Therapeutic effects of Glycyrrhiza glabra aqueous extract ointment on cutaneous wound healing in Sprague Dawley male rats

  • Akram Zangeneh
  • Mehrdad Pooyanmehr
  • Mohammad Mahdi ZangenehEmail author
  • Rohallah Moradi
  • Raheleh Rasad
  • Nastaran Kazemi
Original Article


Glycyrrhiza glabra has been reported to have wide applications in the treatment of many human diseases. However, its traditional use in the treatment of wounds has not been validated by any scientific study. Also, its safety in the management of cutaneous wound conditions requires attention. The purpose of the experiment was to investigate the wound healing potential of G. glabra aqueous extract ointment. In vivo design, 120 Sprague Dawley male rats were used. After creating the cutaneous wound, the animals were randomly divided into four groups: untreated control, treatment with Eucerin ointment, treatment with 3% tetracycline ointment, treatment with 3% G. glabra aqueous extract ointment (3 g of G. glabra aqueous extract + 97-g base ointment). At days 10, 20, and 30 after creating the wound, for histopathological and biochemical analysis of the cutaneous wound healing trend, a section was prepared from all dermal thicknesses. The data were analyzed using one-way ANOVA followed by Duncan post hoc test of SPSS-22 software. At days 10, 20, and 30, G. glabra aqueous extract ointment could significantly (p ≤ 0.05) decrease the level of the wound area, total cell, macrophage, lymphocyte, and neutrophil, and enhance the level of wound contracture, fibrocyte, hexuronic acid, and hydroxyproline as compared with the basal ointment and control groups. In conclusion, the present study has demonstrated that the aqueous extracts of G. glabra have properties that render them capable of promoting accelerated wound-healing activity compared with other groups.


Glycyrrhiza glabra Aqueous extract Cutaneous Wound healing 


Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.

Ethic approval

All institutional and national guidelines for the care and use of laboratory animals were followed.


  1. Anil K, Jyotsna D (2012) Review on Glycyrrhiza glabra. J Pharm Sci Innov 1(2):1–4Google Scholar
  2. Asl MN, Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 22(6):709–724CrossRefGoogle Scholar
  3. Azhdari-Zarmehri H, Nazemi S, Ghasemi E, Musavi Z, Tahmasebi Z, Farsad F, Farzam A (2014) Assessment of effect of hydro-alcoholic extract of Scrophularia Striata on burn healing in rat. JBUMS 16(5):42–48Google Scholar
  4. Bitter T, Muir HM (1962) A modified uronic acid carbazole reaction. Anal Biochem 4(4):330–334CrossRefGoogle Scholar
  5. Caetano GF, Fronza M, Leite MN, Gomes A, Frade MAC (2016) Comparison of collagen content in skin wounds evaluated by biochemical assay and by computer-aided histomorphometric analysis. Pharm Biol 54(11):2555–2559CrossRefGoogle Scholar
  6. Chen HJ, Kang SP, Lee IJ, Lin YL (2014) Glycyrrhetinic acid suppressed NF-kappaB activation in TNF-alpha-induced hepatocytes. J Agric Food Chem 62(3):618–625CrossRefGoogle Scholar
  7. Dastmalchi K, Damien DH, Oinonena P, Darwisd Y, Laaksoa I, Hiltunen R (2008) Chemical composition and in vitro antioscidative activity of a lemon balm (Melissa Officinaliss L.) extract. LWT Food Sci Technol 41:391–400CrossRefGoogle Scholar
  8. Dong Y-L, Fleming RYD, Yan TZ, Herndon DN, Waymack JP (1993) Effect of ibuprofen on the inflammatory response to surgical wounds. J Trauma 35(3):340–343CrossRefGoogle Scholar
  9. Dwivedi D, Dwivedi M, Malviya S, Singh V (2017) Evaluation of wound healing, anti-microbial and antioxidant potential of Pongamia pinnata in Wistar rats. J Tradit Complement Med 7(1):79–85CrossRefGoogle Scholar
  10. Foschi D, Trabucchi E, Musazzi M, Castoldi L, Di Mattia D, Radaelli E, Marazzi M, Franzini P, Berlusconi A (1988) The effects of oxygen free radicals on wound healing. Int J Tissue React 10(6):373–379Google Scholar
  11. Geethalakshmi R, Sakravarthi C, Kritika T, Arul Kirubakaran M, Sarada DVL (2013) Evaluation of antioxidant and wound healing potentials of Sphaeranthus amaranthoides Burm.f. Biomed Res Int 2013:607109–607107. CrossRefGoogle Scholar
  12. Ghashghaii A, Hashemnia M, Nikousefat Z, Zangeneh MM, Zangeneh A (2017) Wound healing potential of methanolic extract of Scrophularia striata in rats. Pharm Sci 23(4):256–263CrossRefGoogle Scholar
  13. Goorani S, Zangeneh MM, Koohi MK, Seydi N, Zangeneh A, Souri N, Hosseini MS (2018) Assessment of antioxidant and cutaneous wound healing effects of Falcaria vulgaris aqueous extract in Wistar male rats. Comp Clin Pathol 28:435–445. CrossRefGoogle Scholar
  14. Goorani S, Shariatifar N, Seydi N, Zangeneh A, Moradi R, Tari B, Nazari F, Zangeneh MM (2019) The aqueous extract of Allium saralicum 1 R.M. Fritsch effectively treat induced anemia. Experimental study on Wistar rats. Orient Pharm Exp Med.
  15. Guo S, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89(3):219–229CrossRefGoogle Scholar
  16. Hagh-Nazari L, Goodarzi N, Zangeneh MM, Zangeneh A, Tahvilian R, Moradi R (2017) Stereological study of kidney in streptozotocininduced diabetic mice treated with ethanolic extract of Stevia rebaudiana (bitter fraction). Comp Clin Pathol 26(2):455–463CrossRefGoogle Scholar
  17. Hamelian M, Zangeneh MM, Amisama A, Varmira K, Veisi H (2018) Green synthesis of silver nanoparticles using Thymus kotschyanus extract and evaluation of their antioxidant, antibacterial and cytotoxic effects. Appl Organomet Chem 32(9):e4458CrossRefGoogle Scholar
  18. Hemmati S, Rashtiani A, Zangeneh MM, Mohammadi P, Zangeneh A, Veisi H (2019) Green synthesis and characterization of silver nanoparticles using Fritillaria flower extract and their antibacterial activity against some human pathogens. Polyhedron 158:8–14CrossRefGoogle Scholar
  19. Hosseinkhani A, Falahatzadeh M, Raoofi E, Zarshenas MM (2016) An evidence-based review on wound healing herbal remedies from reports of traditional Persian medicine. J Evid Based Complementary Altern Med 22(2):334–343CrossRefGoogle Scholar
  20. Jalalvand AR, Zhaleh M, Goorani S, Zangeneh MM, Seydi N, Zangeneh A, Moradi R (2019) Chemical characterization and antioxidant, cytotoxic, antibacterial, and antifungal properties of ethanolic extract of Allium Saralicum R.M. Fritsch leaves rich in linolenic acid, methyl ester. J Photochem Photobiol B 192:103–112. CrossRefGoogle Scholar
  21. Khorasgni A, Karimi AH, Nazem MR (2010) A comparision of healing effects of propolis and silver sulfadia zine on full thickness skin wounds in rats. Pak Vet J 30(2):72–740Google Scholar
  22. Koh TJ, DiPietro LA (2011) Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med 13:e23CrossRefGoogle Scholar
  23. Kumar B, Vijaykumar M, Govindarajan R, Pushpangadan P (2008) Ethnopharmacological approaches to wound healing. Exploring medicinal plants of India. J Ethnopharmacol 12(8):103–110Google Scholar
  24. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC (1994) Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 130(4):489–493CrossRefGoogle Scholar
  25. Li YJ, Chen J, Li Y, Li Q, Zheng YF, Fu Y, Li P (2011) Screening and characterization of natural antioxidants in four Glycyrrhiza species by liquid chromatography coupled with electrospray ionization quadrupole time-offlight tandem mass spectrometry. J Chromatogr A 11:8181–8191CrossRefGoogle Scholar
  26. Liu H, Wang J, Zhou W, Wang Y, Yang L (2013) Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice. J Ethnopharmacol 146(3):773–793CrossRefGoogle Scholar
  27. Malekzadeh F (1986) Antimicrobial activity of Lawsonia inermis L. Appl Microbiol 16(4):663–664Google Scholar
  28. Montoro P, Maldini M, Russo M, Postorino S, Piacente S, Pizza C (2011) Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI/MS/MS and determination of major metabolites by LC-ESI/MS and LC-ESI/MS/MS. J Pharm Biomed Anal 54(3):535–544CrossRefGoogle Scholar
  29. Moradi R, Hajialiani M, Salmani S, Almasi M, Zangeneh A, Zangeneh MM (2018) Effect of aqueous extract of Allium saralicum R.M. Fritsch on fatty liver induced by high-fat diet in Wistar rats. Comp Clin Pathol.
  30. Mussel O, Saliva S, Costa A (2003) Mast cell in tissue response to density materials: an adhesive resin, a calcium hydroxide and a glass ionomer cement. J Cell Mol Med 7(2):171–173CrossRefGoogle Scholar
  31. Nayak BS, Isitor G, Davis EM, Pillai GK (2007) The evidence based wound healing activity of Lawsonia inermis Linn. Phytother Res 21(9):827–831CrossRefGoogle Scholar
  32. Oryan A, Tabatabaiei Naieni A, Moshiri A, Mohammadalipoor A, Tabandeh MR (2012) Modulation of cutaneous wound healing by Silymarin in rats. J Wound Care 21(9):457–464CrossRefGoogle Scholar
  33. Phillips GD, Whitehe RA, Kinghton DR (1991) Initiation and pattern of angiogenesis in wound healing in the rats. Am J Anat 192(3):257–262CrossRefGoogle Scholar
  34. Rezvanipour M, Pourzadehhosseini F, Malekpour R, Zarabi A (2007) The effect of mummy on some indices of wound healing in mice. J Kerman Univ Med Sci 14(4):77–267Google Scholar
  35. Robards K, Prenzler PD, Tucker G, Swatsitang P, Glover W (1999) Phenolic compounds and their role in oxidative processes in fruits. Food Chem 66(4):401–436CrossRefGoogle Scholar
  36. Sayyedrostami T, Pournaghi P, Ebrahimi Vosta-Kalaeea S, Zangeneh MM (2018) Evaluation of the wound healing activity of Chenopodium botrys leaves essential oil in rats (a short-term study). J Essent Oil Bear Pl 21(1):164–174CrossRefGoogle Scholar
  37. Sherkatolabbasieh H, Hagh-Nazari L, Shafiezadeh S, Goodarzi N, Zangeneh MM, Zangeneh A (2017) Ameliorative effects of the ethanolic extract of Allium saralicum R.M. Fritsch on CCl4-induced nephrotoxicity in mice: a stereological examination. Arch Biol Sci 69(3):535–543CrossRefGoogle Scholar
  38. Zangeneh MM, Goodarzi N, Zangeneh A, Tahvilian R, Najafi F (2018a) Amelioration of renal structural changes in STZ-induced diabetic mice with ethanolic extract of Allium saralicum R.M. Fritsch. Comp Clin Pathol 27(4):861–867CrossRefGoogle Scholar
  39. Zangeneh MM, Zangeneh A, Tahvilian R, Moradi R (2018b) Antidiabetic, hematoprotective and nephroprotective effects of the aqueous extract of Falcaria vulgaris in diabetic male mice. Arch Bio Sci 70(4):655–664CrossRefGoogle Scholar
  40. Zangeneh MM, Zangeneh A, Tahvilian R, Moradi R, Zhaleh H, Amiri-Paryan A, Bahrami E (2018c) Hepatoprotective and hematoprotective effects of Falcaria vulgaris aqueous extract against CCl4-induced hepatic injury in mice. Comp Clin Pathol 27:1359–1365. CrossRefGoogle Scholar
  41. Zhaleh M, Sohrabi N, Zangeneh MM, Zangeneh A, Moradi R, Zhaleh H (2018) Chemical composition and antibacterial effects of essential oil of Rhus coriaria fruits in the west of Iran (Kermanshah). J Essent Oil Bear Plant 21(2):493–501CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Science, Faculty of Veterinary MedicineRazi UniversityKermanshahIran
  2. 2.Biotechnology and Medicinal Plants Research CenterIlam University of Medical SciencesIlamIran
  3. 3.Department of Microbiology, Pathobiology & Basic Sciences, Faculty of Veterinary MedicineRazi UniversityKermanshahIran
  4. 4.School of Nursing and MidwiferyKermanshah University of Medical SciencesKermanshahIran
  5. 5.Department of ChemistryKermanshah Branch of ACECRKermanshahIran

Personalised recommendations