Comparison of the effect of ointment containing Citrus aurantium extract with phenytoin ointment on wound healing

Document Type : (original research)

Authors

1 Department of Veterinary Medicine, Babol Branch, Islamic Azad University, Babol, Iran

2 Department of Veterinary Medicine, Shabestar Branch, Islamic Azad University, Shabestar, Iran

3 Department of Veterinary Medicine, Garmsar Branch, Islamic Azad University, Garmsar, Iran

4 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

10.22034/AEJ.2022.317994.2699

Abstract

Increasing the speed of wound healing with the least scar tissue prevents wound infection and restores the integrity and health of the skin to normal. In this regard, medicinal plants with restorative effects have long been considered to prevent infection and rapid healing of superficial wounds. The aim of this study was to evaluate the wound healing after topical application of ointment containing Citrus aurantium extract (5%) in comparison with phenytoin ointment in rats. For this purpose, 32 adult rats were randomly divided into 4 groups, including negative control group, positive control group (without treatment), Citrus aurantium ointment treatment group (5%) and phenytoin ointment treatment group (1%). In this experiment, the skin of the lumbar region of mice was cut into 1 cm2 after anesthesia. Ointment containing Citrus aurantium extract and phenytoin ointment was applied topically twice a day for 14 days. Tissue samples were taken at 4, 7, 10 and 14 days after incision and microscopic images were obtained. Blood samples were taken from mice every 6 days to check the growth factor. On microscopic examination on the fourth day, budding tissue including fibroblast cell proliferation and developing blood vessels (angiogenesis) was observed in both treatment groups. On the seventh day, the bud tissue was less formed in the treated groups than in the control group. On the tenth day, the formation of epithelial tissue was observed in the group treated with Citrus aurantium extract as opposed to the group treated with phenytoin. On the fourteenth day, more collagen deposition and absence of inflammatory cells were observed in the group treated with Citrus aurantium extract than in the group treated with phenytoin. Growth factor levels were not significantly different in the study groups. Examination of microscopic images and measurement of wound shrinkage revealed that the group treated with spring orange extract had a higher percentage of improvement than the group treated with phenytoin, which was statistically significant (p<0.001). The results show that Citrus aurantium extract (5%) heals wounds faster than phenytoin ointment.

Keywords

Main Subjects


  1. Guo, S.A. and DiPietro, L.A., 2010. Factors affecting wound healing. J Dental Res. 89(3): 219-229.
  2. Mirbagheri, M.J. and Gholami-Ahangaran, M., 2021. The concurrent infection of Avibacterium paragalinarum and Escherichia coli in swollen head syndrome cases of layers in Isfahan province. Iran J Anim Environ. 13(4):
    97-102. (In Persian)
  3. Wannous, H., Lucas, Y. and Treuillet, S., 2010. Enhanced assessment of the wound-healing process by accurate multiview tissue classification. IEEE Trans Med Imaging. 30(2): 315-326.
  4. Abazari, M., Ghaffari, A., Rashidzadeh, H., Badeleh, S.M. and Maleki, Y.A., 2010. Systematic review on classification, identification, and healing process of burn wound healing. Int J Lower Ex Wounds. 15(3): 473-480. (In Persian)
  5. Bao, P., Kodra, A., Tomic-Canic, M., Golinko, M.S., Ehrlich, H.P. and Brem, H., 2009. The role of vascular endothelial growth factor in wound healing. J Surg Res. 153(2): 347-358.
  6. Ashcroft, G.S., Jeong, M.J., Ashworth, J.J., Hardman, M., Moutsopoulos, N. and Wahl, S.M., 2012. Tumor necrosis factor‐alpha (TNF‐α) is a therapeutic target for impaired cutaneous wound healing. Wound Rep Reg. 20(1): 38-49.
  7. Budovsky, A., Yarmolinsky, L. and Ben‐Shabat, S., 2015. Effect of medicinal plants on wound healing. Wound Rep Reg. 23(2): 171-183.
  8. Suntar, I., Khan, H., Patel, S., Celano, R. and Rastrelli, L., 2018. An overview on Citrus aurantium: Its functions as food ingredient and therapeutic agent. Oxidative Med Cell Longevity. 12(4): 100-110.
  9. Karthikeyan, V. and Karthikeyan, J., 2014. Citrus aurantium (bitter orange): A review of its traditional uses, phytochemistry and pharmacology. Int J Drug Dis Herbal Res. 4(4): 766-772.
  10. Fathi, H., Paknejad, S. and Ahanjan, M., 2017. Evaluating antimicrobial effects of different orange blossom extract (Citrus aurantium L) on microbial species in vitro. Health Biotech. Biopharma. 1: 25-36.
  11. Hajjar, T., Arhami, M. and Kakhki, M.V., 2019. Comparative Effects of Orange Blossom, Violet, and Marjoram Extracts and Lorazepam on Sleep Deprivation Induced Anxiety in Mice. Neurophysiol. 51(1): 29-34.
  12. Hamedi, A., Jamshidzadeh, A., Dana, M., Pasdaran, A. and Heidari, R., 2020. Investigation of the effect of essential oil from Citrus aurantium flowers on liver health parameters in a laboratory animal model. Kaums J (Feyz). 24(1): 38-47. (In Persian)
  13. Namazi, M., Akbari, S.A., Mojab, F., Talebi, A., Majd, H.A. and Jannesari, S., 2014. Aromatherapy with citrus aurantium oil and anxiety during the first stage of labor. Iran Red Cres Med J. 16(6): 100-110. (In Persian)
  14. Oluwatosin, O.M., Olabanji, J.K., Oluwatosin, O.A., Tijani, L.A. and Onyechi, H.U., 2000. A comparison of topical honey and phenytoin in the treatment of chronic leg ulcers. Afr J Med Med Sci. 29(1): 31-34.
  15. Bhatia, A. and Prakash, S., 2004. Topical phenytoin for wound healing. Derm Online J. 10(1): 100-110.
  16. Asadbegi, M., Mirazi, N., Vatanchian, M. and Gharib, A., 2016. Comparing the healing effect of Lotus Corniculatus Hydroethanolic Extract and phenytoin cream 1 on the rat's skin wound: A Morphometrical and Histopathological Study. J Chem Pharm Sci. 9(2): 746-752. (In Persian)
  17. Gomar, A., Hosseini, A. and Mirazi, N., 2014. Effect of Lotus Corniculatus Extracts on Wound Healing in Male Diabetic Rats Induced with Streptozocin. Med J Tabriz Uni Med Sci. 36(4): 94-101. (In Persian)
  18. Zeinali, M. and Sharifan, M., 2014. The restorative role of Zygophyllum eurypterum on wounds and skin inflammation, 2nd International Conference on New Findings in Agricultural Sciences, Resources and Environment, Tehran, Iran. (In Persian)
  19. Pourmahdi, O., Moshtagh, I., Rezvan, M. and Gholami Ahangaran, M., 2022. Comparison of the effect of citrus aurantium honey with phenytoin oint-ment on wound healing in rats. Iran J New Findings in Vet Microbiol. 4(2): 120-132. (In Persian)
  20. Bakhshayesh, M., Soleimani, M., Mehdizadeh, M. and Katebi, M., 2012. Effects of TGF-β and b-FGF on the potential of peripheral blood-borne stem cells and bone marrow-derived stem cells in wound healing in a murine model. Inflammation. 35(1): 138-142. (In Persian)
  21. Sharifian Paghaleh, M., Zeinali Pour, M. and Tavakkoli, M., 2013. The study of Zygophyllum eurypterum effects on wound healing process in Suri mice (Mus musculus). J Animal Environment. 7(3): 65-72. (In Persian)
  22. Najafi, N., Arabi, M and Jafarzadeh, H., 2014. Inducing effect of aloe vera gel extract on epithelial growth factor receptor gene expression in cutaneous wounds of male mice Balb/c. Cell Tissue. 5(1): 53-61. (In Persian)