InteractionsGuide Index Page
Analysis Search Terms:
Horse Chestnut
Botanical Name: Aesculus hippocastanum L.
Pharmacopoeial Name: Hippocastani semen.
Common Names: Horse chestnut, chestnut.
Family
Sapindaceae (classified in Hippocastanaceae until 1998).
Parts Used
Seeds.
The bark and leaf of the tree are separate remedies, little used today. 1,2
Common Forms
- Tincture: Fresh or dried seed, 65% alcohol.
- Standardized Extract: Horse chestnut standardized extract (HCSE)—5:1 to 8:1 standardized to 16% to 20% triterpene glycosides, tablets or capsules (Aesculoforce, Bioforce AG; Venostat, Pharmaton Natural Health Products).
- Topical: Ointments, gels containing extracts at 2% aescin.
Strategic Considerations
Horse chestnut preparations have been popular in Europe for several decades, used for a variety of conditions of the venous system, both chronic (venous insufficiency, varicosities, hemorrhoids, leg ulcers, and edema) and acute (postoperative and posttraumatic edema, including elevated intracranial pressure, traumatic hematoma, contusions, and soft tissue swelling; sports injuries, especially involving edema). Aesculus seed is well described by Weiss 3 under diseases of the venous system and has monographs by the German Commission E 4 (1994, revised from an earlier unapproved monograph of leaf and flower in 1984), World Health Organization (WHO) in 2002, and European Scientific Cooperative on Phytotherapy (ESCOP) in 2003, as well as a recent literature review by McKenna et al. 7 Clinical trials for horse chestnut in chronic venous insufficiency (CVI) have been subjected to meta-analysis for the Cochrane database by Pittler and Ernst, 8 who found positive evidence for short-term efficacy in treating CVI.
Pharmacological attention has focused on the activity of the triterpene saponin fraction, a complex mixture of triterpenoids usually described as escin (aescin), which has venoactive anti-inflammatory and antiedematous properties, with some in vitro antioxidant, antiproliferative, and immunomodulatory activities. 9,10Available controlled clinical trials (13 total, 8 placebo controlled) of HCSE for venous insufficiency were systematically reviewed by Pittler and Ernst, 11 who concluded HCSE was safe, effective, and superior to placebo for short-term treatment of CVI. European use has also involved parenteral preparations of aescin (sodium escinate) and extensive use of a proprietary topical product Essaven which is a combination of aescin with pharmaceutical ingredients, heparin and phospholipids.
The monographs by German Commission E 4 and ESCOP 6 list no known interactions between horse chestnut seed and pharmaceutical drugs. (See, however, the later precaution regarding gentamicin from WHO.) Interactions reports in the literature are lacking. Positive clinical reports and trials of the topical combination product Essaven since the 1970s suggest a potential benefit of the combination in a wide range of conditions, and this is therefore accorded the status of a beneficial interaction (heparin + phospholipid; see later). Earlier European studies provide some basis for considering a potentially beneficial interaction with corticosteroid therapy; this is also assigned a potential interaction status here despite a lack of recent data. Speculative interactions include warfarin and hypoglycemics. Pharmacokinetic data are not currently available, and effects on drug-metabolizing enzymes, if any, have not been established.
Amikacin (Amikin), gentamicin (G-mycin, Garamycin, Jenamicin), kanamycin (Kantrex), neomycin (Mycifradin, Myciguent, Neo-Fradin, NeoTab, Nivemycin), netilmicin (Netromycin), paromomycin (monomycin; Humatin), streptomycin, tobramycin (AKTob, Nebcin, TOBI, TOBI Solution, TobraDex, Tobrex).
WHO 5 suggests a potential interaction based on a report of nephrotoxicity after excessive doses of aescin with gentamicin. The report, dating from 1978, involved a combination of aescin, an IV preparation of purified saponin compounds, with the known nephrotoxic antibiotic gentamicin. 46 McKenna et al. 7 cite an earlier Italian report by Grasso and Corvaglia 47 (text and abstract unavailable for inspection) of two cases of toxic nephropathy associated with high dose of aescin (i.e., intoxication), not interaction. These two cases both involved IV saponin fraction in the clinical context of acute postsurgical edema. Sirtori 10 reports that at the time of these warnings of potential nephrotoxicity, three trials examined the renal function in 83 patients who had preexisting kidney disease and in healthy volunteers who received 10 mg IV aescin per day. No worsening of renal impairment in the renal patients or effect on the healthy individuals was noted.
- 1.Wichtl M. Hippocastani cortex. In: Bisset NG, ed. Herbal Drugs and Phytopharmaceuticals. Boca Raton. Fla: CRC Press; 1994:268-270.
- 2.Wichtl M. Hippocastani folium. In: Bisset NG, ed. Herbal Drugs and Phytopharmaceuticals. Boca Raton, Fla: CRC Press; 1994:271-272.
- 3.Weiss R. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield , UK: Beaconsfield Publishers Ltd; 1988.
- 4.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
- 5.WHO. Semen Hippocastani. WHO Monographs on Selected Medicinal Plants. 2 vol. Geneva: World Health Organization; 2002:137-148.
- 6.ESCOP. Hippocastani Semen. ESCOP Monographs: the Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:248-256.
- 7.McKenna D, Jones K, Hughes K, Humphrey S. Horse chestnut. Botanical Medicines. 2nd ed. Binghamton, NY: Haworth Press; 2002:677-694.
- 8.Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2006:CD003230.View Abstract
- 9.Bombardelli E, Morazzoni P, Griffini A. Aesculus hippocastanum L. Fitoterapia 1996;67:483-511.
- 10.Sirtori CR. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res 2001;44:183-193.View Abstract
- 11.Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency: a criteria-based systematic review. Arch Dermatol 1998;134:1356-1360.View Abstract
- 12.Preziosi P, Manca P. [Research on the corticomimetic activity of escin]. Boll Soc Ital Biol Sper 1964;40 Suppl:1940-1943.View Abstract
- 13.Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone; 2000.
- 14.Put TR. [Advances in the conservative treatment of acute traumatic cerebral edema: controlled clinical trial with follow-up examination (author’s translation)]. Munch Med Wochenschr 1979;121:1019-1022.
- 15.Heppner F, Ascher WP, Argyropoulus G. [Current observations on the effect of aescin in neurosurgery]. Wien Med Wochenschr 1967;117:706-709.View Abstract
- 16.Xiao G-m, Wei J. Effects of beta-aescin on the expression of nuclear factor-kappa B and tumor necrosis factor-alpha after traumatic brain injury in rats. J Zhejiang Univ Sci B 2005;6:28-32.
- 17.Kunz K, Lorkowski G, Petersen G et al. Bioavailability of escin after administration of two oral formulations containing Aesculus extract. Arzneimittelforschung 1998;48:822-825.View Abstract
- 18.Loew D, Schrodter A, Schwankl W, Marz RW. Measurement of the bioavailability of aescin-containing extracts. Methods Find Exp Clin Pharmacol 2000;22:537-542.View Abstract
- 19.Schrader E, Schwankl W, Sieder C, Christoffel V. [Comparison of the bioavailability of beta-aescin after single oral administration of two different drug formulations containing an extract of horse-chestnut seeds]. Pharmazie 1995;50:623-627.View Abstract
- 20.Rothhaar J, Thiel W. [Percutaneous gel therapy of blunt athletic injuries]. Med Welt 1982;33:1006-1010.View Abstract
- 21.Crielaard JM, Franchimont P. [Value of using Reparil gel in sports traumatology]. Acta Belg Med Phys 1986;9:287-298.View Abstract
- 22.Arslanagic I, Brkic N. [Personal experience in the treatment of acute sports injuries with Essaven gel]. Med Arh 1982;36:205-208.View Abstract
- 23.Zuinen C. [Tolerance for and efficacy of the gel 1328 AN in sports injuries]. Rev Med Liege 1976;31:169-174.View Abstract
- 24.Rocco P. [Evaluation of the effectiveness of treatment with phlebotropic drugs, using dynamic telethermography]. Minerva Med 1980;71:2071-2078.View Abstract
- 25.Tozzi E, Scatena M, Castellacci E. [Anti-inflammatory local frigotherapy with a combination of escin, heparin and polyunsaturated phosphatidylcholine (EPL)]. Clin Ter 1981;98:517-524.View Abstract
- 26.Wojcicki J, Samochowiec L, Lawczynski L, Dabrowski Z. Local treatment of thrombophlebitis with Essaven gel. Arch Immunol Ther Exp (Warsz) 1976;24:807-810.View Abstract
- 27.Tolino A. [Medical treatment of the anorectal varicose syndrome in gynecology and obstetrics]. Minerva Ginecol 1979;31:169-174.View Abstract
- 28.Malin L, Pollinzi V. [Therapeutic activity of a new topical preparation in ano-rectal varicose pathology]. G Clin Med 1978;59:521-529.View Abstract
- 29.Nappi R. [A new non-corticoid preparation with an escin base in topical treatment of the ano-rectal varicose syndrome]. Clin Ter 1978;86:219-228.View Abstract
- 30.Bertrand GL. [Experimental study of beta-aescine (1) gel in oral and periodontal surgery]. Rev Odontostomatol Midi Fr 1981;39:211-216.View Abstract
- 31.Calabrese C, Preston P. Report of the results of a double-blind, randomized, single-dose trial of a topical 2% escin gel versus placebo in the acute treatment of experimentally induced hematoma in volunteers. Planta Med 1993;59:394-397.View Abstract
- 32.Incandela L, De Sanctis MT, Cesarone MR et al. Treatment of superficial vein thrombosis: clinical evaluation of Essaven gel—a placebo-controlled, 8-week, randomized study. Angiology 2001;52 Suppl 3:S69-72.View Abstract
- 33.De Sanctis MT, Cesarone MR, Incandela L et al. Treatment of superficial vein thrombophlebitis of the arm with Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S63-67.View Abstract
- 34.De Sanctis MT, Cesarone MR, Incandela L et al. Treatment of superficial vein thrombosis with standardized application of Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S57-62.View Abstract
- 35.Incandela L, Belcaro G, Nicolaides AN et al. Microcirculation after standardized application of Essaven gel on normal skin—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S5-10.View Abstract
- 36.De Sanctis MT, Cesarone MR, Incandela L et al. Four-week treatment with Essaven gel in diabetic microangiopathy—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S49-55.View Abstract
- 37.Cesarone MR, Incandela L, Belcaro G et al. Two-week topical treatment with Essaven gel in patients with diabetic microangiopathy—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S43-48.View Abstract
- 38.Incandela L, Belcaro G, Cesarone MR et al. Microvascular alterations in diabetic microangiopathy: topical treatment with Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S35-41.View Abstract
- 39.De Sanctis MT, Incandela L, Belcaro G, Cesarone MR. Topical treatment of venous microangiopathy in patients with venous ulceration with Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S29-34.View Abstract
- 40.Incandela L, Belcaro G, Cesarone MR et al. Changes in microcirculation in venous ulcers with Essaven gel—a pilot, cross-over, placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S23-27.View Abstract
- 41.Incandela L, Belcaro G, Cesarone MR et al. Microangiopathy and venous ulceration: topical treatment with Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S17-21.View Abstract
- 42.Cesarone MR, De Sanctis MT, Incandela L et al. Microvascular changes in venous hypertension due to varicose veins after standardized application of Essaven gel—a placebo-controlled, randomized study. Angiology 2001;52 Suppl 3:S11-16.View Abstract
- 43.Belcaro G, Nicolaides AN, Geroulakos G et al. Essaven gel—review of experimental and clinical data. Angiology 2001;52 Suppl 3:S1-4.View Abstract
- 44.Saenko VF, Sukharev, II, Viktorov AP, Goloopykho LI. [Experience with the clinical use of Essaven gel in treating venous diseases]. Klin Khir 1996:13-14.
- 45.Wilhelm K, Feldmeier C. [Thermometric investigations about the efficacy of beta-escin to reduce postoperative edema (author’s translation)]. Med Klin 1977;72:128-134.
- 46.Voigt E, Junger H. [Acute posttraumatic renal failure following therapy with antibiotics and beta-aescin (author’s translation)]. Anaesthesist 1978;27:81-83.
- 47.Grasso A, Corvaglia E. [Two cases of a suspected toxic tubulunephrosis due to escine]. Gazetta Medica Italiana 1976;135:581-584.
- 48.Yoshikawa M, Harada E, Murakami T et al. Escins Ia, Ib, IIa, IIb, and IIIa, bioactive triterpene oligoglycosides from the seeds of Aesculus hippocastanum L.: their inhibitory effects on ethanol absorption and hypoglycemic activity on glucose tolerance test. Chem Pharm Bull (Tokyo) 1994;42:1357-1359.View Abstract
- 49.Matsuda H, Murakami T, Li Y et al. Mode of action of escins Ia and IIa and E,Z-senegin II on glucose absorption in gastrointestinal tract. Bioorg Med Chem 1998;6:1019-1023.View Abstract
- 50.Harkness R, Bratman S. Mosby’s Handbook of Drug-Herb and Drug-Supplement Interactions. St Louis: Mosby; 2003.
- 51.Sekiya K, Okuda H, Arichi S. Selective inhibition of platelet lipoxygenase by esculetin. Biochim Biophys Acta 1982;713:68-72.View Abstract