Phytotherapeutics in the management of periodontal disease - A review

Prakash G Pai, MM Dayakar, Anjali R Nath, G Ashwini
Department of Periodontology, K V G Dental College and Hospital, Dakshina Kannada, Karnataka, India

Date of Web Publication

9-Jul-2019

Correspondence Address:
Dr. M M Dayakar
Department of Periodontology, K V G Dental College and Hospital, Sullia, Dakshina Kannada, Karnataka
India

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DOI: 10.4103/srmjrds.srmjrds_41_18

Abstract

Phytotherapy is the usage of herbal species with medicinal properties for the management of various diseases. Gingivitis and periodontitis are diseases that involve the role of both the bacteria and the host immune response. Over the years, various researches have shown the importance of herbal products in the management of periodontal diseases. Plants have phytochemicals such as alkaloids, essential oils, flavonoids, and tannins that have strong antimicrobial activity and used as an anti-inflammatory, antibiotic, analgesic, and antioxidative agents. The aim of this review is to provide the current literature to validate the traditional use of medicinal plants in the management of periodontal diseases.

Keywords: Antibacterial, antioxidant, host response, immunomodulatory, periodontitis

How to cite this article: Pai PG, Dayakar M M, Nath AR, Ashwini G. Phytotherapeutics in the management of periodontal disease - A review. SRM J Res Dent Sci 2019;10:82-9

How to cite this URL: Pai PG, Dayakar M M, Nath AR, Ashwini G. Phytotherapeutics in the management of periodontal disease - A review. SRM J Res Dent Sci [serial online] 2019 [cited 2019 Jul 10];10:82-9. Available from: http://www.srmjrds.in/text.asp?2019/10/2/82/262382

Introduction

Our understanding of the etiology, diagnosis, and management of the periodontal diseases is continuously evolving.^[1] The primary etiological factor causing periodontal diseases are bacterial plaque and its byproducts. The severity of periodontal disease and its association between poor oral hygiene, dental plaque is also well-established.^[2] As the researchers are seeking alternatives to conventional treatment, they have found that bacteria that lead to periodontal diseases can be suppressed by phytotherapeutic agents. Hence, there is a pronounced interest in the development of phytotherapeutic agents for the periodontal therapy. The word “phytotherapy” is a Latin term. In the word phytotherapy, the prefix “phyto” means plant and “therapy” means healing and curing. In other words, “phytotherapy” means treatment with herbal medicine. Herbal products have been used in folk medicine since ancient times, in both eastern and western medical traditions. Over the past decades, pharmaceutical companies have increased their interest in investigating plants as sources for new phytotherapeutic agents with proven efficacy, quality, and safety.^[3] The plants have therapeutic benefits, such as antioxidant, anti-inflammatory, antimicrobial, antiseptic, and anti-collagenase properties.^[4] The role of plants (or plant products) and their role in the management of periodontal diseases are reviewed in this study.

History

There is a long and effective history of plants usage in the field of dental health. A review by Lewis and Elvin, noted a quotation credited to the prophet Muhammed: “the Miswak (chewing stick) is an implement for the cleaning of teeth and it pleases God.” Even today countries such as Southern United States, Tropical America, Southern Asian, and African communities reported its use. A Sumerian clay slab discovered from Nagpur, India which is about 5000 year old has been found as the oldest written evidence of treatment with medicinal plants. It encompasses 12 recipes referring to over 250 various plants for drug preparation, including some alkaloids such as henbane, mandrake, and poppy. The Vedas, which is an Indian holy book, also mentions treatment with plants. Ancient Indian ayurvedic literatures such as Susruta Samhita and Charaka Samhita also have given contributions in this field. The Ebers Papyrus, dated around 1550 BC, comprised 800 prescriptions referring to 700 plant species and drugs which is used for therapy such as Aloe vera, castor oil plant, coriander, garlic, juniper, onion, and pomegranate.^[5]

Hippocrates, the “Father of Medicine,” included references of over 250 medicinal plants and herbs in his writings. The use of these medicinal plants in 19^th century turned out to be a milestone. The beginning of scientific pharmacy was marked by the discovery, validation, and isolation of alkaloids from poppy (1806), strychnos (1817), ipecacuanha (1817), quinine (1820), pomegranate (1878), and some other plants. With various newly introduced chemical methods, other active substances from medicinal plants were also identified, which includes etheric oils, saponosides, tannins, and vitamins. At present, drugs prepared from different herbal plants are available which can be used separately or in combination with other synthetic drugs. Numerous herbs used today are proved effective and safe by various evidence-based scientific literatures.^[6] For the success of any treatment with medicinal plants, accurate diagnosis of the disease as well as knowledge of the pharmacological effect of drug components are important.^[5]

Various Herbs and Their Uses in the Management of Periodontal Disease

Guava

Guava has various important constituents such as essential oils, flavonoids, phenolic compounds, tannins, triterpenoid acids, sesquiterpene alcohols, and vitamins which have excellent antioxidant, anti-inflammatory, antimicrobial, analgesic, antispasmodic, anticancer, antihyperglycemic, and hepatoprotective actions [Figure 1]. Conventionally, tender leaves of guava is used to make paste and used to maintain oral hygiene. It is antibacterial in nature against both Gram-positive and Gram-negative bacteria. Antibacterial properties are also exhibited by the bark due to the presence of tannins.^[7],[8]

Figure 1: Guava Click here to view

A study conducted in 2014 compared the double combinations of Acacia nilotica, Murraya koenigii L. Sprengel, Eucalyptus hybrid, and Psidium guajava and found that they showed efficient antimicrobial action against primary plaque colonizers.^[9] Another study conducted in 2018 for assessing the effect of guava and Vitamin C supplementation on experimental gingivitis found that the development of experimental gingivitis can be prevented by the consumption of either 200 g guava/day or 200 mg synthetic vitamin C/day.^[10]

Quercetin present in guava have excellent antibacterial actions against periodontal pathogens Aggregatibacter actinomycetemcomitans(Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn).^[11]

The anti-inflammatory action of guava has been known because of its ability to inhibit prostaglandin (PG), kinin, and histamine.^[12] It also has immunomodulatory activity on NF-kβ^[13] and also inhibited lipopolysaccharide induced NF-kβ activation.^[14] Blocking NF-kβ will prevent the inflammatory bone resorption in periodontal disease.^[15]

Neem

For 1000 of years, neem has been used in India and South Asia as a useful tool for the maintenance of healthy teeth and gums [Figure 2]. Traditional dental care practices are using neem leaves and seeds for chewing after a meal and also neem twigs for brushing. Azadirachta indica, known commonly as “neem” is a tree in the family Meliaceae which is distributed widely in Africa and Asia. Indigenous systems of medicine used almost every part of the tree for treating various human illness, especially against bacterial and fungal diseases. Neem has also been used as an astringent and antiseptic. Neem leaf extract has shown excellent antihyperglycemic and antiviral activityin vitro andin vivo on animals.^[16],[17] It also showed superior efficiency in inhibiting plaque growth for the management of periodontal diseases and for treating other oral infections.^[18] Some studies has demonstrated its broad range of antibacterial activity.^[19]

Figure 2: Neem Click here to view

Kudalkar et al., in 2014, conducted anin vitro study on the effect of A. indica (Neem) on MMP-2 and MMP-9 (matrix metalloproteinases) and found that it reduces 53.5% of MMP-2 and 52.5% of MMP-9 activity.^[20]

Vennila et al. conducted a study in chronic periodontitis patients on the effect of 10% whole neem chip used as an addition to scaling and root planing and found that the clinical parameters are statistically improved and presence of P. gingivalis strains were significantly reduced on the sites where neem chips are used.^[21]

Aloe vera

A. vera is a succulent plant species that belongs to the family Liliaceae [Figure 3]. Among 300 species of A. vera, only two species A. verahas been studied, which are Aloe barbadensis Miller and Aloe arborescens. Two different parts of A. vera leaf are a central mucilaginous part and peripheral bundle sheath cells. Parenchymal tissue present in the inner portion of the aloe leaves produces A. vera gel, which is a tasteless, jelly-like, thin, and clear material.^[22] A. vera has various pharmacological actions which include antibacterial, antioxidant,^[23] anti-inflammatory,^[24],[25] antiviral,^[26] and antifungal actions.^[27]

Figure 3: Aloe vera Click here to view

A study conducted in 2016 for the comparison of the efficiency of A. vera mouthwash and chlorhexidine on periodontal health showed that A. vera mouthwash is equally efficient as chlorhexidine in the reduction of plaque and gingivitis.^[28]

The use of A. vera in treating dental diseases is numerous. It is exceptionally useful in gingivitis and periodontitis management.^[29] It controls inflammation, gingival bleeding and also acts as a powerful antiseptic. It has antifungal properties and is used in the treatment of aphthous ulcers, denture stomatitis,^[30] cracked and split corners of the mouth. It also has various anti-inflammatory components. The carboxypeptidase present in A. vera helps in relieving pain by inactivating bradykinin by about 67%^[31] and also it has compounds which inhibits arachidonic acid oxidation and anti-PG synthesis properties, which might reduce inflammation.^[32]

A. vera showed the inhibition of the production of free oxygen radicals and depletion of the alternative and chemical pathways of complement activity.^[33] Ashouri Moghaddam et al. in 2017 conducted a study and proved the efficacy of local application of A. vera gel in chronic periodontitis patients as an addition to scaling and root planing.^[34]

Curcumin

Turmeric is a spice plant that has polyphenol curcumin in its rhizome [Figure 4]. Three types of curcuminoids are present in turmeric: curcumin (diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin. The potent anti-inflammatory actions of curcumin are attributed to several mechanisms and to its multiple molecular targets. First, it suppresses the activation of the transcription factor nuclear factor kappa-B (NF-κB), which is a key signaling molecule in the elaboration of the inflammatory response^[35],[36] as well as in cell proliferation, oncogenesis, and cell transformation.^[37] Second, curcumin downregulates the expression of cyclooxygenase-2, an enzyme that catalyzes the synthesis of PGs and is linked to most forms of inflammation, including periodontitis. It also inhibits synthesis of inducible nitric oxide synthase, a strong pro-inflammatory molecule that is regulated by NF-κB), and promotes its direct degradation.^[38] Curcumin has been reported to possess both antibacterial^[39],[40] and antifungal properties.^[41] It acts both as bacteriostatic^[42] and bactericidal for various disease-causing Gram-positive bacteria^[43] like Staphylococcus aureus, as well as Gram-negative bacteria, including Pseudomonas aeruginosa,^[44]Klebsiella pneumoniae,^[45] as well as different fungal species such as Candida albicans and Paracoccidioides brasiliensis.^[46] Various mechanisms of actions have been reported concerning the antibacterial properties of curcumin. It has been proposed that bacterial cell division can be inhibited curcumin^[47] and it can induce bacterial membrane permeabilization, leading to permanent damage and cellular death in both Gram-positive and Gram-negative bacteria.^[48] Curcumin inhibits Streptococcus mutans biofilm formation by suppressing sortase A which is an enzyme responsible for the bacterial attachment^[49] to extracellular matrix proteins and human tooth surfaces.^[50] Several reports have demonstrated that curcumin has synergistic antibacterial effects with different antibiotics such as vancomycin, cefixime, and tetracycline against P. aeruginosa and S. aureus by negatively affecting their virulence, quorum sensing, and biofilm initiation.^[51]

Figure 4: Curcumin Click here to view

Curylofo-Zotti et al., in 2018, conducted a study in an experimental periodontitis model for the comparison of natural and chemically modified curcumin on inflammation of periodontium and associated bone resorption and found that chemically modified curcumin is more capable in reducing LPS-induced model of periodontitis.^[52]

Tulsi

Tulsi (Ocimum sanctum) has a chemical composition which is highly complex and contains various compounds and nutrients which are biologically active in nature [Figure 5]. The leaves of O. sanctum have antibacterial agents which are present mainly as essential oils. Eugenol, caryophyllene, germarene-A, clemene, and caryophyllene oxide are the five major constituents of these essential oils. Ursolic acid, rosmarinic acid, and oleanolic acid are the other biologically active compounds which are present in the form of phytochemicals. These essential oils and biologically active compounds are effective against Gram-positive and Gram-negative bacteria due to their antibacterial properties.^[53],[54] They can cause cytoplasmic membrane damage of microbial strains by stimulating cellular potassium release. These mechanisms which are effective against systemic disease-causing bacteria might have also acted against the periodontal pathogen A.actinomycetemcomitans in human dental plaque.

Figure 5: Tulsi Click here to view

Very few studies in the literature search have tested the antimicrobial action of O. sanctum on oral disease-causing organisms. A clinical study by Gupta et al. found that the effectiveness of O. sanctum mouthrinse in reducing plaque and gingivitis is the same as that of chlorhexidine.^[55] Mallikarjun et al., in 2016, conducted anin vitro study and proved the antimicrobial efficacy of Tulsi leaf extract on Aa.^[56]

It has also been postulated that Tulsi has an immunomodulatory effect and acts by increasing the levels of interferon, interleukin-4, and T helper cells which will strengthen the host response to infections.^[57]

Pineapple

Pineapple (Ananas comosus) is a tropical fruit which is rich in vitamins, enzymes, and antioxidants [Figure 6]. The plant belongs to the Bromeliaceae family. Bromelain, which is an elementary extract from pineapple is the reason for the therapeutic qualities of pineapple. It contains various proteinases along with other compounds. Bothin vitro and in vivo, it exhibits various antiedematous, fibrinolytic, anti-inflammatory, and antithrombotic activities^[58] and can be considered as a substitute for Non-Steroidal Anti-inflammatory agents, glucocorticoids, and immunomodulators.^[59],[60] It is believed that bromelain decreases the potential adverse effects associated with antibiotic toxicity by increasing the absorption of antibiotics which helps in its better distribution in tissues.^[60] A study conducted in 2014 proved the efficient antibacterial property of bromelain against various aerobic and anaerobic microorganisms (S. mutans, P. gingivalis,  Escherichia ^{More Details} coli and A. actenomycemcomitans).^[61] A recent study conducted in 2017 proved the anti-plaque and anti-gingivitis efficacy of a dentifrice containing bromelain.^[62] Even though the toxic effects are less, researchers limited its use in patients with kidney and liver problems and hemophilia, due to anticoagulatory effects.^[60]

Figure 6: Pineapple Click here to view

Grape seed extract

Grape seed extract (GSE) is obtained from seeds of Vitis vinifera [Figure 7]. It is a polyphenolic compound which is naturally occurring and also has been proposed as an efficient immunomodulator agent due to its proanthocyanidin content. It possesses a wide range of biological activities such as antioxidant, anticarcinogenic, and anti-inflammatory effects.^{[63],[64],[65]} GSE demonstrates its anti-inflammatory effect by regulating the release and gene expression of pro-inflammatory and anti-inflammatory cytokines.^[66] The polyphenolic compounds which are present in grape seeds are mainly gallic acid, monomeric catechin, and epicatechin, oligomeric and polymeric procyanidins.^[67] These polyphenolic compounds showed various biological effects, such as antioxidant or antimicrobial. Rayyan et al., in 2018, conducted a study and found that GSE reduces gingival index and plaque index in chronic periodontitis patients.^[68]

Figure 7: Grape Seed Click here to view

GSE reduces the osteoclastic activity, may strongly inhibit osteoclast differentiation, and stimulate the formation of bone through its positive effect on osteoblast differentiation, and thus may be beneficial for the treatment of inflammation associated with bone destruction.^[69] It also demonstrates protection against collagen breakdown,^[70] and also significantly decrease the maturation of dental biofilm by its bacteriostatic effect on the anaerobes, and therefore, may be used in the prevention of periodontal disease.

A recent study by Toker et al. in 2018 found that GSE administration may reduce the inflammation of periodontium and alveolar bone loss by decreasing the levels of MMP-8 and HIF-1α.^[71]

Pomegranate

Punica granatum belonging to family Punicaceae is more commonly known as pomegranate [Figure 8].^[72] The word pomegranate means Apple (“Pomum”) and seeded (“granatus”). The most beneficial components of pomegranate are ellagitannins, flavonoids, punicic acid, anthocyanins, anthocyanidins, and estrogenic flavones. Pomegranate peel has been shown to have anti-inflammatory,^[73] antimutagenic,^[74]and antifungal activity. Tannin content in pomegranate juice, has anti-oxidative, antihypertensive, anti-atherosclerotic, and anti-aging properties.^[75]

Figure 8: Pomegranate Click here to view

Vasconcelos et al. in 2006, studied the antimicrobial action of pomegranate gel against S. mutans, Streptococcus mitis, and C. albicans and found that it is efficient in the inhibition of microbial adherence.^[76] Recently in 2016, Aparecida Procópio Gomes et al. also studied and proved the antimicrobial efficacy of P. granatum against P. gingivalis.^[77] It has also shown antibacterial efficacy against A.actinomycetemcomitans (Aa), P. gingivalis (Pg), P. intermedia (Pi), which are the most important periodontal pathogens.^[78] Thus, it can be used as an adjunct with mechanical debridement in the treatment of gingivitis and periodontitis.^[79]

Punicic acid which is the major ingredient of pomegranate is an excellent anti-inflammatory compound with a property to suppress PG production.^[80],[81] It can also inhibit NF-κB activity which will prevent inflammation-induced bone resorption and a promising mechanism to treat periodontitis.^[82]

Pomegranate extract is known for its wound healing properties. It is known to induce increased fibroblast migration and proliferation, formation of collagen and angiogenesis [Table 1].^[83],[84]

Table 1: Plant products, components and action Click here to view

Conclusion

The use of herbs for medicine has been successfully used in dentistry as antioxidant, antiseptic, and analgesic. These natural phytotherapeutical agents can be used as a substitute to antibiotics. They will improve the immunity and help in the healing of oral infections. Antimicrobial activities of these drugs have been found to be particularly useful for the management of periodontal diseases. However, before using it as a part of everyday practice, well-controlled clinical trials are mandatory to justify the use of these traditional therapeutic methods in the dental field and also to understand whether they offer therapeutic benefits, either alone or in combination with different conventional therapies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]