Effectiveness of Licorice Extract (Glycyrrhiza glabra L.) on Traumatic Ulcer with Parameter Study: Macrophage, Neutrophil, and Lymphocyte

Liftia Layyinatus Syifa*    -  Faculty of Dentistry, Sultan Agung Islamic University, Indonesia
Rina Kartika Sari    -  Faculty of Dentistry, Sultan Agung Islamic University, Indonesia
Dea Maynur Shalima Ismail  -  Faculty of Dentistry, Sultan Agung Islamic University, Indonesia
Rizqila Diva Pradisha  -  Faculty of Dentistry, Sultan Agung Islamic University, Indonesia

(*) Corresponding Author

Background: Traumatic oral ulcers are common lesions characterized by epithelial loss, pain, and erythematous halos. Healing occurs through four stages: haemostasis, inflammation, proliferation, and remodelling. Licorice root (Glycyrrhiza glabra L.) is known for its anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the effectiveness of licorice extract at various concentrations on macrophage, neutrophil, and lymphocyte cell counts during traumatic ulcer healing.

MethodsA post-test only group design was used with five groups: three treatment groups receiving 5%, 10%, and 15% licorice extract, and two control groups (positive: Aloclair; negative: aquadest), each with six mice. Ulcers were induced using a heated burnisher on the labial mucosa. Treatments were applied twice daily using a nano mouth spray. After euthanasia, labial tissues were fixed, processed, and stained with Hematoxylin-Eosin for histological examination under 400× magnification.

ResultPhytochemical analysis revealed high flavonoid (44.669) and saponin (38.802) contents in licorice extract. Statistical tests showed significant differences (p < 0.05) in macrophage, neutrophil, and lymphocyte counts among groups. The 10% extract group showed the highest immune cell response, suggesting optimal anti-inflammatory and immunomodulatory effects at this concentration.

Conclusion: Licorice extract effectively promotes the healing of traumatic oral ulcers. Among tested concentrations, the 10% extract provided the best therapeutic effect, accelerating healing and regulating inflammatory cell activity more effectively than other doses or controls.

Keywords: Traumatic ulcer, macrophage, neutrophil, lymphocyte

  1. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Elsevier; 2020.
  2. Dhinesh Kumar S, Vadivel JK, Ramanathan V. Role of topical anesthetics versus topical steroids in the management of traumatic ulcer: A case control study. Int J Res Pharm Sci. 2020;11(Special Issue 3):1446–51.
  3. Kallarakkal TG, Sekar K. Ulceration Related to New Dentures: Traumatic Ulcer. In: Clinicopathological Correlation of Oral Diseases. 2023. p. 371–80.
  4. Polonowita A, Guan G. Traumatic Oral Ulceration. In: Oral Medicine-A Clinical Guide. 2023. p. 209–11.
  5. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: A case report and review of the literature. Br Dent J. 2010;208(7):297–300.
  6. Hassan MAA. Histological and Histomorphomitrical Evaluation of Rabbit Oral Cavity Wound Healing by Feeding Absorbable Amino Acid. Diyala J Med. 2024;27(2):77–90.
  7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: A cellular perspective. Physiol Rev. 2019;99(1):665–706.
  8. Mill SJ, Hofma BR, Cowin AJ. Pathophysiology of Wound Healing. In: Mechanisms of Vascular Disease: A Textbook for Vascular Specialists, Third Edition. 2020. p. 541–61.
  9. Macleod AS, Kwock JT. Inflammation in Wound Repair: Role and Function of Inflammation in Wound Repair. In: Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects. 2018. p. 177–94.
  10. Zheremyan EA, Ustiugova AS, Karamushka NM, Uvarova AN, Stasevich EM, Bogolyubova A V, et al. Breg-Mediated Immunoregulation in the Skin. Int J Mol Sci. 2024;25(1).
  11. Scully C, Porter S. Oral mucosal disease: Recurrent aphthous stomatitis. Br J Oral Maxillofac Surg. 2008;46(3):198–206.
  12. Wagner VP, Webber LP, Ortiz L, Rados P V, Meurer L, Lameira OA, et al. Effects of Copaiba Oil Topical Administration on Oral Wound Healing. Phyther Res. 2017;31(8):1283–8.
  13. Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP. Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phyther Res. 2018;32(12):2325–39.
  14. Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phyther Res. 2008;22(6):709–24.
  15. Titiek Berniyanti, Mohammad Iqbal, Naufal Ikbar Yaasir, Fernando Rizky Ashifudin Pasha Mulyana, Abdullah Sherf Hemadi. Anti-inflammatory ability of licorice (Glycyrrhiza glabra) root extract in cyclooxygenase-2 enzyme inhibition: In silico study. World J Adv Res Rev. 2024;21(1):1798–804.
  16. Hanafi N, Talebpour Amiri F, Shahani S, Enayatifard R, Ghasemi M, Karimpour AA. Licorice cream promotes full-thickness wound healing in Guinea pigs. Marmara Pharm J. 2018;22(3):411–21.
  17. Assar DH, Elhabashi N, Mokhbatly AAA, Ragab AE, Elbialy ZI, Rizk SA, et al. Wound healing potential of licorice extract in rat model: Antioxidants, histopathological, immunohistochemical and gene expression evidences. Biomed Pharmacother. 2021;143.
  18. Wang D, Calabrese EJ, Lian B, Lin Z, Calabrese V. Hormesis as a mechanistic approach to understanding herbal treatments in traditional Chinese medicine. Pharmacol Ther. 2018;184:42–50.
  19. Calabrese EJ, Agathokleous E, Kapoor R, Kozumbo WJ, Rattan SIS. Re-analysis of herbal extracts data reveals that inflammatory processes are mediated by hormetic mechanisms. Chem Biol Interact. 2019;314.
  20. Srivastava V, Dhiman VK, Pandey A, Verma SK, Singh D. Harnessing the medicinal potential of herbs through hormesis: Perspectives in global health and therapeutics. Food Chem Adv. 2025;7.
  21. Chen HD, Zhao LH, Shen JG, Wang YS, Xu GL, Tong XL. Present situation and deliberation of the dose-effect relationship of prescriptions and herb medicines. Chinese J New Drugs. 2014;23(20):2424–9.
  22. Lakhdhir FAH, Alauddin U, ul Haq E, Qadir F. BEYOND THE PLEASURE PRINCIPLE - FATAL CARDIAC ARRHYTHMIAS AFTER INGESTION OF AN HERBAL MEDICATION. J Ayub Med Coll. 2022;34(4):874–6.
  23. Sharifi-Rad J, Quispe C, Herrera-Bravo J, Belén LH, Kaur R, Kregiel D, et al. Glycyrrhiza Genus: Enlightening Phytochemical Components for Pharmacological and Health-Promoting Abilities. Oxid Med Cell Longev. 2021;2021.
  24. Petrosyan HR, Nigaryan AA, Hovhannisyana HA, Soloyan M, Vardapetyan V V, Martiryan AI. ENVIRONMENTAL SAFETY AND ANTIOXIDANT POTENTIAL OF LICORICE ROOT HARVESTED IN PENZA. Oxid Commun. 2024;47(3):478–85.
  25. Fatima I, Sahar A, Tariq A, Naz T, Usman M. Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-κB and MAPK. J Nutr Metab. 2024;2024(1).
  26. Babich O, Ivanova S, Ulrikh E, Popov A, Larina V, Frolov A, et al. Study of the Chemical Composition and Biologically Active Properties of Glycyrrhiza glabra Extracts. Life. 2022;12(11).
  27. Aly SH, Elissawy AM, Mahmoud AMA, El-Tokhy FS, Mageed SSA, Almahli H, et al. Synergistic Effect of Sophora japonica and Glycyrrhiza glabra Flavonoid-Rich Fractions on Wound Healing: In Vivo and Molecular Docking Studies. Molecules. 2023;28(7).
  28. Chiba S, Hisamatsu T, Suzuki H, Mori K, Kitazume MT, Shimamura K, et al. Glycolysis regulates LPS-induced cytokine production in M2 polarized human macrophages. Immunol Lett. 2017;183:17–23.
  29. Liu Z, Zhong JY, Gao EN, Yang H. [Effects of glycyrrhizin acid and licorice flavonoids on LPS-induced cytokines expression in macrophage]. Zhongguo Zhong Yao Za Zhi. 2014;39(19):3841–5.
  30. Ahmadi P, Taherkhani S, Honardoost M, Janzadeh A. Flavonoids and macrophage polarization: Key players in the immunomodulation of cardiometabolic syndrome and related therapies. PharmaNutrition. 2025;33.
  31. Wu Y, Zhu J, Liu H, Liu H. Licochalcone A improves the cognitive ability of mice by regulating Tand B-cell proliferation. Aging (Albany NY). 2021;13(6):8895–915.
  32. Phan HTL, Kim HJ, Jo S, Kim WK, Namkung W, Nam JH. Anti-inflammatory effect of licochalcone a via regulation of ORAI1 and K+ channels in T-Lymphocytes. Int J Mol Sci. 2021;22(19).
  33. Nie M, Li Y, Huang X, Cheng T, Zhao Q. Activities of polysaccharides in combination with aluminum adjuvant in varicella-zoster subunit vaccines. Chinese J Microbiol Immunol. 2019;39(6):454–9.
  34. Ayeka PA, Bian YH, Githaiga PM, Zhao Y. The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice. BMC Complement Altern Med. 2017;17(1).

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