprising of active
frac-tions from A. indica, Citrullus colocynthis and Cucumis sativus
is useful for preventing dental plaque and ginigivitis in humans and is also used as an antimicrobial agent for preventing disease.
Tulsi
Tulsi extract have been widely used in traditional med-icine and human clinical trial without significant side effects42.The methanol extract and the aqueous extract
of Ocimum sanctum have shown to inhibit acute as well as
chronic inflammations in rats43.Eugenol (l-hydroxy-
2-methoxy-4-allylbenzene), the active constituent present in O. sanctum has been found to be largely responsible
for the anti-inflammatory property of tulsi. A study was done using fluid extract of tulsi leaves for 2% O. sanctum
gel preparation. It demonstrated 97% cyclooxygenase-1 inhibitory activity when assayed at 1,000 μM concen-tration. Hence concluded that 2% tulsi (O. sanctum) gel
can be used as useful adjunct to enhance the results of conventional periodontal therapy44.
Tea tree oil
Tannins are defined as a vegetable substance capable of tanning animal bides to produce leather. This is used as a method to preserve the hide and at a molecular level is affected via the crosslinking by the tannins of hide proteins. Green tea (Camellia sinensis, a rich source of
tan-nins) appears to be much more potent as an antimi-crobial agent than black tea45. In general, antimicrobial
activity decreases when the extent of tea fermentation increases. The antimicrobial activities of extracts of tea products with different extents of fermentation also varied with test organisms. Green tea and the unfer-mented tea exerted the strongest antimicrobial activity
followed by the partially fermented tea products such as Longjing, Tieh-Kuan-Ying, Paochung and Oolong teas. On the other hand, black tea, the completely fermented tea showed the least antimicrobial activity. It was also noted that extracts of Oolong tea prepared in summer exhibited the strongest antimicrobial activity, followed by those prepared in spring, winter and fall. The anti-microbial activity of tea has been attributed to its tannin (polyphenolic) phytochemicals46.
Safflower seed extract (SSE)
The regeneration of the periodontiumis coped up by forming new cementum, periodontal ligament and regrowing the alveolar bone. For occurrence of this regeneration, cells with the capability to synthesise cementum, bone and periodontal ligament needs to occupy the periodontal defect and produce these spe-cialised tissues, as desired47.Recently, safflower seed
extract (Carthamus tinctorius L.), a herbal medicine, has
attracted attention with reference to some of the cellular events like chemotactic response, proliferation and alka-line phosphatase activity of periodontal ligament cells, and osteoblasts to promote the mineralisation process48.
In a study, safflower extract was placed in two-walled infrabony defects. Significant reduction in mean prob-ing pocket depth, gain in mean clinical attachment level and significant mean defect fill of 2.86 ± 0.69 mm was observed30. Regarding the regeneration induced by SSE,
it is supposed to be caused by (a) increasing the chemo-tactic response, proliferation and alkaline phosphatase activity of periodontal ligament cells and osteoblasts49
(b) stimulating the formation of calcification nodules and mRNA expression of bone sialoprotein in periodon-tal ligament and MC3T3 E1 cells50 (c) facilitating the
influx of Ca2+ from the extracellular fluid to the
intra-cellular fluid and thus activates Ca2+ channel of
osteo-blastic cells51.Thus, they concluded that safflower seed
extract may be a novel approach in regeneration of the periodontal tissues.
Grape seed proanthocyanidins extract
Grape seed proanthocyanidins extract (GSPE), a type of flavonoid, is an antioxidant obtained from the seeds of Vitis vinifera52. Its active constituents are
proanthocy-anidins, and these represent a variety of flavan-3-ol, catechin53, which is a scavenging free-radical required
for absorption of calcium. A study was done on 40 Wistar male rats. It was found that GSPE had an effect on mechanical properties associated with rat mandib-ular condyle bone debility. It induced extra bone for-mation in rat mandibular condyles, increase in bone mass and increase in bone strength. The activity of GSPE has been attributed to antioxidants present in its flavan-3- ol or catechin that showed free radical scavenging activity54. It is also well known that free radicals promote
demonstrated that proanthocyanidinis found to inhibit the proteolytic enzyme56, and proteolytic enzyme has an
essential role in initiating bone resorption57. Thus, it is
suggested that GSPE has a potential role in the inhibition of bone resorption.
Pineapple extract
Pineapple is the universal name of Ananas comosus. It
belongs to the member of the family bromeliaceae, which is grown in a number of subtropical and trop-ical countries including, India. It has been widely used as a therapeutic plantin. Several resident cultures and these therapeutic qualities of pineapple are accredited to bromelain, which is an elementary extract from pineapple that contains, along with other compounds, various proteinases. Bromelain has shown to exhibit var-ious fibrinolytic, anti-edematous, anti-thrombotic and anti-inflammatory activities both in vitro and in vivo58.This
qualitative in vitro analysis was conducted to evaluate the
antibacterial efficacy of bromelain tablets (500 mg) on potent periodontal pathogens. Bromelain showed anti-bacterial efficacy against all the isolated strains of both aerobic and anaerobic microorganisms (S. mutans, E. coli, P. gingivalis and A. actenomycemcomitans). Bromelain is one
such agent which has been widely used as anti-inflam-matory and antibacterial drug in the field of medicine and dentistry59.
ADVERSE EFFECTS
Along with multiple advantages of phytotherapy, there are some adverse effects also associated with it. Certain herbs or herbal products may cause direct effects on oral tissues like burning of tongue, numbness and throat/ oral irritations1. Toxicity is usually seen only when
excessive amounts of phytochemicals are ingested. This is rarely encountered because phytotherapy for gingival inflammation usually involves only topical application and systemic administration is not required60.
CONCLUSION
Thus, the need for an alternative treatment options for periodontal diseases which is safe, effective and eco-nomical arises due to the rise in disease incidence and increased resistance by pathogenic bacteria to currently used antibiotics. Natural remedies are more acceptable by the population with a belief that they are safer with fewer side effects than the synthetic ones. Phytotherapy, the most ancient medication, is still useful today because of its benefits.
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