Wound healing activities of eucalyptol on full thickness excisional skin wound model in rats

Year 2026, Accepted Papers, 1 - 10

Mehmet Zeki Yılmaz Deveci , Ömer Kırgız , Hüseyin Özkan , Cafer Tayer İşler , Filiz Kazak Akçakavak , Ziya Yurtal , Akın Yakan

https://doi.org/10.33988/auvfd.1677537

Abstract

A plant-derived monoterpene, eucalyptol (1,8-cineole), has been suggested to have antioxidant, anti-inflammatory, and antimicrobial properties. The wound-healing effects of eucalyptol remain unknown. This study aimed to evaluate the topical use of eucalyptol at two concentrations on a full-thickness excisional skin wound model in terms of wound healing, gene expression, biochemical changes, and histopathological changes. Sixty Wistar rats were randomly divided into 5 groups (n = 12 per group). The control group (C) was untreated. Full-thickness excisional skin wounds were created in the following groups: the vehicle group (V), which was treated with polysorbate 80 solution (negative control). The Dexpanthenol group (D) was treated with dexpanthenol ointment (positive control). Eucalyptol 5% (E5) and Eucalyptol 10% (E10) groups were treated with 5% and 10% eucalyptol, respectively. Wound areas were measured on days 1, 4, 7, 11, 14, 18, and 21 days after wound creation. Wound tissues were collected on days 7 and 21. Histopathological, gene expression (TNFα, IL10, TGFβ1, VEGF), and biochemical (MDA, rGSH, GPx, CAT) analyses were performed on the wound tissues. TNFα gene expression levels were upregulated in Groups V and E5 (P<0.05). IL10 levels were upregulated in the V, E5, and E10 groups (P<0.05). TGFβ1 was upregulated in all groups compared with the control. Significant differences in rGSH, GPx, CAT, and MDA levels were found among all groups (P<0.05). Topical administration of 10% eucalyptol accelerates wound healing. With respect to epidermal thickness, 5% eucalyptol resulted in superior wound healing. Further studies should include different wound models, tissue analyses, and combinations of eucalyptol with other agents.

Keywords

cineole , cutaneous , dermatology , experimental , topical

Project Number

20.M.051

References

• Abramov Y, Golden B, Sullivan M, et al (2007): Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen, 15, 80-86.
• Aebi H (1984): Catalase. Methods Enzymol, 105, 121–126.
• Agyare C, Boakye YD, Bekoe EO, et al (2016): African medicinal plants with wound healing properties. J Ethnopharmacol, 177, 85-100.
• Akcakavak G, Kazak F, Deveci MZY (2023): Eucalyptol protects against cisplatin-induced liver injury in rats. Biol Bull, 50, 987-994.
• Akcakavak G, Kazak F, Karatas O, et al (2024): Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis. Toxicol Mech Methods, 34, 413-422.
• Albaayit SFA, Abba Y, Rasedee A, et al (2015): Effect of Clausena excavata Burm. f.(Rutaceae) leaf extract on wound healing and antioxidant activity in rats. Drug Des Devel Ther, 9, 3507-3518.
• Bahramsoltani R, Farzaei MH, Rahimi R (2014): Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review. Arch Dermatol Res, 306, 601-617.
• Beutler E (1975): Reduced Glutathione (GSH). 62-94. In: HV Bergmeyen (Ed), Red Blood Cell Metabolism: A Manual of Biochemical Methods. Grune and Stratton, New York.
• Bhowal M, Gopal M (2015): Eucalyptol: Safety and pharmacological profile. J Pharm Sci, 5, 125-131.
• Biswas TK, Pandit S, Chakrabarti S, et al (2017): Evaluation of Cynodon dactylon for wound healing activity. J Ethnopharmacol, 197, 128-137.
• Bozkaya E, Türk M, Ekici H, et al (2024): Investigation of the biocompatibility and in vivo wound healing effect of Cotinus coggygria extracts. Ankara Üniv Vet Fak Derg, 71, 269-280.
• Cetin EO, Yesil Celiktas O, Cavusoglu T, et al (2013): Incision wound healing activity of pine bark extract containing topical formulations: A study with histopathological and biochemical analyses in albino rats. Pharmazie, 68, 75-80.
• Dalkıran S, Yakan A, Özkan H (2025): Effects of melatonin on specific gene expression in the ovaries of superovulated rats. Ankara Üniv Vet Fak Derg, 72, 497-507.
• Deveci MZY, Enguven G, Ege H, et al (2024): Multifunctional hernia repair biopatch: Development, characterization, in vitro and in vivo evaluation. J Drug Deliv Technol, 100, 106132.
• Deveci MZY, Gönenci R, Canpolat İ, et al (2020): In vivo biocompatibility and fracture healing of hydroxyapatitehexagonal boron nitride-chitosan-collagen biocomposite coating in rats. Turk J Vet Anim Sci, 44, 76-88.
• Deveci MZY, İşler CT, Kırgız Ö (2022): Investigation of wound healing by infrared thermography in a full-thickness skin wound model in rats. J Appl Bio Sci, 16, 493-502.
• De Vincenzi M, Silano M, De Vincenzi A, et al (2002): Constituents of aromatic plants: eucalyptol. Fitoterapia, 73, 269-275.
• Ellman G (1959): Tissue sulphydryl groups. Arch Biochem Biophys, 82, 70–77.
• Ersel M, Uyanikgil Y, Akarca FK, et al (2016): Effects of silk sericin on incision wound healing in a dorsal skin flap wound healing rat model. Int J Exp Clin Res, 22, 1064-1078.
• Gałecka E, Jacewicz R, Mrowicka M, et al (2008): Antioxidative enzymes--structure, properties, functions. Pol Merkur Lek, 25, 266-268.
• Gillitzer R, Goebeler M (2001). Chemokines in cutaneous wound healing. J Leukoc Biol, 69, 513–521
• Gupta A, Singh RL, Raghubir R (2002): Antioxidant status during cutaneous wound healing in immunocompromised rats. Mol Cell Biochem, 241, 1-7.
• Han MC, Durmuş AS, Sağliyan A, et al (2017): Effects of Nigella sativa and Hypericum perforatum on wound healing. Turk J Vet Anim Sci, 41, 99-105.
• Hierner R, Degreef H, Vranckx JJ, et al (2005): Skin grafting and wound healing—the “dermato-plastic team approach”. Clin Dermatol, 23, 343-352.
• Izham MNM, Hussin Y, Rahim NFC, et al (2021): Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol. BMC Complement Med Ther, 21, 1-17.
• Karadsheh MJ, Nelson J, Wilcox R (2015): The application of skin adhesive to maintain seal in negative pressure wound therapy. Wounds, 27, 244–248.
• Kazak F, Akalın PP, Yarım GF, et al (2022): Protective effects of nobiletin on cisplatin induced neurotoxicity in rats. Int J Neurosci, 132, 531-537.
• Kazak F (2022): A bioactive compound: eucalyptol. In: Deveci HA (Ed), Functional foods and nutraceuticals: bioactive compounds. Livre de Lyon, Lyon.
• Kazak F, Deveci MZY, Akçakavak G (2024): Eucalyptol alleviates cisplatin-induced kidney damage in rats. Drug Chem Tox, 47, 172-179.
• Kırgız Ö, Altuğ ME, Özkan H, et al (2024): 45S5 Bioactive Glass-Ointment Positively Effects on Wound Healing in Rats by Regulating TNFα, Il-10, VEGF, and TGFβ. J Clin Lab Anal, 38, e25094.
• Kimmel AR, Brasaemle DL, McAndrews Hill M, et al (2010): Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res, 51, 468–471.
• Kumandaş A, Karslı B, Kürüm A, et al (2020):Comparison of the effects of zinc-silver cream and Nigella sativa oil on wound healing and oxidative stress in the wound model in rats. Ankara Univ Vet Fak Derg, 67, 33-40.
• Kumar B, Vijayakumar M, Govindarajan R, et al (2007): Ethnopharmacological approaches to wound healing—exploring medicinal plants of India. J Ethnopharmacol, 114, 103-113.
• Kurt B, Bilge N, Sözmen M, et al (2018): Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model. Biotech Histochem, 93, 249-257.
• Lee DD, Schwarz MA (2015): Adapted approach to profile genes while reconciling Vegf-a mRNA expression in the developing and injured lung. Am J Physiol Lung Cell Mol Physiol, 308, L1202-L1211. Livak KJ, Schmittgen TD (2001): Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25, 402-408.
• Lowry OH, Rosebrough NJ, Farr AL, et al (1951): Protein measurement with pholin phenol reagent. J Biol Chem, 193, 265–275.
• Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipit peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351–358.
• Okuda K, Murata M, Sugimoto M, et al (1998): TGF‐β1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA. J Oral Pathol Med, 27, 463–469.
• Özkan H, Kerman E (2020): Comparative evaluation of RNAlater solution and snap frozen methods for gene expression studies in different tissues. Rev Romana Med Lab, 28, 287-297.
• Ponrasu T, Jamuna S, Mathew A, et al (2013): Efficacy of L-proline administration on the early responses during cutaneous wound healing in rats. Amino acids, 45, 179-189.
• Rasik AM, Shukla A (2000): Antioxidant status in delayed healing type of wounds. Int J Exp Pathol, 81, 257-263.
• Rio DC, Ares M, Hannon GJ, et al (2010): Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protocols, 6, 5439.
• Saporito F, Sandri G, Bonferoni MC, et al (2018). Essential oil-loaded lipid nanoparticles for wound healing. Int J Nanomedicine, 13, 175-186.
• Sato Y, Ohshima T, Kondo, T, et al (1999): Regulatory role of endogenous interleukin-10 in cutaneous inflammatory response of murine wound healing. Biochem Biophys Res Commun, 265, 194-199.
• Schmid P, Cox D, Bilbe, G, et al (1993): TGF‐βs and TGF‐β type II receptor in human epidermis: differential expression in acute and chronic skin wounds. J Pathol, 171, 191-197.
• Schultz GS, Wysocki A (2009): Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen, 17, 153–162.
• Semiz N, Deveci MZY (2024): Effects of common centaury (Centaurium erythraea) oil and laurel (Laurus nobilis) seed oil on full-thickness excisional skin wound healing in rats. Ankara Univ Vet Fak Derg, 71, 487-496.
• Seol GH, Kim KY (2016): Eucalyptol and it’s role in chronic diseases. Adv Exp Med Biol, 929, 389-398.
• Soković M, Glamočlija J, Marin PD, et al (2010): Antibacterial effects of the essential oils of commonly consumed medicinal herbs using an in vitro model. Molecules, 15, 7532-7546.
• Stejskalová A, Almquist BD (2017): Using biomaterials to rewire the process of wound repair. Biomater Sci, 5, 1421- 1434.
• Şındak N, Akgül MB, Gülaydın A, et al (2017): Effects of topical terebinth berry oil and different experimental mixtures on wound healing in Japanese quails (Coturnix coturnix Japonica). Van Vet J, 28, 69-74.
• Wise LM, Stuart GS, Real NC, et al (2014): Orf virus IL‐ 10 accelerates wound healing while limiting inflammation and scarring. Wound Repair Regen, 22, 356-367.