Effect of Rosmarinic Acid in the Rat Experimental Wound Model
Abstract
Objective: The aim of this study was to investigate the effects of rosmarinic acid (RA) on wound healing using an experimental rat wound model, assessing collagen organization, inflammation, and epithelial regeneration.
Methods: Twenty-one rats were divided equally into three groups: Control, Wound, and Wound+RA. An wound was created on the dorsal skin of rats in the wound and wound+RA groups. Rosmarinic acid cream (10%) was applied daily to the wound+RA group for 14 days. Tissue samples were collected at the end of the experiment for histological (Masson Trichrome) and immunohistochemical (Cytokeratin 14, CK14) analyses.
Results: Histological evaluation showed significantly improved wound healing in the wound+RA group, characterized by organized collagen deposition, decreased inflammatory response, and enhanced epidermal regeneration compared to the wound group. Cytokeratin 14 immunostaining indicated increased CK14 expression, reflecting better epithelialization and keratinocyte differentiation in the RA-treated group.
Conclusion: Topical application of Rosmarinic Acid significantly improved wound healing by enhancing collagen organization, reducing inflammation, and promoting epithelial regeneration, suggesting potential clinical applications of Rosmarinic Acid in wound care management.
Keywords: rosmarinic acid, wound healing, CK14, immunohistochemistry
Keywords:
rosmarinic acid, wound healing, CK14, immunohistochemistryDOI
https://doi.org/10.22270/jddt.v15i4.7066References
1. Reinke J, Sorg H. Wound repair and regeneration. European surgical research. 2012;49(1):35-43. https://doi.org/10.1159/000339613 PMid:22797712
2. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological reviews. 2019;99(1):665-706. https://doi.org/10.1152/physrev.00067.2017 PMid:30475656 PMCid:PMC6442927
3. Cullen B, Smith R, Mcculloch E, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair and Regeneration. 2002;10(1):16-25. https://doi.org/10.1046/j.1524-475X.2002.10703.x PMid:11983003
4. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound repair and regeneration. 2009;17(6):763-771. https://doi.org/10.1111/j.1524-475X.2009.00543.x PMid:19903300 PMCid:PMC2810192
5. Hjort A, Gottrup F. Cost of wound treatment to increase significantly in Denmark over the next decade. Journal of wound care. 2010;19(5):173-184. https://doi.org/10.12968/jowc.2010.19.5.48046 PMid:20505590
6. Kloth LC. The roles of physical therapists in wound management, part II: patient and wound evaluation. The Journal of the American College of Certified Wound Specialists. 2009. https://doi.org/10.1016/j.jcws.2009.03.003 PMid:24527113 PMCid:PMC3478920
7. Oguntibeju OO. Medicinal plants and their effects on diabetic wound healing. Veterinary world. 2019;12(5):653. https://doi.org/10.14202/vetworld.2019.653-663 PMid:31327900 PMCid:PMC6584855
8. Liu J, Li X, Lin J, Li Y, Wang T, Jiang Q, Chen D. Sarcandra glabra (Caoshanhu) protects mesenchymal stem cells from oxidative stress: A bioevaluation and mechanistic chemistry. BMC Complementary and Alternative Medicine. 2016;16:1-10. https://doi.org/10.1186/s12906-016-1383-7 PMid:27793132 PMCid:PMC5084467
9. Fernando PMDJ, Piao MJ, Kang KA, Ryu YS, Hewage SRKM, Chae SW, Hyun JW. Rosmarinic acid attenuates cell damage against UVB radiation-induced oxidative stress via enhancing antioxidant effects in human HaCaT cells. Biomolecules & therapeutics. 2016;24(1):75. https://doi.org/10.4062/biomolther.2015.069 PMid:26759705 PMCid:PMC4703356
10. Martin R, Pierrard C, Lejeune F, Hilaire P, Breton L, Bernerd F. Photoprotective effect of a water-soluble extract of Rosmarinus officinalis L. against UV-induced matrix metalloproteinase-1 in human dermal fibroblasts and reconstructed skin. European Journal of Dermatology. 2008;18(2):128-135.
11. Nobile V, Michelotti A, Cestone E, Caturla N, Castillo J, Benavente-García O, et al. Skin photoprotective and antiageing effects of a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) polyphenols. Food & nutrition research. 2016;60(1):31871. https://doi.org/10.3402/fnr.v60.31871 PMid:27374032 PMCid:PMC4931025
12. Schweizer Jr, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, et al. New consensus nomenclature for mammalian keratins. The Journal of cell biology. 2006;174(2):169-174. https://doi.org/10.1083/jcb.200603161 PMid:16831889 PMCid:PMC2064177
13. Nelson WG, Sun T-T. The 50-and 58-kdalton keratin classes as molecular markers for stratified squamous epithelia: cell culture studies. The Journal of cell biology. 1983;97(1):244-251. https://doi.org/10.1083/jcb.97.1.244 PMid:6190820 PMCid:PMC2112495
14. Küba M, Türkoğlu A, Oğuz A, Tuncer M, Kaya Ş, Başol Ö, et al. Comparison of local rosmarinic acid and topical dexpanthenol applications on wound healing in a rat experimental wound model. Folia Morphologica. 2021;80(3):618-624. https://doi.org/10.5603/FM.a2020.0097 PMid:32844390
15. Hasanoglu A, Ara C, Ozen S, Kali K, Senol M, Ertas E. Efficacy of micronized flavonoid fraction in healing of clean and infected wounds. International Journal of Angiology. 2001;10:41-44. https://doi.org/10.1007/BF01616343 PMid:11178786
16. Turhan Y, Arıcan M, Karaduman ZO, Turhal O, Gamsızkan M, Aydın D, Ozkan K. Comparison of the effects of Nigella sativa oil and nano-silver on wound healing in an experimental rat model. Iran Red Crescent Med J. 2019;21:e84650. https://doi.org/10.5812/ircmj.84650
17. Firat A, Engin D, Ebru GO, Fırat Ş, Sezen EI. The Effect of Momordica charantia on Ovarian Ischemia-Reperfusion. Journal of Biosciences and Medicines. 2021;9(12):8-14. https://doi.org/10.4236/jbm.2021.912002
18. Kaplan Ö, Seyrek R, Soker S, Özdemir Başaran S, Aşır F, Deveci E, Şeker U. Effect of Aloe Vera On Mmp-1 And Timp-1 Expression on Diabetic Wound Healing. Journal of Cukurova Anesthesia and Surgical Sciences. 2023;6(2):204-209. https://doi.org/10.36516/jocass.1268067
19. Deveci B, Dağ A, Kadiroğlu ET, Aşır F, Gokalp-ozkorkmaz E, Deveci E. Alloplastik kemik grefti uygulanmış sıçan kalvarial kemik defekt modelinde rosmarinik asidin terapötik etkileri. Mersin Üniversitesi Sağlık Bilimleri Dergisi. 2022;15(1):88-99. https://doi.org/10.26559/mersinsbd.898835
20. Şahin F, Aşır F, Özkorkmaz EG, Başaran SÖ, Kaplan Ö, Ermiş IS, Deveci E. Investigation of the Effect of Rosmarinic Acid on Cyclophosphamide-Induced Gonadal Toxicity. Advances in Sexual Medicine. 2021;12(1):1-8. https://doi.org/10.4236/asm.2022.121001
21. Deveci E, Özkorkmaz EG, Aşır F, Şahin F, Ermiş IS, Ertaş A, et al. A histopathological comparison of prophylactic effects of Rosmarinic Acid and Oleanolic Acid isolated from Salvia species (sage) in scopolamine induced dementia model. J Drug Deliv Ther. 2021;11(6-S):37-42. https://doi.org/10.22270/jddt.v11i6-S.5129
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