Home A Comparative evaluation of locally delivered licorice gel and tetracycline gel as an adjunct to non-surgical therapy in the treatment of controlled type −2 diabetic patients with periodontitis stage II and grade B – A split mouth randomized clinical trial
Article
Licensed
Unlicensed Requires Authentication

A Comparative evaluation of locally delivered licorice gel and tetracycline gel as an adjunct to non-surgical therapy in the treatment of controlled type −2 diabetic patients with periodontitis stage II and grade B – A split mouth randomized clinical trial

  • Mopati N. R. Gokul , Konathala S. V. Ramesh ORCID logo EMAIL logo , Penmetsa S. Gautami , Naga V. S. Sruthima ORCID logo , Mohankumar Pasupuleti and Venkatalakshmi Mathala
Published/Copyright: July 16, 2025

Abstract

Objectives

Periodontitis is an inflammatory disease affecting tooth-supporting structures due to dysbiosis in plaque bio-film. While NSPT remains the gold standard treatment, it limits in its capacity to fully eradicate pathogens, necessitating adjunct antimicrobial therapy. Local drug delivery(LDD) offers targeted treatment with fewer side effects compared to systemic antimicrobial therapy. Recent studies highlight herbal extracts, such as licorice (Glycyrrhiza glabra), which exhibit antimicrobial and anti-inflammatory properties, making them promising candidates for LDD. Therefore, the goal was to evaluate the effectiveness of licorice gel and tetracycline gel as a non-surgical treatment auxiliary for individuals with stage II periodontitis and grade B type-2 diabetes.

Methods

In this randomized, double-blind clinical trial, 20 patients with Type-II diabetes were included. Following NSPT, licorice and tetracycline gel were applied locally as adjuncts to both the test and control groups. Clinical parameters such as Probing pocket depth (PPD), Clinical attachment level (CAL), Bleeding on probing (BOP) were evaluated at base line and 1 month and Landry’s healing index at 7th day.

Results

In intergroup analysis, licorice gel has shown statistically significant reduction in PPD and CAL with better healing when compared to tetracycline gel.However, there was no statistically significant difference between the groups in terms of bleeding on probing.

Conclusions

Both licorice and tetracycline gel are equally effective in treating pockets but licorice gel as an LDD agent has shown better and encouragingoutcomes in terms of healing, PPD and CAL.


Corresponding author: Dr. Konathala S. V. Ramesh, MDS, Associate Professor, Department of Periodontics and Implantology, Vishnu dental college, Bhimavaram, 534202, Andhra Pradesh, India, E-mail:

  1. Research ethics: This study was conducted in the Department of Periodontology, Vishnu dental College, Andhra Pradesh, India. The study was approved by Institutional Ethical Committee (IECVDC/23/PG01/PI/IVV/114) and CTRI Trial Registration number for this trial is CTRI/2024/11/076956. All the patients were well informed and written informed consent was taken.

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: All other authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: All data generated or analyzed during this study are included in this published article.

References

1. Lima de Sousa, T, Dourado, D, Rodrigues, JS, de Souza Rebouças, J, Montes, MA, Formiga, FR. Treatment of periodontal disease: does drug delivery matter? Front Bioeng Biotechnol 2024;12:1427758. https://doi.org/10.3389/fbioe.2024.1427758.Search in Google Scholar PubMed PubMed Central

2. Zainuddin, SLA, Latib, N, Taib, H, Ahmad, B, Sabarudin, MA, Wan Mohamad, WM. Effectiveness of conventional periodontal treatment with tetracycline fiber versus Minocycline gel application subgingivally in periodontitis patients. Cureus 2024;16:e55167. https://doi.org/10.7759/cureus.55167.Search in Google Scholar PubMed PubMed Central

3. Grover, HS, Bhardwaj, A, Dadlani, H, Yadav, A, Singh, Y. Clinical evaluation of the efficacy of two commercially available controlled-release drugs-chlorhexidine gel (CHLO-SITE)TM and tetracycline fibers (periodontal plus AB)TM as an adjunct to scaling root planning in the treatment of chronic periodontitis. Eur J Gen Dent 2014;3:39–45. https://doi.org/10.4103/2278-9626.126209.Search in Google Scholar

4. Subramaniam, D, Pavithra, D. Local drug delivery in periodontics-a review. Eur J Mol Clin Med 2020;7:1874–81.Search in Google Scholar

5. Andrews, A, Shetti, N. Evaluation and comparison of antibacterial effects of a licorice gel and chlorhexidine gel on Porphyromonas gingivalis, aggregatibacter actinomycetamcomitans, and tannerella forsythia–an in vitro study. Indian J Health Sci Biomed Res kleu 2023;16:48–53. https://doi.org/10.4103/kleuhsj.kleuhsj1322.Search in Google Scholar

6. Sudhakar, U, Gethsie, KR, Priyanka, H, Zinneerah, SF. Local drug delivery drugs and systems. Int J Appl Decis Sci 2020;6:70–3. https://doi.org/10.22271/oral.2020.v6.i4b.1047.Search in Google Scholar

7. Agarwal, S, Nautiyal, A, Bali, S, Aggarwal, P, Garg, A. Local drug delivery systems for periodontal diseases-a review. J Pharm Negat Results 2022;16:1990–2.Search in Google Scholar

8. Sharma, NK, Prasad, A. Evaluation of efficacy of tetracycline as a local drug delivery system in the treatment of chronic periodontitis as an adjunct to scaling and root planing–a clinical and microbiological study. Int J Contemp Med Res 2017;4:998–1003.Search in Google Scholar

9. Ramesh, K, Joshna, I, Penmetsa, GS, Sruthima, GN, Kumar, PM, Anusha, B, et al.. Mangosteen peel extract vs tetracycline gel in treatment of periodontal abscess in Type-2 diabetes – a randomized clinical trial. J Dent Indones 2024;31:17–25. https://doi.org/10.14693/jdi.v30i3.1511.Search in Google Scholar

10. Ramesh, KSV, Gokul, MNR, Penmetsa, GS, Sruthima, GNVS, Mohan Kumar, P, Swetha, P, et al.. Quantitative determination of the antibacterial activity of licorice (Glycyrrhiza glabra) and tetracycline gel against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (pg) and Prevotella intermedia (pi) – a microbiological in vitro study. J Compl Integr Med 2024;22:142–8. https://doi.org/10.1515/jcim-2024-0183.Search in Google Scholar PubMed

11. Susanto, C, Ervina, I, Agusnar, H. In vitro evaluation of antimicrobial effectiveness chitosan based tetracycline gel on some pathogenic periodontal bacteria. IntJ Appl Dent Sci. 2017;3:71–6.Search in Google Scholar

12. Chopra, I, Roberts, M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001;65:232–60. https://doi.org/10.1128/mmbr.65.2.232-260.2001.Search in Google Scholar PubMed PubMed Central

13. Khan, SF, Shetty, B, Khan, AM, Fazal, I. Formulation and in-vitro characterization of herbal licorice gel for periodontal therapy. J Res Pharm 2022;26:1037–51.10.29228/jrp.202Search in Google Scholar

14. AlDehlawi, H, Jazzar, A. The power of licorice (Radix glycyrrhizae) to improve oral health: a comprehensive review of its pharmacological properties and clinical implications. Healthcare 2023;11:2887. https://doi.org/10.3390/healthcare11212887.Search in Google Scholar PubMed PubMed Central

15. Long, DR, Mead, J, Hendricks, JM, Hardy, ME, Voyich, JM. 18β-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Chemother 2013;57:241–7. https://doi.org/10.1128/aac.01023-12.Search in Google Scholar PubMed PubMed Central

16. Chandrasekaran, CV, Deepak, HB, Thiyagarajan, P, Kathiresan, S, Sangli, GK, Deepak, M, et al.. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products. Phytomedicine 2011;18:278–84. https://doi.org/10.1016/j.phymed.2010.08.001.Search in Google Scholar PubMed

17. Yeh, CF, Wang, KC, Chiang, LC, Shieh, DE, Yen, MH, San Chang, J. Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol 2013;148:466–73. https://doi.org/10.1016/j.jep.2013.04.040.Search in Google Scholar PubMed PubMed Central

18. Singh, V, Pal, A, Darokar, MP. A polyphenolic flavonoid glabridin: oxidative stress response in multidrug-resistant Staphylococcus aureus. Free Radic Biol Med 2015;87:48–57. https://doi.org/10.1016/j.freeradbiomed.2015.06.016.Search in Google Scholar PubMed

19. Li, S, Zhu, JH, Cao, LP, Sun, Q, Liu, HD, Li, WD, et al.. Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line. Neurol Sci 2014;35:1115–20. https://doi.org/10.1007/s10072-014-1661-4.Search in Google Scholar PubMed

20. Dhingra, D, Sharma, A. Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests. Prog Neuro Psychopharmacol Biol Psychiatr 2006;30:449–54. https://doi.org/10.1016/j.pnpbp.2005.11.019.Search in Google Scholar PubMed

21. Michel, HE, Tadros, MG, Abdel-Naim, AB, Khalifa, AE. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines. Neurosci Lett 2013;544:110–4. https://doi.org/10.1016/j.neulet.2013.03.055.Search in Google Scholar PubMed

22. Sharifzadeh, M, Shamsa, F, Shiran, S, Karimfar, MH, Miri, AH, Jalalizadeh, H, et al.. A time course analysis of systemic administration of aqueous licorice extract on spatial memory retention in rats. Planta Med 2008;74:485–90. https://doi.org/10.1055/s-2008-1074494.Search in Google Scholar PubMed

23. Sharma, G, Kar, S, Palit, S, Das, PK. 18β-glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells. J Cell Physiol 2012;227:1923–31. https://doi.org/10.1002/jcp.22920.Search in Google Scholar PubMed

24. Su, WPM, Voon Chen Yong, P, Viseswaran, N, Chia, YY. Estrogenicity of glabridin in Ishikawa cells. PLoS One 2015;10:e0121382. https://doi.org/10.1371/journal.pone.0121382.Search in Google Scholar PubMed PubMed Central

25. Jin, Z, Kim, S, Cho, S, Kim, IH, Han, D, Jin, YH. Potentiating effect of glabridin on GABAA receptor-mediated responses in dorsal raphe neurons. Planta Med 2013;79:1408–12. https://doi.org/10.1055/s-0033-1350698.Search in Google Scholar PubMed

26. Shivprasad, BM, Sonali, C, Navnita, S, Shilpa, S, Sruthi, KN, Savita, S. Liquorice as an adjunct to scaling and root planing in the treatment of chronic periodontitis: a clinico-microbiological study. Int J Sci Res 2017;6:73–6.Search in Google Scholar

27. Pant, VA, Maurya, DK, Nigam, M. Non-surgical periodontal therapy in severe chronic periodontitis patients associated with type II diabetes mellitus: a case report. IP Int J PeriodontolImplantol 2022;7:23–6. https://doi.org/10.18231/j.ijpi.2022.005.Search in Google Scholar

28. Sinha, S, Kumar, S, Dagli, N, Dagli, RJ. Effect of tetracycline HCl in the treatment of chronic periodontitis–A clinical study. J Int Soc Prev Community Dent 2014;4:149–53. https://doi.org/10.4103/2231-0762.142011.Search in Google Scholar PubMed PubMed Central

29. Nadig, PS, Shah, MA. Tetracycline as local drug delivery in treatment of chronic periodontitis: a systematic review and meta-analysis. J Indian Soc Periodontol 2016;20:576–83. https://doi.org/10.4103/jisp.jisp9717.Search in Google Scholar

30. Toshniwal, P, Mudda, JA, Desai, S, Aniketh, R, Jain, S. Comparative evaluation of local drug delivery using tetracycline fibers and antimicrobial photodynamic therapy in stage II grade B periodontitis: a clinico-microbiological study. J Indian Soc Periodontol 2024;28:664–72. https://doi.org/10.4103/jisp.jisp20924.Search in Google Scholar

31. Jeong, SN, Han, SB, Lee, SW, Magnussen, I. Effects of tetracycline-containing gel and a mixture of tetracycline and citric acid-containing gel on non-surgical periodontal therapy. J Periodontol 1994;65:840–7. https://doi.org/10.1902/jop.1994.65.9.840.Search in Google Scholar PubMed

32. Gandrakota, K, Sethuraman, S, Jayakumari, NK, Vidyadhar, KN. Subgingival delivery of bifidobacterium gel versus tetracycline gel as an adjunct to scaling and root Planing-A randomized controlled trial. J Young Pharm 2024;16:578–85. https://doi.org/10.5530/jyp.2024.16.72.Search in Google Scholar

33. George, RP, Kumar, S, Ramakrishna, T, Emmadi, P, Ambalavanan, N. Effects of tetracycline-containing gel and a mixture of tetracycline and citric acid-containing gel on non-surgical periodontal therapy. Indian J Dent Res 2013;24:52–9. https://doi.org/10.4103/0970-9290.114949.Search in Google Scholar PubMed

34. Walker, BR, Edwards, CR. Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol Metab Clin N Am 1994;23:359–77. https://doi.org/10.1016/s08898529-18301026.Search in Google Scholar

35. Omar, HR, Komarova, I, El-Ghonemi, M, Fathy, A, Rashad, R, Abdelmalak, HD, et al.. Licorice abuse: time to send a warning message. Ther Adv Endocrinol Metab 2012;3:125–38. https://doi.org/10.1177/2042018812454322.Search in Google Scholar PubMed PubMed Central

36. Murphy, SC, Agger, S, Rainey, PM. Too much of a good thing: a woman with hypertension and hypokalemia. Clin Chem 2009;55:2093–6. https://doi.org/10.1373/clinchem.2009.127506.Search in Google Scholar PubMed

37. Farhad, SZ, Aminzadeh, A, Mafi, M, Barekatain, M, Naghney, M, Ghafari, MR. The effect of adjunctive low-dose doxycycline and licorice therapy on gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis. Dent Res J 2013;10:624–9.Search in Google Scholar

38. Kedia, S, Vaishnav, K, Metri, R, Giri, TG, Shelke, UM, Deshpande, S. Clinical efficacy of mulethi (Glycyrrhiza glabra) gel in the management of localized aggressive periodontitis: a randomized controlled trial. Libr Prog-Libr Sci, Information Technol Comput 2024;44:14904–8.Search in Google Scholar

39. Kumar, YB, Gupta, D, Kumar Thakur, R, Chauhan, J, Mishra, R, Kumar, A. Assessment of the efficacy of subgingivally delivered liquorice gel on clinical parameters and prostaglandin E2 levels in chronic periodontitis: a clinico-biochemical study. Cureus 2025;17:e76781. https://doi.org/10.7759/cureus.76781.Search in Google Scholar PubMed PubMed Central

40. Sharma, S, Sogi, GM, Saini, V, Chakraborty, T, Sudan, J. Effect of liquorice (root extract) mouth rinse on dental plaque and gingivitis – a randomized controlled clinical trial. J Indian Soc Periodontol 2022;26:51–7. https://doi.org/10.4103/jisp.jisp-517-20.Search in Google Scholar

41. Jain, P, Sontakke, P, Walia, S, Yadav, P, Biswas, G, Kaur, D. Assessment of the efficacy of licorice versus 0.2% chlorhexidine oral rinse on plaque-induced gingivitis: a randomized clinical trial. Indian J Oral Health Res 2017;3:15–18. https://doi.org/10.4103/ijohr.ijohr-18-17.Search in Google Scholar

42. Ali, A, Mohammed, R. The Iraqi method of natural liquorice as a mouth rinse and its effect in patient with chronic periodontitis. Iraqi Dent J. 2016;38:43–7. https://doi.org/10.26477/idj.v38i1.72.Search in Google Scholar

43. Madan, S, Kashyap, S, Mathur, G. Glycyrrhiza glabra: an efficient medicinal plant for control of periodontitis – a randomized clinical trial. J Int Clin Dent Res Organ 2019;11:32–5. https://doi.org/10.4103/jicdro.jicdro719.Search in Google Scholar

44. Hamdon, SM, Ghada, Y, Rahman, A. Glycyrrhiza glabara as antibacterial agent on biofilm and planktonic cell of Aggre-gatibacter actinomycetemcomitans. Int J Dent Sci Res 2014;2:42–6.10.12691/ijdsr-2-2-4Search in Google Scholar

45. Salehi, M, Saeedi, M, Ehsani, H. Analyzing Glycyrrhiza glabra (licorice) extract efficacy in recurrent aphthous stomatitis recovery. J Res Med Dent Sci 2018;6:68–75.Search in Google Scholar

46. Suwannakul, S, Chaibenjawong, P. Antibacterial activities of Glycyrrhiza glabra linn. (licorice) root extract against por-phyromonas gingivalis and its inhibitory effects. J Dent Indones 2017;24:85–92. https://doi.org/10.14693/jdi.v24i3.1075.Search in Google Scholar

47. Bodet, C, La, VD, Gafner, S, Bergeron, C, Grenier, D. A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood. J Periodontol 2008;79:1752–61. https://doi.org/10.1902/jop.2008.080052.Search in Google Scholar PubMed

48. Sasaki, H, Suzuki, N, Alshwaimi, E, Xu, Y, Battaglino, R, Morse, L, et al.. 18β-Glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor‐κB inactivation in interleukin‐10‐deficient mice. J Periodontal Res 2010;45:757–63. https://doi.org/10.1111/j.1600-0765.2010.01296.x.Search in Google Scholar PubMed PubMed Central

49. LaVD, TSI, Bergeron, C, Gafner, S, Grenier, D. Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan a: potential therapeutic approach for periodontitis. J Periodontol 2011;82:122–8. https://doi.org/10.1902/jop.2010.100342.Search in Google Scholar PubMed

50. Khan, SF, Shetty, B, Fazal, I, Khan, AM, Mir, FM, Moothedath, M, et al.. Licorice as a herbal extract in periodontal therapy. Drug Target Insights 2023;17:70–7. https://doi.org/10.33393/dti.2023.2583.Search in Google Scholar PubMed PubMed Central

51. Li, J, Lee, YS, Choi, JS, Sung, HY, Kim, JK, Lim, SS, et al.. Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking akt activation and TGF-Beta signaling. Phytomedicine 2010;17:800–10. https://doi.org/10.1016/j.phymed.2010.02.004.Search in Google Scholar PubMed

52. Mohammad, G, Siddiquei, MM, Othman, A, Al-Shabrawey, M, El-Asrar, AM. High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina. Exp Eye Res 2013;107:101–9. https://doi.org/10.1016/j.exer.2012.12.009.Search in Google Scholar PubMed

53. Yang, L, Jiang, Y, Zhang, Z, Hou, J, Tian, S, Liu, Y. The anti-diabetic activity of licorice, a widely used Chinese herb. J Ethnopharmacol 2020;263:113216. https://doi.org/10.1016/j.jep.2020.113216.Search in Google Scholar PubMed

54. Karthikeson, PS, Laxmi, T. Anti-diabetic activity of glycyrrhiza glabra-An in vitro study. Int J Pharmaceut Sci Rev Res 2017;44:80–1.Search in Google Scholar

55. Kataya, HH, Hamza, AA, Ramadan, GA, Khasawneh, MA. Effect of licorice extract on the complications of diabetes nephropathy in rats. Drug Chem Toxicol 2011;34:101–8. https://doi.org/10.3109/01480545.2010.510524.Search in Google Scholar PubMed

56. Jaroszewski, J, Mamun, N, Czaja, K. Bidirectional interaction between tetracyclines and gut microbiome. Antibiot (Basel) 2023;12:1438. https://doi.org/10.3390/antibiotics12091438.Search in Google Scholar PubMed PubMed Central

57. Shin, YW, Bae, EA, Lee, B, Lee, SH, Kim, JA, Kim, YS, et al.. In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components. Planta Med 2007;73:257–61. https://doi.org/10.1055/s-2007-967126.Search in Google Scholar PubMed

58. Bethapudi, B, Murugan, SK, Nithyanantham, M, Singh, VK, Agarwal, A, Mundkinajeddu, D. Chapter 24 – gut health benefits of licorice and its flavonoids as dietary supplements. In: Bagchi, D, editor. Ohia Metabolism and Immune Health SEBT-N and FF in BD. London: Elsevier Publications; 2022:377–417 pp.10.1016/B978-0-12-821232-5.00008-2Search in Google Scholar

59. Wu, SC, Yang, ZQ, Liu, F, Peng, WJ, Qu, SQ, Li, Q, et al.. Antibacterial effect and mode of action of flavonoids from licorice against methicillin-resistant Staphylococcus aureus. Front Microbiol 2019;10:2489. https://doi.org/10.3389/fmicb.2019.02489.Search in Google Scholar PubMed PubMed Central

60. Bangert, K, Kluger, MA, Kluge, S, Janneck, M. Life-threatening complications of excessive licorice consumption. Dtsch Arztebl Int 2021;118:890–1. https://doi.org/10.3238/arztebl.m2021.0390.Search in Google Scholar PubMed PubMed Central

Received: 2024-12-04
Accepted: 2025-06-24
Published Online: 2025-07-16

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 9.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jcim-2024-0434/html
Scroll to top button