|Year : 2019 | Volume
| Issue : 2 | Page : 82-89
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|
Dr. M M Dayakar
Department of Periodontology, K V G Dental College and Hospital, Sullia, Dakshina Kannada, Karnataka
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 18];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. 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. 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. The plants have therapeutic benefits, such as antioxidant, anti-inflammatory, antimicrobial, antiseptic, and anti-collagenase properties. 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.
Hippocrates, the “Father of Medicine,” included references of over 250 medicinal plants and herbs in his writings. The use of these medicinal plants in 19th 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. 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.
| Various Herbs and Their Uses in the Management of Periodontal Disease|| |
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.,
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. 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.
Quercetin present in guava have excellent antibacterial actions against periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn).
The anti-inflammatory action of guava has been known because of its ability to inhibit prostaglandin (PG), kinin, and histamine. It also has immunomodulatory activity on NF-kβ and also inhibited lipopolysaccharide induced NF-kβ activation. Blocking NF-kβ will prevent the inflammatory bone resorption in periodontal disease.
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., It also showed superior efficiency in inhibiting plaque growth for the management of periodontal diseases and for treating other oral infections. Some studies has demonstrated its broad range of antibacterial activity.
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.
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.
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. vera has 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. A. vera has various pharmacological actions which include antibacterial, antioxidant, anti-inflammatory,, antiviral, and antifungal actions.
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.
The use of A. vera in treating dental diseases is numerous. It is exceptionally useful in gingivitis and periodontitis management. 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, 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% and also it has compounds which inhibits arachidonic acid oxidation and anti-PG synthesis properties, which might reduce inflammation.
A. vera showed the inhibition of the production of free oxygen radicals and depletion of the alternative and chemical pathways of complement activity. 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.
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, as well as in cell proliferation, oncogenesis, and cell transformation. 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. Curcumin has been reported to possess both antibacterial, and antifungal properties. It acts both as bacteriostatic and bactericidal for various disease-causing Gram-positive bacteria like Staphylococcus aureus, as well as Gram-negative bacteria, including Pseudomonas aeruginosa,Klebsiella pneumoniae, as well as different fungal species such as Candida albicans and Paracoccidioides brasiliensis. 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 and it can induce bacterial membrane permeabilization, leading to permanent damage and cellular death in both Gram-positive and Gram-negative bacteria. Curcumin inhibits Streptococcus mutans biofilm formation by suppressing sortase A which is an enzyme responsible for the bacterial attachment to extracellular matrix proteins and human tooth surfaces. 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.
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.
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., 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.
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. Mallikarjun et al., in 2016, conducted anin vitro study and proved the antimicrobial efficacy of Tulsi leaf extract on Aa.
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.
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 and can be considered as a substitute for Non-Steroidal Anti-inflammatory agents, glucocorticoids, and immunomodulators., 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. 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). A recent study conducted in 2017 proved the anti-plaque and anti-gingivitis efficacy of a dentifrice containing bromelain. Even though the toxic effects are less, researchers limited its use in patients with kidney and liver problems and hemophilia, due to anticoagulatory effects.
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.,, GSE demonstrates its anti-inflammatory effect by regulating the release and gene expression of pro-inflammatory and anti-inflammatory cytokines. The polyphenolic compounds which are present in grape seeds are mainly gallic acid, monomeric catechin, and epicatechin, oligomeric and polymeric procyanidins. 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.
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. It also demonstrates protection against collagen breakdown, 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.
Punica granatum belonging to family Punicaceae is more commonly known as pomegranate [Figure 8]. 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, antimutagenic, and antifungal activity. Tannin content in pomegranate juice, has anti-oxidative, antihypertensive, anti-atherosclerotic, and anti-aging properties.
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. Recently in 2016, Aparecida Procópio Gomes et al. also studied and proved the antimicrobial efficacy of P. granatum against P. gingivalis. It has also shown antibacterial efficacy against A. actinomycetemcomitans (Aa), P. gingivalis (Pg), P. intermedia (Pi), which are the most important periodontal pathogens. Thus, it can be used as an adjunct with mechanical debridement in the treatment of gingivitis and periodontitis.
Punicic acid which is the major ingredient of pomegranate is an excellent anti-inflammatory compound with a property to suppress PG production., It can also inhibit NF-κB activity which will prevent inflammation-induced bone resorption and a promising mechanism to treat periodontitis.
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].,
| 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.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Palombo EA. Traditional medicinal plant extracts and natural products with activity against oral bacteria: Potential application in the prevention and treatment of oral diseases. Evid Based Complement Alternat Med 2011;2011:680354.
Botelho MA, Bezerra Filho JG, Correa LL, Fonseca SG, Montenegro D, Gapski R, et al.
Effect of a novel essential oil mouthrinse without alcohol on gingivitis: A double-blinded randomized controlled trial. J Appl Oral Sci 2007;15:175-80.
Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res 2000;33:179-89.
Moro MG, Silveira Souto ML, Franco GCN, Holzhausen M, Pannuti CM. Efficacy of local phytotherapy in the nonsurgical treatment of periodontal disease: A systematic review. J Periodontal Res 2018;53:288-97.
Petrovska BB. Historical review of medicinal plants' usage. Pharmacogn Rev 2012;6:1-5.
Cohan RP, Jacobsen PL. Herbal supplements: Considerations in dental practice. J Calif Dent Assoc 2000;28:600-10.
Geoghegan F, Wong RW, Rabie AB. Inhibitory effect of quercetin on periodontal pathogens in vitro
. Phytother Res 2010;24:817-20.
Ravi K, Divyashree P. Psidium guajava
: A review on its potential as an adjunct in treating periodontal disease. Pharmacogn Rev 2014;8:96-100.
Chandra Shekar BR, Nagarajappa R, Singh R, Thaku R. Antimicrobial efficacy of the combinations of Acacia nilotica
, Murraya koenigii
L. Sprengel, eucalyptus hybrid and Psidium guajava
on primary plaque colonizers. J Basic Clin Pharm 2014;5:115-9.
Amaliya A, Risdiana AS, Van der Velden U. Effect of guava and vitamin C supplementation on experimental gingivitis: A randomized clinical trial. J Clin Periodontol 2018;45:959-67.
Prabu GR, Gnanamani A, Sadulla S. Guaijaverin – A plant flavonoid as potential antiplaque agent against Streptococcus mutans
. J Appl Microbiol 2006;101:487-95.
Kavimani S, Ilango R, Vertichelvan T. Anti – Inflammatory activity of volatile oil of psidium guajava
. Anc Sci Life 1998;17:300-4.
Kaileh M, Vanden Berghe W, Boone E, Essawi T, Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J Ethnopharmacol 2007;113:510-6.
Choi SY, Hwang JH, Park SY, Jin YJ, Ko HC, Moon SW, et al.
Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage cells by inhibition of transcription factor NF-kappaB. Phytother Res 2008;22:1030-4.
Koide M, Kinugawa S, Takahashi N, Udagawa N. Osteoclastic bone resorption induced by innate immune responses. Periodontol 2000 2010;54:235-46.
Chattopadhyay RR. Possible mechanism of antihyperglycemic effect of Azadirachta indica
leaf extract: Part V. J Ethnopharmacol 1999;67:373-6.
Parida MM, Upadhyay C, Pandya G, Jana AM. Inhibitory potential of neem (Azadirachta indica
Juss) leaves on Dengue virus type-2 replication. J Ethnopharmacol 2002;79:273-8.
Patel VK, Venkatakrishna-Bhatt H. Folklore therapeutic indigenous plants in periodontal disorders in India (review, experimental and clinical approach). Int J Clin Pharmacol Ther Toxicol 1988;26:176-84.
Rao DV, Singh I, Chopra P, Chhabra PC, Ramanujalu G.In vitro
antibacterial activity of neem oil. Indian J Med Res 1986;84:314-6.
Kudalkar MD, Nayak A, Bhat KS, Nayak RN. Effect of Azadirachta indica
(Neem) and Aloe vera
as compared to subantimicrobial dose doxycycline on matrix metalloproteinases (MMP)-2 and MMP-9: Anin vitro
study. Ayu 2014;35:85-9.
] [Full text]
Vennila K, Elanchezhiyan S, Ilavarasu S. Efficacy of 10% whole Azadirachta indica
(Neem) chip as an adjunct to scaling and root planning in chronic periodontitis: A clinical and microbiological study. Indian J Dent Res 2016;27:15-21.
] [Full text]
Wynn RL. Aloe vera
Gel: Update for dentistry. Gen Dent 2005;53:6-9.
Yagi A, Kabash A, Okamura N, Haraguchi H, Moustafa SM, Khalifa TI, et al.
Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera
. Planta Med 2002;68:957-60.
Shelton RM. Aloe vera
. Its chemical and therapeutic properties. Int J Dermatol 1991;30:679-83.
Vázquez B, Avila G, Segura D, Escalante B. Antiinflammatory activity of extracts from Aloe vera
Gel. J Ethnopharmacol 1996;55:69-75.
Sydiskis RJ, Owen DG, Lohr JL, Rosler KH, Blomster RN. Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 1991;35:2463-6.
Rosca-Casian O, Parvu M, Vlase L, Tamas M. Antifungal activity of Aloe vera
leaves. Fitoterapia 2007;78:219-22.
Vangipuram S, Jha A, Bhashyam M. Comparative efficacy of Aloe vera
mouthwash and chlorhexidine on periodontal health: A randomized controlled trial. J Clin Exp Dent 2016;8:e442-7.
Grindlay D, Reynolds T. The Aloe vera
phenomenon: A review of the properties and modern uses of the leaf parenchyma gel. J Ethnopharmacol 1986;16:117-51.
Tello CG, Ford P, Iacopino AM.In vitro
evaluation of complex carbohydrate denture adhesive formulations. Quintessence Int 1998;29:585-93.
Fujita K, Teradaira R, Nagatsu T. Bradykinase activity of aloe extract. Biochem Pharmacol 1976;25:205.
Bautista-Pérez R, Segura-Cobos D, Vázquez-Cruz B.In vitro
antibradykinin activity of Aloe barbadensis
Gel. J Ethnopharmacol 2004;93:89-92.
Hart LA, van Enckevort PH, van Dijk H, Zaat R, de Silva KT, Labadie RP. Two functionally and chemically distinct immunomodulatory compounds in the gel of Aloe vera
. J Ethnopharmacol 1988;23:61-71.
Ashouri Moghaddam A, Radafshar G, Jahandideh Y, Kakaei N. Clinical evaluation of effects of local application of Aloe vera
gel as an adjunct to scaling and root planning in patients with chronic periodontitis. J Dent (Shiraz) 2017;18:165-72.
Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 1995;270:24995-5000.
Giuliani C, Napolitano G, Bucci I, Montani V, Monaco F. Nf-kB transcription factor: Role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin Ter 2001;152:249-53.
Luque I, Gélinas C. Rel/NF-kappa B and I kappa B factors in oncogenesis. Semin Cancer Biol 1997;8:103-11.
Ben P, Liu J, Lu C, Xu Y, Xin Y, Fu J, et al.
Curcumin promotes degradation of inducible nitric oxide synthase and suppresses its enzyme activity in RAW 264.7 cells. Int Immunopharmacol 2011;11:179-86.
Schraufstatter E, Bernt H. Antibacterial action of curcumin and related compounds. Nature 1949;164:456.
Bhavani Shankar TN, Sreenivasa Murthy V. Effect of turmeric (Curcuma longa
) fractions on the growth of some intestinal and pathogenic bacteria in vitro
. Indian J Exp Biol 1979;17:1363-6.
Apisariyakul A, Vanittanakom N, Buddhasukh D. Antifungal activity of turmeric oil extracted from Curcuma longa
). J Ethnopharmacol 1995;49:163-9.
Shahi SK, Shukla AC, Bajaj AK, Banerjee U, Rimek D, Midgely G, et al.
Broad spectrum herbal therapy against superficial fungal infections. Skin Pharmacol Appl Skin Physiol 2000;13:60-4.
Negi PS, Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Antibacterial activity of turmeric oil: A byproduct from curcumin manufacture. J Agric Food Chem 1999;47:4297-300.
Packiavathy IA, Priya S, Pandian SK, Ravi AV. Inhibition of biofilm development of uropathogens by curcumin – An anti-quorum sensing agent from Curcuma longa
. Food Chem 2014;148:453-60.
Magesh H, Kumar A, Alam A, Priyam, Sekar U, Sumantran VN, et al.
Identification of natural compounds which inhibit biofilm formation in clinical isolates of Klebsiella pneumoniae
. Indian J Exp Biol 2013;51:764-72.
Martins CV, da Silva DL, Neres AT, Magalhães TF, Watanabe GA, Modolo LV, et al.
Curcumin as a promising antifungal of clinical interest. J Antimicrob Chemother 2009;63:337-9.
Rai D, Singh JK, Roy N, Panda D. Curcumin inhibits FtsZ assembly: An attractive mechanism for its antibacterial activity. Biochem J 2008;410:147-55.
Tyagi P, Singh M, Kumari H, Kumari A, Mukhopadhyay K. Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS One 2015;10:e0121313.
Hu P, Huang P, Chen MW. Curcumin reduces Streptococcus mutans
biofilm formation by inhibiting sortase A activity. Arch Oral Biol 2013;58:1343-8.
Song J, Choi B, Jin EJ, Yoon Y, Choi KH. Curcumin suppresses Streptococcus mutans
adherence to human tooth surfaces and extracellular matrix proteins. Eur J Clin Microbiol Infect Dis 2012;31:1347-52.
Rudrappa T, Bais HP. Curcumin, a known phenolic from Curcuma longa
, attenuates the virulence of Pseudomonas aeruginosa
PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 2008;56:1955-62.
Curylofo-Zotti FA, Elburki MS, Oliveira PA, Cerri PS, Santos LA, Lee HM, et al.
Differential effects of natural curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis. Arch Oral Biol 2018;91:42-50.
Prakash P, Gupta N. Therapeutic uses of Ocimum sanctum
Linn (Tulsi) with a note on eugenol and its pharmacological actions: A short review. Indian J Physiol Pharmacol 2005;49:125-31.
Mondal S, Mirdha BR, Mahapatra SC. The science behind sacredness of Tulsi (Ocimum sanctum
Linn.). Indian J Physiol Pharmacol 2009;53:291-306.
Gupta D, Bhaskar DJ, Gupta RK, Karim B, Jain A, Singh R, et al.
Arandomized controlled clinical trial of Ocimum sanctum
and chlorhexidine mouthwash on dental plaque and gingival inflammation. J Ayurveda Integr Med 2014;5:109-16.
] [Full text]
Mallikarjun S, Rao A, Rajesh G, Shenoy R, Pai M. Antimicrobial efficacy of Tulsi leaf (Ocimum sanctum
) extract on periodontal pathogens: Anin vitro
study. J Indian Soc Periodontol 2016;20:145-50.
] [Full text]
Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR, Padhi MM, et al.
Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum
Linn.) leaf extract on healthy volunteers. J Ethnopharmacol 2011;136:452-6.
Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: A review. Biotechnol Res Int 2012;2012:976203.
Engwerda CR, Andrew D, Ladhams A, Mynott TL. Bromelain modulates T cell and B cell immune responsesin vitro
and in vivo
. Cell Immunol 2001;210:66-75.
Maurer HR. Bromelain: Biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001;58:1234-45.
Praveen NC, Rajesh A, Madan M, Chaurasia VR, Hiremath NV, Sharma AM.In vitro
evaluation of antibacterial efficacy of pineapple extract (Bromelain) on periodontal pathogens. J Int Oral Health 2014;6:96-8.
Tadikonda A, Pentapati KC, Urala AS, Acharya S. Anti-plaque and anti-gingivitis effect of papain, bromelain, miswak and neem containing dentifrice: A randomized controlled trial. J Clin Exp Dent 2017;9:e649-53.
Li WG, Zhang XY, Wu YJ, Tian X. Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds. Acta Pharmacol Sin 2001;22:1117-20.
Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, leucoselect. J Clin Pharm Ther 1998;23:385-9.
Zhang XY, Bai DC, Wu YJ, Li WG, Liu NF. Proanthocyanidin from grape seeds enhances anti-tumor effect of doxorubicin bothin vitro
and in vivo
. Pharmazie 2005;60:533-8.
Ahmad SF, Zoheir KM, Abdel-Hamied HE, Attia SM, Bakheet SA, Ashour AE, et al.
Grape seed proanthocyanidin extract protects against carrageenan-induced lung inflammation in mice through reduction of pro-inflammatory markers and chemokine expressions. Inflammation 2014;37:500-11.
Monagas M, Gómez-Cordovés C, Bartolomé B, Laureano O, Ricardo da Silva JM. Monomeric, oligomeric, and polymeric flavan-3-ol composition of wines and grapes from Vitis vinifera
L. Cv. Graciano
, and cabernet sauvignon. J Agric Food Chem 2003;51:6475-81.
Rayyan M, Terkawi T, Abdo H, Abdel Azim D, Khalaf A, AlKhouli Z. Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A randomized clinical study. J Investig Clin Dent 2018;9:e12318.
Park JS, Park MK, Oh HJ, Woo YJ, Lim MA, Lee JH, et al.
Grape-seed proanthocyanidin extract as suppressors of bone destruction in inflammatory autoimmune arthritis. PLoS One 2012;7:e51377.
La VD, Bergeron C, Gafner S, Grenier D. Grape seed extract suppresses lipopolysaccharide-induced matrix metalloproteinase (MMP) secretion by macrophages and inhibits human MMP-1 and -9 activities. J Periodontol 2009;80:1875-82.
Toker H, Balci Yuce H, Lektemur Alpan A, Gevrek F, Elmastas M. Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis. J Periodontal Res 2018;53:478-86.
Salgado AD, Maia JL, Pereira SL, de Lemos TL, Mota OM. Antiplaque and antigingivitis effects of a gel containing Punica granatum
Linn extract: A double-blind clinical study in humans. J Appl Oral Sci 2006;14:162-6.
Bachoual R, Talmoudi W, Boussetta T, Braut F, El-Benna J. An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidasein vitro
and attenuates lung inflammation in mice. Food Chem Toxicol 2011;49:1224-8.
Zahin M, Aqil F, Ahmad I. Broad spectrum antimutagenic activity of antioxidant active fraction of Punica granatum
L. Peel extracts. Mutat Res 2010;703:99-107.
Stowe CB. The effects of pomegranate juice consumption on blood pressure and cardiovascular health. Complement Ther Clin Pract 2011;17:113-5.
Vasconcelos LC, Sampaio FC, Sampaio MC, Pereira Mdo S, Higino JS, Peixoto MH, et al.
Minimum inhibitory concentration of adherence of Punica granatum
Linn (pomegranate) gel against S. mutans
, S. mitis
and C. albicans
. Braz Dent J 2006;17:223-7.
Aparecida Procópio Gomes L, Alves Figueiredo LM, Luiza do Rosário Palma A, Corrêa Geraldo BM, Isler Castro KC, Ruano de Oliveira Fugisaki L. Punica granatum
L. (Pomegranate) extract:In vivo
study of antimicrobial activity against Porphyromonas gingivalis
in Galleria mellonella
model. ScientificWorldJournal 2016;2016:8626987.
Bhadbhade SJ, Acharya AB, Rodrigues SV, Thakur SL. The antiplaque efficacy of pomegranate mouthrinse. Quintessence Int 2011;42:29-36.
Somu CA, Ravindra S, Ajith S, Ahamed MG. Efficacy of a herbal extract gel in the treatment of gingivitis: A clinical study. J Ayurveda Integr Med 2012;3:85-90. [Full text]
Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM. Bioavailable constituents/metabolites of pomegranate (Punica granatum
L) preferentially inhibit COX2 activity ex vivo
and IL-1beta-induced PGE2 production in human chondrocytes in vitro
. J Inflamm (Lond) 2008;5:9.
Abdollahzadeh Sh, Mashouf R, Mortazavi H, Moghaddam M, Roozbahani N, Vahedi M. Antibacterial and antifungal activities of Punica granatum
peel extracts against oral pathogens. J Dent (Tehran) 2011;8:1-6.
Ishikawa I. Host responses in periodontal diseases: A preview. Periodontol 2000 2007;43:9-13.
Singer AJ, Clark RA. Cutaneous wound healing. N
Engl J Med 1999;341:738-46.
Yan H, Peng KJ, Wang QL, Gu ZY, Lu YQ, Zhao J, et al.
Effect of pomegranate peel polyphenol gel on cutaneous wound healing in alloxan-induced diabetic rats. Chin Med J (Engl) 2013;126:1700-6.
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