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REVIEW ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 106-109

Glycyrrhiza glabra: Its role in dentistry


1 Department of Pediatric and Preventive Dentistry, Government Dental College and Hospital, Aurangabad, Maharashtra, India
2 Department of Mechanical Engineering, Government College of Engineering, Aurangabad, Maharashtra, India

Date of Submission24-Dec-2019
Date of Acceptance19-Mar-2020
Date of Web Publication08-Jul-2020

Correspondence Address:
Dr. Chaitali Hambire
17, Shreekunj, Samadhan Colony, Behind Sessions Court, Aurangabad - 431 005, Maharashtra
India
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DOI: 10.4103/srmjrds.srmjrds_94_19

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  Abstract 

Glycyrrhiza glabra has been used as medicine in Ayurveda and flavouring herb for more than 4000 years. It is reported to have antiviral, anticancer, anti-ulcer, anti-diabetic, anti-oxidant,anti-malarial, anti-fungal, anti-bacterial, immune-stimulant, antithrombotic, anticonvulsant, anti-allergenic and expectorant activities. The presence of alkaloids, tannins, essential oils and flavonoids prevent the adherence of bacteria to the tooth surfaces, inhibit glucan production and have inhibitory effect on amylases. This paper presents a review of role of Glycyrrhiza glabra in dentistry.

Keywords: Dental, glycyrrhiza glabra, oral cancers, recurrent aphthous ulcers


How to cite this article:
Hambire C, Hambire U. Glycyrrhiza glabra: Its role in dentistry. SRM J Res Dent Sci 2020;11:106-9

How to cite this URL:
Hambire C, Hambire U. Glycyrrhiza glabra: Its role in dentistry. SRM J Res Dent Sci [serial online] 2020 [cited 2020 Aug 10];11:106-9. Available from: http://www.srmjrds.in/text.asp?2020/11/2/106/289176


  Introduction Top


Ayurveda is one of the traditional forms of medicinal systems of India. It uses >7000 varieties of medicinal plant extract for the management of different diseases. With the emergence of many multi-drug resistant pathogens and the rising cost of drugs, there is an increasing trend toward the development of drugs from natural sources. Glycyrrhiza glabra has been used as medicine in Ayurveda and flavoring herb for > 4000 years.[1] The term Glycyrrhiza comes from the ancient Greek words; glycos meaning sweet and rhiza meaning root. G. glabra Linn is commonly known as Yashti-madhuh. Madhuka (Sanskrit) Jashtimadhu, Jaishbomodhu (Bengali) Jethimadhu (Gujarat) Jothi-madh, Mulhatti (Hindi) Yastimadhuka, atimaddhura (Kannada) Iratimadhuram (Malayalam) Jeshtamadha (Marathi) Jatimadhu (Oriya) Atimaduram (Tamil) Atimadhuranu, Yashtimadhukam (Telugu) Licorice, Liquorice, Sweetwood (English).[2]


  Description of Plant Top


G. glabra is a perennial shrub growing to the height of 1–2.5 m. It has compound, imparipinnate, alternate leaves. Each leaf has 4–7 pairs of oblong, elliptical or lanceolate leaflets. The flowers are papilionaceous lavender to violet in color. Its fruit is a compressed legume or pod, up to 1.5 cm long, erect, glabrous, with reticulous pitting containing 3–5 brown, reniform seeds. Its root system is composed of 1.5 cm long taproot with horizontal stolons. These stolons are the source of commercial liquorice. Glycyrrhizin consists of 10%–25% of liquorice, which imparts sweetness. It is fifty times sweeter than refined sugar.[3]


  Chemical Constituents of Glycyrrhiza Glabra Top


The roots are rich in lavonoid rich fractions include liquirtin, isoliquertin liquiritigenin and rhamnoliquirilin and five new flavonoids-glucoliquiritin apioside, prenyllicoflavone A, shinflavanone, shinpterocarpin and 1-metho-xyphaseolin. It also contains licopyranocoumarin, licoarylcoumarin, glisoflavone and new coumarin-GU-12 also isolated. Four new isoprenoid-substituted phenolic constituents– semilicoisoflavone B, 1-methoxyficifolinol, isoangustone A, and licoriphenone. Glycyrrhizin (glycyrrhizic acid; glycyrrhizinate) is a saponin compound comprised of a triterpenoid aglycone, glycyrrhetic acid (glycyrrhetinic acid; enoxolone) conjugated to a disaccharide of glucuronic acid. Both glycyrrhizin and glycyrrhetic acid can exist in the 18α and 18 β stereoisomers. As a tribasic acid, glycyrrhizin can form a variety of salts and occurs naturally in licorice root as the calcium and potassium salts.[3]


  Medicinal Uses Top


It is reported to have antiviral, anticancer, anti-ulcer, anti-diabetic, anti-oxidant, anti-thrombic, anti-malarial, anti-fungal, anti-bacterial, immune-stimulant, antithrombotic, anticonvulsant, anti-allergenic and expectorant activities. The roots are proved to have beneficial role as antidepressant, hypotensive hepatoprotective, spasmolytic, memory strengthening activity, demulcent property.[4] It has proved to be effective in management of gout, asthma, sore throat, tonsillitis, flatulence, sexual debility, epilepsy, hyperdypsia, fever, coughs, skin diseases, swellings, acidity, leucorrhoea, bleeding, jaundice, hiccough, hoarseness, and vitiated conditions of vata dosha, gastralgia, cephalalgia, ophthalmopathy and pharyngodnia. Different medicinal oils containing G. glabra have been effectively used in treatment of epilepsy, paralysis, rheumatism, haemorrhagic diseases, diarrhoea, fevers, fever with delirium and anuria.[5]


  Commercial Uses Top


Due to its inherent sweetness it has been used as food in the confectionery industry such as sweets, alcohol free drinks etc., and in the tobacco industry. The dried licorice is eat as confectionery. It's been used as flavouring agent in laxatives, beer, soft drinks and pharmaceutical products. It is also used as a foaming agent in beers and fire extinguishers.[6]


  Role in Dentistry Top


Dental caries

Glycrrhizin, Glycyrrhizol-A, 1 methoxyficifolinol, licorisoflavin A in G. glabra have proved to be effective in prevention of dental caries. The presence of alkaloids, tannins, essential oils and flavonoids prevent the adherence of bacteria to the tooth surfaces, inhibit glucan production and have inhibitory effect on amylases. Glabridine, one of the important constituent, is active against both gram-positive strains and gram-negative strains. In addition, the presence of glycyrrhizin, glycyrrhetinic acid, flavonoids, asparagine, isoflavonoids and chalcones improves its antiadhesive and antimicrobial properties. The flavonoids namely 1 methoxyficifolinol, licorisoflavan A and 6,8-diprenylgenistein isolated from Glycyrrhiza uralensis have shown to completely inhibit the formation of biofilm hence recommended gargling solutions and in dentrifices for prevention of dental caries.[7],[8],[9],[10]

Pterocarpenes namely glycyrrhizol A and glycyrrhizol B along with four known isoflavonoids, 5-O-methylglycryol, isoglycyrol, 6,8-diisoprenyl-5, 7, 4´-trihydroxyisoflavone and gancaonin G extracted from the roots of G. uralensis have shown activity against Streptococcus mutans where as glycyrrhizol A and 6,8-diisopreny l-5, 7, 4'-trihydroxyisoflavone had highest antimicrobial activity against these bacteria. Depending on these findings a sugar-free orange flavoured liquorice lollipop containing glycyrrhizol A for caries prevention was prepared by Hu et al.[11] Their results show that the liquorice lollipops are safe and effective against S. mutans when consumed for 10 days (twice daily) and lead to a marked reduction in salivary S. mutans.[11] Liu et al. conducted anin vitro study and reported that glycyrrhizic acid inhibits the multiplication and acid production of S. mutans thereby inhibiting the growth of these bacteria in vitro.[12] A study conducted on pediatric patients (N = 60), aged 7–14 years, showed that aqueous and ethanolic liquorice extracts used as mouth wash led to an immediate rise in salivary pH. The results showed an immediate antimicrobial action of liquorice extracts, with limited retentivity. Licorice was found to be potent cariostatic agents palatable by children.[13]

Gingival and periodontal diseases

An extract of G. uralensis along its major isoflavans, Licoricidin and Licorisoflavan A have shown to have an inhibitory effect on growth, volatile sulfur compounds production and protease activity of Porphyromonas gingivalis. These results have proved to be effective in management of fetor oris. Licochalcone A inhibits P. gingivalis biofilm formation and the host immune response, the two principal etiological factors responsible for periodontitis. 18 alpha-glycyrrhetinic acid significantly reduces P. gingivalis lipopolysaccharide-induced vascular permeability by repressing nuclear factor kappa B-dependent endothelial interleukin 8 production, suggesting its therapeutic potential in P. gingivalis-related vascular diseases. Recently anin vivo study demonstrated that liquorice extract can prevent the production of matrix metalloproteinases (MMP) by host cell and can be as effective as doxycycline in patients with chronic periodontitis.[6]

Pyrano-isoflavans from G. uralensis has shown to have antibacterial activity against S. mutans and P. gingivalis.[8] Licorice has reduced the MMP-8 levels on gingival crevicular fluid in patients with chronic periodontitis.[9]

Oral candidiasis

Candida albicans is a part of normal flora of the oral cavity and the gastrointestinal tract. It does not causes infections in healthy individuals. In case of conditions like diabetes mellitus and hypothyroidism, nutritional deficiencies like iron and B12 deficiencies, xerostomia, immunosuppressive diseases, patients suffer from Pseudomembranous candidiasis also called as thrush. Virulence factors of C. albicans such as adhesion, proteinases secretion, yeast–hyphal transition and phenotypic switching are responsible for host damage. Licochalcone A, glabridin and liquiritigenin have shown to be effective in preventing growth, biofilm formation and yeast–hyphal transition of C. albicans.[5]

Murine-acquired immunodeficiency syndrome mice (mice infected with LP-BM5 murine leukemia virus) were 100 times more susceptible to infection with C. albicans. After administration of glycyrrhizin their resistance improved compared to normal mice. Similar results were obtainedin vitro study by Kim JK et al.[6]

Recurrent aphthous ulcers: Recurrent aphthous ulcers have reported to be caused due to various etiological factors such as bacterial infection by Streptococcus sanguis, genetic history, autoimmune response, iron and folic acid deficiency. Its precipitating factor includes trauma, psychological problems, endocrine conditions and systemic diseases. Aqueous, acetone, ethanolic extracts of leaves containig Glabridin, glabrene, glycyrrhizinic acid have proved to be effective antiulcer drug.[5]

Oral cancer

Oral squamous cell carcinoma is the most common maliganat neoplasm of oral cavity. Isoliquiritigenin (ISL), a flavonoid isolated from liquorice is a novel inhibitor of tumor angiogenesis and possesses great therapeutic potential for Adenoid cystic carcinoma and can be a potential cancer chemotherapeutic agent. Studies have shown that Licochalcone A induces apoptotic cell death of oral squamous cell carcinoma cells via down regulation of Sp1 expression and can be used for the treatment of human oral squamous cell carcinoma. A group of investigators have reported that water-soluble polysaccharide (GIP1) from the roots of Glycyrrhiza inflata decreased cell viability of human oral cancer via the induction of apoptosis. ISL has anticancer effect on human oral squamous cell carcinoma. Yashtimadhu Ghrita (processed ghee) can be used to reduce chemotherapy induced mucositis in patients with cancers.[6]

Endodontic treatment

Various studies have been conducted to explore its role root canal irrigant and medicament. The extract isolated from liquorice have shown to have a significant inhibitory effect against Enterococcus faecalis.[5]


  Role of Glycyrrhiza Glabra In Radiotherapy Induced Mucositis Top


Cancers of the oral cavity account for about 10% of all malignancies in males and 4% in females.[10] Mucosal inflammation or oral mucositis is the main complication of radiotherapy of the head and neck region, which is painful and starts in early phases of treatment. It becomes more severe by continuation of treatment. This condition may become so severe to discourage patients from continuing treatment.[11],[12] Factors affecting the duration and degree of mucositis in these patients include the radiation source, cumulative dose, its intensity, volume of irradiated mucosa, smoking and alcohol consumption as well as predisposing factors such as xerostomia or infection.[12] The most widely used measurements for oral mucositis are the World Health Organization and Radiation Therapy Oncology Group scales. Also, the Oral Mucositis Assessment Scale, and a Visual Analog Pain Scale (patient reporting scale of 0–10) are used for grading of mucositis. Mucosal changes like redness, ulceration with functional outcomes such as inability to eat and pain have been assessed in these scales. Based on clinical examination, 4 distinct grades can be determined for mucositis from 0 to 4 scores. Higher grades of mucositis (Grade 3–4) are associated with loss of taste, hemorrhage, decreased intake of food and fluids, ulceration, pain, loss of voice, and low quality of life.[13] The mechanism of action of Glycyrrhiza extract on mucositis may be mediated by its anti-inflammatory effects through inhibition of activated macrophages leading to inhibition of the prostaglandin E2 production, and formation of superoxide and hydroperoxide in macrophages.[14],[15],[16] On the other hand, anti-inflammatory effects of glycyrrhizin are probably mediated by its ability to decrease generation of reactive oxygen species by neutrophils, and direct scavenging of free radicals.

In a double-blind clinical trial, 37 patients under radiotherapy in the Oncology Ward of Khoramabad Ashayer Shohada Hospital and cancer institute of Imam Khomeini Hospital were divided into intervention (n = 19) group receiving Glycyrrhiza aqueous extract and control (n = 18) group receiving placebo. Patients in the test group used Glycyrrhiza aqueous extract topically twice a day from the 1st day of starting radiotherapy until the end of the 2nd week. The oral mucosal irritation and oral mucosal wound size was 5.26 and 6.33 in the intervention group and 4.34 and 5.22 in the placebo group, respectively. Significant differences were found in the maximum grade of mucositis and oral mucosal irritation between the intervention and control groups (P < 0.001).[17]

In another double-blind, randomized prospective trial was conducted in 60 patients to compare two types of mucoadhesive films in the management of oral mucositis that occurred during head and neck cancer radiotherapy. The result showed that licorice mucoadhesive films were effective in the management of oral mucositis during radiotherapy.[18] Lyophilized licorice extract (5%w/v) was used as a mouth wash before and immediately after each session of radiation therapy have also shown clinically significant reduction in mucositis.[19]

Recommendations for future research

  1. Dentrifices and Mouth Wash: Antimicrobial flavonoids namely 1 methoxyficifolinol, licorisoflavan A and 6,8-diprenylgenistein isolated from G. uralensis have shown to completely inhibit the formation of biofilm and recommended the use of these flavonoids in oral hygiene products for gargling solutions and in dentrifices[20],[21],[22]
  2. Chewing gum: G. glabra can be incorporated in chewing gums because of its sweetness and anticariogenic properties
  3. Gel for denture stomatitis: It is effective against C. albicans. Hence can be used in management of diffuse erythema and edema of the palatal mucosa caused as result of contact with denture
  4. Sweet confectionaries: Depending on studies conducted by Hu et al. and Liu et al. lollypops and confectionaries prepared from licorice can be used by children to have beneficial effect in reducing cariogenic microbial flora[21],[22]
  5. Xerostomia: Licorice have shown to increase salivation and increase the pH of saliva, hence can be given in patients suffering from xerostomia
  6. Root canal medicament: Due to its antimicrobial and anti-inflammatory property G. glabra can be incorporated in root cal medicaments.



  Conclusion Top


Due to the increasing cost and side effects of the allopathic drugs, the demand for drugs obtained from natural sources has increased throughout the world. Medicinal plants have been used by Ayurveda since a long time. This forms a good basis for the selection and use of medicinal plants for development of novel medicines in future. G. glabra has proved to be of pharmacological and therapeutic value. The present review provides a direction for future investigators to carry out research on the various phtyochemicals of G. glabra so that its constituents can be added in dental products making it beneficial to oral care. Thein vivo studies should be directed to explore, evaluate and test the therapeutic benefits of G. glabra in dentistry.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ajagannanavar SL, Battur H, Shamarao S, Sivakumar V, Patil PU, Shanavas P. Effect of aqueous and alcoholic licorice (Glycyrrhiza glabra) root extract against Streptococcus mutans and Lactobacillus acidophilus in comparison to chlorhexidine: Anin vitro study. J Int Oral Health 2014;6:29-34.  Back to cited text no. 1
    
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Jain E, Pandey RK, Khanna R. Liquorice root extracts as potent cariostatic agents in pediatric practice. J Indian Soc Pedod Prev Dent 2013;31:146-52.  Back to cited text no. 3
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Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK. Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biochem Biophys Res Commun 2006;345:1215-23.  Back to cited text no. 6
    
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Sidhu P, et al. Therapeutic benefits of liquorice in dentistry, J Ayurveda Integr Med 2018;11:1-7. Available from: https://doi.org/10.1016/j.jaim. 2017.12.004. [Last accessed on 12 Oct 2019].  Back to cited text no. 7
    
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Bressan V, Stevanin S, Bianchi M, Aleo G, Bagnasco A, Sasso L. The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: A systematic review. Cancer Treat Rev 2016;45:105-19.  Back to cited text no. 10
    
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Franceschi S, Talamini R, Barra S, Barón AE, Negri E, Bidoli E, et al. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res 1990;50:6502-7.  Back to cited text no. 11
    
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Ferretti GA, Ash RC, Brown AT, Parr MD, Romond EH, Lillich TT. Control of oral mucositis and candidiasis in marrow transplantation: A prospective, double-blind trial of chlorhexidine digluconate oral rinse. Bone Marrow Transplant 1988;3:483-93.  Back to cited text no. 13
    
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Kubota K, Kobayashi W, Sakaki H, Nakagawa H, Kon T, Mimura M, et al. Professional oral health care reduces oral mucositis pain in patients treated by superselective intra-arterial chemotherapy concurrent with radiotherapy for oral cancer. Support Care Cancer 2015;23:3323-9.  Back to cited text no. 14
    
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Najafi S, Koujan SE, Manifar S, Kharazifard MJ, Kidi S, Hajheidary S. Preventive effect of Glycyrrhiza Glabra extract on oral mucositis in patients under head and neck radiotherapy: A randomized clinical trial. J Dent (Tehran) 2017;14:267-74.  Back to cited text no. 17
    
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Ghalayani P, Emami H, Pakravan F, Nasr Isfahani M. Comparison of triamcinolone acetonide mucoadhesive film with licorice mucoadhesive film on radiotherapy-induced oral mucositis: A randomized double-blinded clinical trial. Asia Pac J Clin Oncol 2017;13:e48-56.  Back to cited text no. 18
    
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Ismail AA, Behkite AA, Badria FM, Guemei AA. Licorice in prevention of radiation induced mucositis. J Clin Oncology 2004;22 Suppl 14:8268.  Back to cited text no. 19
    
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Hu CH, He J, Eckert R, Wu XY, Li LN, Tian Y, et al. Development and evaluation of a safe and effective sugar-free herbal lollipop that kills cavity-causing bacteria. Int J Oral Sci 2011;3:13-20.  Back to cited text no. 21
    
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Abstract
Introduction
Description of Plant
Chemical Constit...
Medicinal Uses
Commercial Uses
Role in Dentistry
Role of Glycy...
Conclusion
References

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