Effect of Croton lechleri sap-based topical treatment, with or without nitroglycerin, on healing of equine metatarsal skin wounds.
Abstract: Skin wounds in horses, particularly in the distal extremities, often heal slowly due to mechanical stress, compromised perfusion, and excessive fibroplasia. This study evaluated the effects of topical Croton lechleri (CL) cream, alone or in combination with nitroglycerin, on the healing of skin wounds in the metatarsal region of horses. Six mares received six standardized wounds in each region and were treated with: saline solution, nitroglycerin (0.1 or 1 mg/mL), CL (1 or 10 µg/mL), or CL + nitroglycerin (10 µg/mL + 1 mg/mL). Wound contraction, histology, and bacterial culture were evaluated. Wounds treated with CL demonstrated increased collagen deposition and reduced angiogenesis over time. Nitroglycerin reduced vessel count over time in metatarsal wounds but did not significantly alter contraction. In conclusion, Croton lechleri appears to aid in tissue repair by modulating collagen deposition, angiogenesis, and inflammation.
© 2026 Published by Elsevier Ltd.
Publication Date: 2026-02-23 PubMed ID: 41810120PubMed Central: PMC12969322DOI: 10.1016/j.vas.2026.100598Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
Overview
- This study investigated how topical treatment with Croton lechleri (CL) sap, alone or combined with nitroglycerin, affects the healing process of skin wounds on the metatarsal area of horses.
- The research aimed to determine whether these treatments can improve wound healing by influencing physiological factors like collagen deposition, blood vessel formation, and inflammation in challenging wound locations.
Background
- Skin wounds in horses, especially on distal extremities such as the metatarsal region, often heal slowly. This is due to:
- Mechanical stress from movement and weight-bearing, which can disrupt healing tissues.
- Compromised perfusion, meaning limited blood flow to the area, restricting nutrients and oxygen needed for repair.
- Excessive fibroplasia, or overproduction of fibrous tissue, leading to abnormal scarring and delayed wound closure.
- Therefore, finding treatments that can optimize these healing factors is important to improve outcomes in equine wound care.
Objective and Experimental Design
- Researchers tested the effects of topical Croton lechleri, a plant sap known for its medicinal properties, on skin wound healing.
- They looked at:
- CL alone at two concentrations: 1 µg/mL and 10 µg/mL.
- Nitroglycerin alone at two concentrations: 0.1 mg/mL and 1 mg/mL. Nitroglycerin is a vasodilator that can increase blood flow.
- Combination treatment of CL (10 µg/mL) plus nitroglycerin (1 mg/mL).
- Saline solution as a control treatment.
- Six mares received six standardized skin wounds on each metatarsal region, with wounds assigned different treatments to compare outcomes.
Measured Outcomes
- Wound contraction: the amount of wound size reduction over time, indicating closure and healing progress.
- Histology: microscopic examination of tissue samples to assess:
- Collagen deposition, which is vital for strength and integrity of healed tissue.
- Angiogenesis, or new blood vessel formation, important for delivering nutrients but excessive angiogenesis may indicate prolonged inflammation or abnormal healing.
- Bacterial culture: to monitor infection status of wounds, as infection can delay healing.
Key Findings
- Wounds treated with Croton lechleri showed:
- Increased collagen deposition over time, suggesting enhanced formation of strength-providing tissue components.
- Reduced angiogenesis, indicating a possible modulation of inflammatory or repair processes that may avoid excess blood vessel formation and promote more organized healing.
- Nitroglycerin treatment resulted in:
- A reduction in vessel count over time, meaning fewer new blood vessels in the wounds. Although nitroglycerin is expected to increase blood flow initially, its effect here might be more complex in wound tissue.
- No significant effect on wound contraction, suggesting that although vascular changes occurred, they did not translate into measurable differences in wound closure rate during the study period.
- The combination of CL and nitroglycerin was also evaluated but the summary does not specify additive or synergistic effects beyond those of CL or nitroglycerin alone.
Conclusions and Implications
- Croton lechleri appears to aid tissue repair in equine metatarsal wounds by:
- Modulating collagen deposition, which is critical for rebuilding the dermal matrix and providing wound strength.
- Reducing angiogenesis, possibly leading to more controlled and efficient healing without excessive inflammation or scar tissue formation.
- Influencing inflammatory responses, which are intricately tied to wound healing processes.
- Nitroglycerin, while impacting vessel formation, did not significantly accelerate wound closure, suggesting its role may be limited or context-dependent in skin wound healing.
- These findings support the potential use of Croton lechleri sap-based topical treatments to improve wound healing in horses, especially in problematic distal extremity wounds.
- Further studies may be warranted to optimize dosing, evaluate long-term outcomes, and clarify combination therapy benefits.
Cite This Article
APA
Rosa MCB, Campos MEST, Albuquerque AS, Braz MS, Mapele RO, de Oliveira MCG, Toma HS, Ferraz PFP, Pereira RN, Raymundo DL.
(2026).
Effect of Croton lechleri sap-based topical treatment, with or without nitroglycerin, on healing of equine metatarsal skin wounds.
Vet Anim Sci, 32, 100598.
https://doi.org/10.1016/j.vas.2026.100598 Publication
Researcher Affiliations
- Centro Universitário de Lavras, UNILAVRAS, Caixa Postal 3141, CEP 37200-000, Lavras, MG, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
- Unidade de Estabilização de Fauna Marinha - Laboratório de Zoologia, Caixa postal 1873, CEP 88790-000, Laguna, SC, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
- Centro Universitário de Lavras, UNILAVRAS, Caixa Postal 3141, CEP 37200-000, Lavras, MG, Brasil.
- Universidade Federal de Uberlândia (UFU), Caixa Postal 593, CEP 38400-902, Uberlândia, MG, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
- Departamento de Medicina Veterinária, Universidade Federal de Lavras, UFLA, Campus Universitário, Caixa Postal 3037, CEP 37202-203, Lavras, MG, Brasil.
Conflict of Interest Statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
This article includes 32 references
- Anantama NA, Du Cheyne C, Martens A, Roth SP, Burk J, De Spiegelaere W, Michler JK. The granulation (t)issue: A narrative and scoping review of basic and clinical research of the equine distal limb exuberant wound healing disorder.. The Veterinary Journal 2022;280.
- Apaza Ticona L, Rumbero Sánchez Sánchez, Sánchez-Corral J, Iglesias Moreno P, Ortega Domenech M. Anti-inflammatory, pro-proliferative and antimicrobial potential of the compounds isolated from Daemonorops draco (Willd.) Blume.. Journal of Ethnopharmacology 2021:268.
- Boscarato AG, Orlandini CF, de Fátima Antunes Laginestra B, Pacheco FC, Jardim GF, de Oliveira JAB, Gazim ZC, Alberton LR. Use of Calender extract cream in equine lacerate wound.. Acta Scientiae Veterinariae 2020:48.
- Celeste CJ, Deschene K, Riley CB, Theoret CL. Regional differences in wound oxygenation during normal healing in an equine model of cutaneous fibroproliferative disorder.. Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society 2011;19(1):89–97.
- D’Agostino A, Adriana Pirozzi AV, Finamore R, Grieco F, Minale M, Schiraldi C. Molecular mechanisms at the basis of pharmaceutical grade triticum vulgare extract efficacy in prompting keratinocytes healing.. Molecules (Basel, Switzerland) 2020;25(3):431.
- de Albuquerque RDDG, León-Vargas FR, Carrasco-Montañez DD, Carranza-Gonzales JL, Ramos-Rivas YVS. A review on phytochemistry and recent pharmacology of Dragonʼs blood (Croton lechleri), a multifunctional ethnomedicinal resource from the Amazon Forest.. Planta Medica 2025;91(08):409–418.
- Dedar RK, Kumar N, Talluri TR, Singh J, Bhattacharya TK. Treatment of excessive growth of granulation tissue in horses by topical application of resveratrol.. Veterinary Record Case Reports 2025;13(1):e1089.
- Divakaran S, Loscalzo J. The role of nitroglycerin and other nitrogen oxides in cardiovascular therapeutics.. Journal of the American College of Cardiology 2017;70(19):2393–2410.
- Dubuc V, Lepault É, Theoret CL. Endothelial cell hypertrophy is associated with microvascular occlusion in horse wounds.. Canadian Journal of Veterinary Research 2006;70(3):206.
- Ellabban MA, Elmasry M, Abdelrahman I, Abdel Kader G, Steinvall I, Sjoberg F, Gomaa AA, Abdel Fattah IO. Experimental study of the effects of nitroglycerin, botulinum toxin A, and clopidogrel on bipedicled superficial inferior epigastric artery flap survival.. Scientific Reports 2022;12(1).
- Helal IE, Al-Abbadi HA, El-Daharawy MH, Ahmed MF. Enhancement of chronic wound healing with maltodextrin/ascorbic acid gel: A clinical evaluation of distal limb wounds in horses.. Journal of Animal Science and Technology 2022;64(5):997–1007.
- Labens R, Raidal S, Borgen-Nielsen C, Pyecroft S, Pant SD, De Ridder T. Wound healing of experimental equine skin wounds and concurrent microbiota in wound dressings following topical propylene glycol gel treatment.. Frontiers in Veterinary Science 2023;10.
- . Avaliação da ação cicatricial da seiva do Croton lechleri.. Dissertação de Mestrado – Universidade Federal de Pelotas – RS, Brazil. 2014.
- Magalhães MSF, Fechine FV, De Macedo RN, Monteiro DLS, Oliveira CC, Brito GADC, De Moraes MEA, De Moraes MO. Effect of a combination of medium chain triglycerides, linoleic acid, soy lecithin and vitamins A and E on wound healing in rats.. Acta Cirúrgica Brasileira 2008;23(3):262–269.
- Martins PS, Alves ALG, Hussni CA, Sequeira JL, Nicoletti JLM, Thomassian A. Comparação entre fitoterápicos de uso tópico na cicatrização de pele em eqüinos.. Archives of Veterinary Science 2003;8(2):1–7.
- Oliveira L.A.T., Souza V.R.C., Endringer D.C., Hendrickson D.A., Coelho C.S. Effects of topical application of sunflower-seed oil on experimentally induced wounds in horses. Journal of Equine Veterinary Science. 2012;32(3):139–145. doi: 10.1016/J.JEVS.2011.08.006.
- Peres I.S.A., Conceição K.A.O., Silva L.A.F., Khouri N.G., Yoshida C.M.P., Concha V.O.C., Lucarini M., Durazzo A., Santini A., Souto E.B., Severino P. Dragon’s blood: Antioxidant properties for nutraceuticals and pharmaceuticals. Rendiconti Lincei. Scienze Fisiche e Naturali. 2023;34(1):131–142. doi: 10.1007/S12210-022-01122-4. 2023 341.
- Perkins N.R., Reid S.W.J., Morris R.S. Profiling the New Zealand thoroughbred racing industry. 2. Conditions interfering with training and racing. New Zealand Veterinary Journal. 2005;53(1):69–76. doi: 10.1080/00480169.2005.36471;REQUESTEDJOURNAL:JOURNAL:TNZV20;PAGE:STRING:ARTICLE/CHAPTER.
- Pona A., Cline A., Kolli S.S., Taylor S.L., Feldman S.R. Review of future insights of Dragon’s Blood in dermatology. Dermatologic Therapy. 2019;32(2) doi: 10.1111/DTH.12786.
- Ramsey D.T., Pope E.R., Wagner-Mann C., Berg J.N., Swaim S.F. Effects of three occlusive dressing materials on healing of full-thickness skin wounds in dogs. American Journal of Veterinary Research. 1995;56(7):941–949. doi: 10.2460/AJVR.1995.56.07.941.
- Ribeiro G., Carvalho L., Borges J., Prazeres J. The best protocol to treat equine skin wounds by second intention healing: A scoping review of the literature. Animals. 2024;14(10):1500. doi: 10.3390/ANI14101500.
- Sá J.Z., Aguiar J.L.A., Cruz A.F., Schuler A.R.P., Lima J.R.A., Marques O.M. The effects of local nitroglycerin on the surgical delay procedure in prefabricated flaps by vascular implant in rats. Acta Cirúrgica Brasileira. 2012;27(12):905. doi: 10.1590/S0102-86502012001200013.
- Sørensen M.A., Petersen L.J., Bundgaard L., Toft N., Jacobsen S. Regional disturbances in blood flow and metabolism in equine limb wound healing with formation of exuberant granulation tissue. Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society. 2014;22(5):647–653. doi: 10.1111/WRR.12207.
- Sparks H.D., Sigaeva T., Tarraf S., Mandla S., Pope H., Hee O., Di Martino E.S., Biernaskie J., Radisic M., Scott W.M. Biomechanics of wound healing in an equine limb model: Effect of location and treatment with a peptide-modified collagen–Chitosan Hydrogel. ACS Biomaterials Science & Engineering. 2020;7(1):265–278. doi: 10.1021/ACSBIOMATERIALS.0C01431.
- Steinhorn B.S., Loscalzo J., Michel T. Nitroglycerin and nitric oxide — A rondo of themes in Cardiovascular therapeutics. New England Journal of Medicine. 2015;373(3):277–280. doi: 10.1056/NEJMSR1503311;ISSUE:ISSUE:DOI.
- Taylor P.M., Clarke K.W. Manual de anestesia. En equinos. 2009 Inter-Médica.
- Theoret C.L., Wilmink J.M. Aberrant wound healing in the horse: Naturally occurring conditions reminiscent of those observed in man. Wound Repair and Regeneration. 2013;21(3):365–371. doi: 10.1111/WRR.12018;CTYPE:STRING:JOURNAL.
- Wang P., Gu L., Qin Z., Wang Q., Ma J. Efficacy and safety of topical nitroglycerin in the prevention of mastectomy flap necrosis: A systematic review and meta-analysis. Scientific Reports. 2020;10(1):6753. doi: 10.1038/s41598-020-63721-1. 2020 101.
- Wang X., Gao Y., Sun X. Effect of Taspine hydrochloride on the repair of rat skin wounds by regulating keratinocyte growth factor signal. Bioengineered. 2022;13(1):789–799. doi: 10.1080/21655979.2021.2012920.
- Winter R.L., Tian Y., Caldwell F.J., Seeto W.J., Koehler J.W., Pascoe D.A., Fan S., Gaillard P., Lipke E.A., Wooldridge A.A. Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres. BMC Veterinary Research. 2020;16(1):43. doi: 10.1186/S12917-020-2269-Y. 2020 161.
- Wise L.M., Bodaan C.J., Stuart G.S., Real N.C., Lateef Z., Mercer A.A., Riley C.B., Theoret C.L. Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLOS ONE. 2018;13(5) doi: 10.1371/JOURNAL.PONE.0197223.
- Wise L.M., Stuart G.S., Sriutaisuk K., Adams B.R., Riley C.B., Theoret C.L. Anti-fibrotic actions of equine interleukin-10 on transforming growth factor-Beta1-stimulated dermal fibroblasts isolated from limbs of horses. Frontiers in Veterinary Science. 2020;7 doi: 10.3389/FVETS.2020.577835/FULL.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists