Horse chestnut - efficacy and safety in chronic venous insufficiency: an overview

Abstract

The extract from horse chestnut seeds (Aesculus hippocastanum L., Sapindaceae), standardised for the content of aescin, is used as the treatment for chronic venous insufficiency. It has anti-inflammatory and anti-oedematous properties and indicates a positive effect on the venous tone, Theological properties, and blood coagulability. The mechanism of horse chestnut seed extract/aescin activity was proposed on the basis of in vitro and in vivo studies, and its effectiveness was documented with numerous randomised clinical trials. The results of the studies have proven that horse chestnut seed extract not only significantly improves subjective symptoms in patients with chronic venous insufficiency like calf spasm, leg pain, pruritus, fatigue, but it also reduced leg volume, the ankle and calf circumference. The preparations containing horse chestnut seed extract are very popular and they have similar effectiveness as compression therapy and a preparation with 0-(β-hydroxyethyl)-rutosides. Moreover, horse chestnut seed extract has been proven to be safe and very well tolerated. The study was to present the results of the studies that have been conducted so far and that have confirmed the effectiveness of use of horse chestnut seed extract or aescin as the treatment for chronic venous insufficiency.

References

  1. Annoni, F., Mauri, A., Marincola, F., Resele, L.F., 1979. Venotonic activity of escin on the human saphenous vein. Arzneimittel-Forsch. 29, 672–675.

    CAS  Google Scholar 

  2. Arnould, T., Janssens, D., Michiels, C., Remade, J., 1996. Effect of aescine on hypoxia-induced activation of human endothelial cells. Eur. J. Pharmacol. 315, 227–233.

    CAS  PubMed  Google Scholar 

  3. Arnould, T., Michiels, C., Remade, J., 1993. Increased PMN adherence on endothelial cells after hypoxia: involvement of PAFCD18/CD11b, and ICAM-1. Am.J. Physiol. 264, 1102–1110.

    Google Scholar 

  4. Barnes, J., Anderson, L.A., Phillipson, J.D., 2007. Herbal Medicines, third ed. Pharmaceutical Press, London, Chicago, pp. 363–366.

    Google Scholar 

  5. Bisler, H., Pfeifer, R., Klüken, N., Pauschinger, P., 1986. Wirkung von Roβkastanien-samenextrakt auf die transkapilläre Filtrationbei chronisch venöser Insuffizienz. Deut. Med. Wochenschr. 111, 1321–1399.

    CAS  Google Scholar 

  6. Bougelet, C., Roland, L.H., Ninane, N., Arnould, T., Remacle, J., Michiels, C., 1998. Effect of aescine on hypoxiainduced neutrophil adherence to umbilical vein endothelium. Eur. J. Pharmacol. 345, 89–95.

    CAS  PubMed  Google Scholar 

  7. Cebo, B., Krupinska, J., Sobanski, H., Mazur, J., Czarnecki, R., 1976. Własnosci farmakologiczne frakcji saponinowych otrzymanych z surowców krajowych: Saponaria officinalis Primula officinalis, Aesculs hippocastanum. Herba. Polon. 22, 154–162.

    CAS  Google Scholar 

  8. Cesarone, M.R., Incandela, L., Belcaro, G., De Sanctis, M.T., Ricci, A., Griffin, M., 2001a. Two-week topical treatment with Essaven gel in patients with diabetic microangiopathy - a placebo-controlled, randomized study. Angiology 52 (Suppl. 3), 43–48.

    Google Scholar 

  9. Cesarone, M.R., De Sanctis, M.T., Incandela, L., Belcaro, G., Griffin, M., 2001b. Microvascular changes in venous hypertension due to varicose veins after standardized application of Essaven gel - a placebo-controlled, randomized study. Angiology 52 (Suppl. 3), 11–16.

    Google Scholar 

  10. Damas, P., Volon, G., Damas, J., 1976. Sur làtionantioedeme de elèscine. Bull. Soc. Roy. Sci. Liège 45, 436–442.

    CAS  Google Scholar 

  11. De Sanctis, M.T., Cesarone, M.R., Incandela, L., Belcaro, G., Griffin, M., 2001. Treatment of superficial vein thrombosis with standardized application of Essaven gel - a placebo-controlled, randomized study. Angiology 52 (Suppl. 3), 57–62.

    Google Scholar 

  12. Diehm, C., Schmidt, C., 2001. Venostasin retard gegen Plazebo und Kompression bei Patienten mit CVI II/IIIA. Final Study Report. Klinge Pharma GmbH Munich, Germany. Reported in: Ottillinger B et al. BMC Cardiovasc. Disord. 1, 5.

    Google Scholar 

  13. Diehm, C., Trampish, H.J., Lange, S., Schmidt, C., 1996. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet 347, 292–294.

    CAS  PubMed  Google Scholar 

  14. Diehm, C., Vollbrecht, D., Amendt, K., Comberg, H.U., 1992. Medical edema protection - clinical benefit in patients with chronic deep vein incompetence. VASA 21, 188–192.

    CAS  PubMed  Google Scholar 

  15. EMEA(European Medicines Agency), 2012. Science Medicines Health. EMEA, London http://www.ema.europa.eu (accessed November 2014).

    Google Scholar 

  16. Erdien, F., 1989. Klinische Wirksamkeit von Venostasin retard im Doppelblindversuch. Med. Welt. 40, 994–996.

    Google Scholar 

  17. Erler, M., 1991. Roβkastaniensamenextrakt bei der Therapie peripherer venöser Ödeme - ein klinischer Therapievergleich. Med. Welt 42, 593–596.

    Google Scholar 

  18. ESCOP Monographs, 2003. The Scientific Foundation for Herbal Medicinal Products, second ed. Thieme Publisher, Stuttgart, New York.

    Google Scholar 

  19. Facino, R.M., Carini, M., Stefani, R., Aldini, G., Saibene, L., 1995. Anti-Elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix Aesculus hippocastanum and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch. Pharm. 328, 720–724.

    CAS  Google Scholar 

  20. Felixsson, E., Persson, I.A.L., Eriksson, A.C., Persson, K., 2010. Horse chestnut extract contracts bovine vessels and affects human platelet aggregation through5-HT2A receptors: an in vitro study. Phytother. Res. 24, 1297–1301.

    CAS  PubMed  Google Scholar 

  21. Friederich, H.C., Vogelsberg, H., Neiss, A., 1978. Ein Beitrag zur Bewertung von intern wirksamen Venenpharmaka. Z. Hautkrankheiten. 53, 369–374.

    CAS  Google Scholar 

  22. Girerg, R.J., Di Pascquale, G., Steinetz, B.C., 1961. The anti-edema properties of aescin. Arch. Int. Pharmakodyn. 133, 127–137.

    Google Scholar 

  23. Guillaume, M., Padioleau, F., 1994. Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract. Arzneimittel-Forsch. 44, 25–35.

    CAS  Google Scholar 

  24. Incandela, L., Belcaro, G., Nicolaides, A.N., Geroulakos, G., Cesarone, M.R., De Sanctis, M.T., 2001. Microcirculation after standardized application of Essaven gel on normal skin - a placebo-controlled, randomized study. Angiology 52 (Suppl. 3), 5–10.

    Google Scholar 

  25. Kalbfleisch, W., Pfalzgraf, H., 1989. Ödemprotektiva Äquipotente Dosierung -Roβkastaniensamenextrakt und O-β-Hydroxyethylrutoside im Vergleich. Therapiewoche 39, 3703–3707.

    Google Scholar 

  26. Klemm, J., 1982. Strömungsgeschwindigkeit von Blut in varikösen Venen der unteren Extremitäten. Munchen. Med. Wochen 124, 579–582.

    CAS  Google Scholar 

  27. Koch, R., 2002. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother. Res. 16 (Suppl. 1), 1–5.

    Google Scholar 

  28. Liehn, H.D., Franco, P.A., Hampel, H., Hofrichter, G., 1972. A toxicological study of extractum Hippocastani semen (EHS). Panminerva Med. 14, 84–91.

    CAS  PubMed  Google Scholar 

  29. Lochs, H., Baumgartner, H., Konzett, H., 1974. Zur Beeinflussung des Venetonus durch Rosskastanienextrakte. Arzneimittel-Forsch. 24, 1347–1350.

    CAS  Google Scholar 

  30. Loew, D., Schrödter, A., Schwankl, W., März, R.W., 2000. Measurement of the bioavailability of aescin-containing extracts. Methods Find. Exp. Clin. Pharmacol. 22, 537–542.

    CAS  PubMed  Google Scholar 

  31. Lohr, E., Garanin, G., Jesau, P., Fischer, H., 1986. Ödempräventive Therapie bei chronischer Veneninsuffizienz mit Ödemneigung. Munchen. Med. Wochen. 128, 579–581.

    Google Scholar 

  32. Marshall, M., Dormandy, J.A., 1987. Oedema of long-distance flights. Phlebology 2, 123–124.

    Google Scholar 

  33. Matsuda, H., Li, Y., Murakami, T., Ninomiya, K., Araki, N., Yoshikawa, M., Yama-hara, J., 1997. Antiinflammatory effects of escins Ia, Ib, IIa, and IIb from horse chestnut the seeds of Aesculus hippocastanum L. Bioorg. Med. Chem. Lett. 7, 1611–1616.

    CAS  Google Scholar 

  34. Michiels, C., Arnould, T., Knott, L., Dieu, M., Remade, J., 1993. Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am. J. Physiol. 264, 866–874.

    Google Scholar 

  35. Neiss, A., Böhm, C., 1976. Zum Wirksamkeitsnachweis von Roβkastaniensamenex- trakt beim varikösen Symptomenkomplex. Munchen. Med. Wochen. 118, 213–216.

    CAS  Google Scholar 

  36. Panigati, D., 1992. The pharmacology of escin a saponin of Aesculus hippocastanum L. III. Pharmacokinetics and toxicology. Boll. Chim. Farm. 131, 320–321.

    CAS  PubMed  Google Scholar 

  37. Pauschinger, P., 1987. Klinisch experimentelle Untersuchungen zur Wirkung von Roβkastaniensamenextrakt auf die transkapilläre Filtration und das intravasale Volumen an Patienten mit chronisch venöser Insuffizienz. Phlebol. Proktol. 16, 57–61.

    Google Scholar 

  38. Piechal, A., Blecharz-Klin, K., Widy-Tyszkiewicz, E., 2005. Kasztanowiec zwyczajny (Aesculus hippocastani) we współczesnej terapii. Przew. Lek. 4, 74–81.

    Google Scholar 

  39. Pilz, E., 1990. Ödeme bei Venenerkrankungen. Med. Welt 41, 1143–1144.

    Google Scholar 

  40. Pittler, M.H., Ernst, E., 2012. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst. Rev., 11. Art. No.: CD003230. https://doi.org/10.1002/14651858.CD003230.pub4.

  41. Raffetto, J.D., Khalil, R.A., 2011. Ca(2+)-dependent contraction by the saponoside escin in rat vena cava: implications in venotonic treatment of varicose veins. J. Vasc. Surg. 54, 489–496.

    PubMed  PubMed Central  Google Scholar 

  42. Rehn, D., Unkauf, M., Klein, P., Jost, V., Lücker, P.W., 1996. Vergleich der klinischen Wirksamkeit und vertraglichkeit von oxerutin und Rosskastanien - extract bei patienten mit chronischer venoser Insuffizienz. Arzneimittel-Forsch. 46, 483–487.

    CAS  Google Scholar 

  43. Rudofsky, G., Neiss, A., Otto, K., Seibel, K., 1986. Ödemprotektive Wirkung und klinische Wirksamkeit von Roβkastaniensamenextrakt im Doppeltblindversuch. Phlebol. Proktol. 15, 47–54.

    Google Scholar 

  44. Sirtori, C.R., 2001. Aescin: pharmacology pharmacokinetics and therapeutic profile. Pharmacol. Res. 44, 183–193.

    CAS  PubMed  Google Scholar 

  45. Steiner, M., Hillemanns, H.G., 1990. Venostasin retard in the management of venous problems during pregnancy. Phlebology 5, 41–44.

    Google Scholar 

  46. Steiner, M., 1991. Ausmaβ der ödemprotektiven Wirkung von Roβkastaniensamenextrakt. VASA 20 (Suppl. 33), 217.

    Google Scholar 

  47. Sudoł-Szopińska, I., Błachowiak, K., Koziński, P., 2006. Wpływ czynników środowiskowych na rozwój przewlekłej niewydolności żylnej. Med. Pr. 57, 365–373.

    PubMed  Google Scholar 

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Acknowledgements

This work was supported by a research project of National Science Centre (NCN, Poland) (No. 2012/07/N/NZ7/02246). We would like to acknowledge Prof. Dr Hab. Wiesława Bylka (Department of Pharmacognosy, Poznan University of Medical Sciences, Poland) for her assistance and helpful comments on the manuscript.

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MD-M participated in data collection and writing of the manuscript. All the authors contributed to the critical reading and final editing of the manuscript.

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Correspondence to Marlena Dudek-Makuch.

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Dudek-Makuch, M., Studzińska-Sroka, E. Horse chestnut - efficacy and safety in chronic venous insufficiency: an overview. Rev. Bras. Farmacogn. 25, 533–541 (2015). https://doi.org/10.1016/j.bjp.2015.05.009

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Keywords

  • Aescin
  • Chronic venous insufficiency
  • Horse chestnut seeds