The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.

2nd Department of Surgery Louise Pasteur University Hospital and Pavol Jozef Šafárik University 041 90 Košice Slovakia

BIOCEV Biotechnology and Biomedical Centre of The Czech Academy of Sciences and Charles University 1st Faculty of Medicine Charles University 252 50 Vestec Czech Republic

Department of Biomedical Research East Slovak Institute of Cardiovascular Diseases 040 11 Košice Slovakia

Department of Chemical Theory of Drugs Faculty of Pharmacy Comenius University 832 32 Bratislava Slovakia

Department of Experimental Medicine Faculty of Medicine Pavol Jozef Šafárik University 040 11 Košice Slovakia

Department of Human and Clinical Pharmacology University of Veterinary Medicine and Pharmacy 041 81 Košice Slovakia

Department of Natural Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences 612 42 Brno Czech Republic

Department of Pathology Louise Pasteur University Hospital 041 90 Košice Slovakia

Department of Pharmacognosy and Botany Faculty of Pharmacy Comenius University 832 32 Bratislava Slovakia

Department of Pharmacology Faculty of Medicine Pavol Jozef Šafárik University 040 11 Košice Slovakia

Institute of Anatomy 1st Faculty of Medicine Charles University 128 00 Prague Czech Republic

Laboratory of Cell Interactions Center of Clinical and Preclinical Research MediPark Pavol Jozef Šafárik University 040 11 Košice Slovakia

Prague Burn Centre 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady Charles University 100 34 Prague Czech Republic

Zobrazit více v PubMed

Reinke J.M., Sorg H. Wound repair and regeneration. Eur. Surg. Res. 2012;49:35–43. doi: 10.1159/000339613. PubMed DOI

Gal P., Varinska L., Faber L., Novak S., Szabo P., Mitrengova P., Mirossay A., Mucaji P., Smetana K. How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair. Molecules. 2017;22:1818. doi: 10.3390/molecules22111818. PubMed DOI PMC

Deonarine K., Panelli M.C., Stashower M.E., Jin P., Smith K., Slade H.B., Norwood C., Wang E., Marincola F.M., Stroncek D.F. Gene expression profiling of cutaneous wound healing. J. Transl. Med. 2007;5:11. doi: 10.1186/1479-5876-5-11. PubMed DOI PMC

Clark R.A., Ghosh K., Tonnesen M.G. Tissue engineering for cutaneous wounds. J. Invest. Dermatol. 2007;127:1018–1029. doi: 10.1038/sj.jid.5700715. PubMed DOI

Smetana Jr K., Szabo P., Gal P., Andre S., Gabius H.J., Kodet O., Dvorankova B. Emerging role of tissue lectins as microenvironmental effectors in tumors and wounds. Histol. Histopathol. 2015;30:293–309. doi: 10.14670/HH-30.293. PubMed DOI

Werner S., Krieg T., Smola H. Keratinocyte-fibroblast interactions in wound healing. J. Invest. Dermatol. 2007;127:998–1008. doi: 10.1038/sj.jid.5700786. PubMed DOI

Leach M.J., Pincombe J., Foster G. Clinical efficacy of horsechestnut seed extract in the treatment of venous ulceration. J. Wound. Care. 2006;15:159–167. doi: 10.12968/jowc.2006.15.4.26898. PubMed DOI

Fujimura T., Moriwaki S., Hotta M., Kitahara T., Takema Y. Horse chestnut extract induces contraction force generation in fibroblasts through activation of Rho/Rho kinase. Biol. Pharm. Bull. 2006;29:1075–1081. doi: 10.1248/bpb.29.1075. PubMed DOI

Braga P.C., Marabini L., Wang Y.Y., Lattuada N., Calo R., Bertelli A., Falchi M., Dal Sasso M., Bianchi T. Characterisation of the antioxidant effects of Aesculus hippocastanum L. bark extract on the basis of radical scavenging activity, the chemiluminescence of human neutrophil bursts and lipoperoxidation assay. Eur. Rev. Med. Pharmacol. Sci. 2012;16:1–9. PubMed

Vaskova J., Fejercakova A., Mojzisova G., Vasko L., Patlevic P. Antioxidant potential of Aesculus hippocastanum extract and escin against reactive oxygen and nitrogen species. Eur. Rev. Med. Pharmacol. Sci. 2015;19:879–886. PubMed

Fujimura T., Tsukahara K., Moriwaki S., Hotta M., Kitahara T., Takema Y. A horse chestnut extract, which induces contraction forces in fibroblasts, is a potent anti-aging ingredient. J. Cosmet. Sci. 2006;57:369–376. doi: 10.1111/j.1467-2494.2007.00369_3.x. PubMed DOI

Aksoy H., Cevik O., Sen A., Goger F., Sekerler T., Sener A. Effect of Horse-chestnut seed extract on matrix metalloproteinase-1 and -9 during diabetic wound healing. J. Food Biochem. 2019;43:e12758. doi: 10.1111/jfbc.12758. PubMed DOI

Sirtori C.R. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol. Res. 2001;44:183–193. doi: 10.1006/phrs.2001.0847. PubMed DOI

Gal P., Toporcer T., Vidinsky B., Mokry M., Novotny M., Kilik R., Smetana K., Jr., Gal T., Sabo J. Early changes in the tensile strength and morphology of primary sutured skin wounds in rats. Folia. Biol. (Praha.) 2006;52:109–115. PubMed

Hinz B. The role of myofibroblasts in wound healing. Curr. Res. Transl. Med. 2016;64:171–177. doi: 10.1016/j.retram.2016.09.003. PubMed DOI

Zhao S.Q., Xu S.Q., Cheng J., Cao X.L., Zhang Y., Zhou W.P., Huang Y.J., Wang J., Hu X.M. Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor. Chin. J. Nat. Med. 2018;16:105–112. doi: 10.1016/S1875-5364(18)30036-0. PubMed DOI

Novotny M., Vasilenko T., Varinska L., Smetana K., Jr., Szabo P., Sarissky M., Dvorankova B., Mojzis J., Bobrov N., Toporcerova S., et al. ER-alpha agonist induces conversion of fibroblasts into myofibroblasts, while ER-beta agonist increases ECM production and wound tensile strength of healing skin wounds in ovariectomised rats. Exp. Dermatol. 2011;20:703–708. doi: 10.1111/j.1600-0625.2011.01284.x. PubMed DOI

Gal P., Stausholm M.B., Kovac I., Dosedla E., Luczy J., Sabol F., Bjordal J.M. Should open excisions and sutured incisions be treated differently? A review and meta-analysis of animal wound models following low-level laser therapy. Lasers. Med. Sci. 2018;33:1351–1362. doi: 10.1007/s10103-018-2496-7. PubMed DOI

Abudayeh Z.H., Al Azzam K.M., Naddaf A., Karpiuk U.V., Kislichenko V.S. Determination of Four Major Saponins in Skin and Endosperm of Seeds of Horse Chestnut (Aesculus Hippocastanum L.) Using High Performance Liquid Chromatography with Positive Confirmation by Thin Layer Chromatography. Adv. Pharm Bull. 2015;5:587–591. doi: 10.15171/apb.2015.079. PubMed DOI PMC

Zhang L., Wang H., Wang T., Jiang N., Yu P., Liu F., Chong Y., Fu F. Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model. Exp. Ther. Med. 2012;3:735–739. doi: 10.3892/etm.2012.467. PubMed DOI PMC

Cheong D.H.J., Arfuso F., Sethi G., Wang L., Hui K.M., Kumar A.P., Tran T. Molecular targets and anti-cancer potential of escin. Cancer Lett. 2018;422:1–8. doi: 10.1016/j.canlet.2018.02.027. PubMed DOI

Elmowafy M., Shalaby K., Salama A., Soliman G.M., Alruwaili N.K., Mostafa E.M., Mohammed E.F., Moustafa A., Zafar A. Soy isoflavone-loaded alginate microspheres in thermosensitive gel base: Attempts to improve wound-healing efficacy. J. Pharm. Pharmacol. 2019;71:774–787. doi: 10.1111/jphp.13066. PubMed DOI

Varinska L., Faber L., Kello M., Petrovova E., Balazova L., Solar P., Coma M., Urdzik P., Mojzis J., Svajdlenka E., et al. beta-Escin Effectively Modulates HUVECS Proliferation and Tube Formation. Molecules. 2018;23:197. doi: 10.3390/molecules23010197. PubMed DOI PMC

Strnad H., Lacina L., Kolar M., Cada Z., Vlcek C., Dvorankova B., Betka J., Plzak J., Chovanec M., Sachova J., et al. Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes. Histochem. Cell. Biol. 2010;133:201–211. doi: 10.1007/s00418-009-0661-6. PubMed DOI

Brenmoehl J., Miller S.N., Hofmann C., Vogl D., Falk W., Scholmerich J., Rogler G. Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates their migration. World J. Gastroenterol. 2009;15:1431–1442. doi: 10.3748/wjg.15.1431. PubMed DOI PMC

Wong M., Mudera V. Feedback inhibition of high TGF-beta1 concentrations on myofibroblast induction and contraction by Dupuytren’s fibroblasts. J. Hand. Surg. Br. 2006;31:473–483. doi: 10.1016/J.JHSB.2006.05.007. PubMed DOI

Gal P., Toporcer T., Vidinsky B., Hudak R., Zivcak J., Sabo J. Simple interrupted percutaneous suture versus intradermal running suture for wound tensile strength measurement in rats: A technical note. Eur. Surg. Res. 2009;43:61–65. doi: 10.1159/000219214. PubMed DOI

Kovac I., Durkac J., Holly M., Jakubcova K., Perzelova V., Mucaji P., Svajdlenka E., Sabol F., Legath J., Belak J., et al. Plantago lanceolata L. water extract induces transition of fibroblasts into myofibroblasts and increases tensile strength of healing skin wounds. J. Pharm. Pharmacol. 2015;67:117–125. doi: 10.1111/jphp.12316. PubMed DOI

Assessment of Agrimonia eupatoria L. and Lipophosphonoxin (DR-6180) Combination for Wound Repair: Bridging the Gap Between Phytomedicine and Organic Chemistry

Novel lipophosphonoxin-loaded polycaprolactone electrospun nanofiber dressing reduces Staphylococcus aureus induced wound infection in mice

Human galectin‑3: Molecular switch of gene expression in dermal fibroblasts in vitro and of skin collagen organization in open wounds and tensile strength in incisions in vivo