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Aesculus hippocastanum
Semen Hippocastani


Aesculus castanea Gilib., A. procera Salisb., Castanea equina, Hippocastanum vulgare Gaertner. Not to be confused with the common chestnut, Castanea dentata (Marshall) Burkh. (Fagaceae) or related Castanea species
General appearance
Globulous or ovoid, 2–4 cm in diameter. The 2 large cotyledons fleshy, oily and starchy, often connate with a line of suture more or less visible; covered by a shiny dark-brown tegument with a large whitish spot corresponding to the hilum; tegument creamy white in the immature seed, takes on a brown tinge during maturation, becoming dark brown when mature. Curved radicle occupies a depression either on the commissure of the cotyledons or on the dorsal side of 1 of the cotyledons.

Major chemical constituents

The major constituents are triterpene saponins (up to 10%), collectively referred to as aescin (also known as escin), and are considered the active therapeutic principles. Aescin exists in three forms, a-aescin, b-aescin and cryptoaescin, which are differentiated by their physical properties. b-aescin is a mixture of more than 30 different glycosides derived from the triterpene aglycones protoaescigenin (also known as protoescigenin) and barringtogenol C. Other constituents include flavonoids.

Medicinal uses of Aesculus hippocastanum

Uses supported by clinical data
Aesculus hippocastanum: Internally, for treatment of symptoms of chronic venous insufficiency, including pain, feeling of heaviness in the legs, nocturnal calf-muscle spasms, itching and oedema. Externally, for the symptomatic treatment of chronic venous insufficiency, sprains and bruises.

Uses described in pharmacopoeias and in traditional systems of medicine
Treatment of coronary heart disease.

Uses described in folk medicine, not supported by experimental or clinical data
Treatment of bacillary dysentery and fevers. Also as a haemostat for excessive menstrual or other gynaecological bleeding, and as a tonic.


Experimental pharmacology

Anti-inflammatory activity

Intravenous administration of a 95% ethanol extract of Semen Hippocastani (0.2–0.4 ml/kg body weight) decreased histamine-induced erythema in guineapigs. Intragastric administration of a 30% ethanol extract of the seeds suppressed carrageenan-induced footpad oedema and adjuvant-induced arthritis in rats (at doses of 0.6 and 1.5 ml/kg body weight, respectively). Intraperitoneal administration of a saponin fraction isolated from a seed extract exhibited analgesic, anti-inflammatory and antipyretic activities in vivo; the saponin fraction also inhibited prostaglandin synthetase activity in vitro. Intragastric administration of a hydroalcoholic extract of the seeds to rats (200– 400mg/kg body weight) suppressed footpad oedema induced by peroxide and carrageenan.
Intravenous or oral administration of aescin to rats (0.5–120mg/kg body weight) inhibited footpad oedema induced by dextran, and granuloma induced by cotton pellet and formalin paper.
Intravenous administration of aescin to rats reduced footpad oedema induced by ovalbumin, formalin and dextran.

Vasoactive effects

A hydroalcoholic extract of the seeds induced contractions in canine saphenous veins in vitro, and an intravenous bolus (25–50 mg) increased venous pressure in perfused canine saphenous veins in vivo.
Cutaneous capillary hyperpermeability induced by chloroform, serotonin and histamine also decreased in rats and rabbits after intragastric administration of a hydroalcoholic extract of the seeds (50–400mg/kg body weight). Aescin (5–10mg/ml) increased the tension of isolated human saphenous veins and rabbit portal veins in vitro. The effect was due to preferential formation of prostaglandin F2a and was reversed by treatment with indometacin.
The vasoactive effects of aescin were investigated in isolated peripheral blood vessels, isolated arteries and veins (constant-flow perfused cat rear paw, isolated perfused carotid artery of the guinea-pig and iliac veins of the pig). Aescin had a biphasic effect on blood vessels: initial transient dilation was followed by increased tone, which was long lasting in isolated arteries and veins, but was transient in isolated peripheral blood vessels. Aescin has also been shown to inhibit hyaluronidase activity in vitro (IC50 149.9mmol/l). A hydroalcoholic extract of the seeds (250mg/ml) reduced lipid peroxidation and had radical-scavenging properties (IC50 0.24mg/ml for superoxide dismutase radicals).

Clinical pharmacology

Chronic venous insufficiency and related conditions

Nine placebo-controlled clinical trials (eight double-blind, one single-blind, seven with crossover design) assessed the efficacy of oral administration of a standardized Semen Hippocastani extract (250–600 mg, equivalent to 100– 150mg aescin daily) in a sustained-release form for the symptomatic treatment of patients with chronic venous insufficiency (CVI). In one study, 96 patients with CVI received the extract over two treatment periods of 20 days each. Symptomatic improvement in skin colour, venous prominence, oedema, dermatosis, and pain, itching and feeling of heaviness in the legs were observed in the treated patients. However, the methodology of this study was poor, and no statistical analysis was performed. Two later studies assessed the efficacy of the extract in 212 patients and 95 patients with CVI, using a numerical scale to rate the severity of symptoms. A significant symptomatic improvement (P < 0.01–0.05) in oedema, calf-muscle spasms, pain and feeling of heaviness in the legs was observed in patients treated with the extract (during two treatment periods of 20 days each). The efficacy of the extract was assessed in a double-blind study of 20 female patients (13 with pregnancy-related varicose veins and seven with CVI) during two treatment periods of 14 days each. A significant reduction in leg volume (114ml in patients with varicose veins and 126 ml in patients with CVI, P < 0.01) was demonstrated by water plethysmography in patients treated with the extract. Another double-blind study assessed the efficacy of the extract in the treatment of 74 patients with CVI and lower-leg oedema. In patients treated with the extract, the leg volume following induction of oedema was reduced from 32ml to 27 ml (determined by water plethysmography); in the placebo group the leg volume increased from 27 ml to 31 ml. Two further studies investigated the effects of the extract on the intravascular volume of the lower-extremity veins and on interstitial filtration (measured indirectly by venous-occlusion or water plethysmography) in patients with CVI. In one of the studies, after a single dose of 600 mg extract (equivalent to 100 mg aescin), the transcapillary filtration coefficient decreased by 22%, as compared with a slight increase in the coefficient of the placebo group. This study demonstrated that the extract exerted its action primarily by  reducing capillary permeability. In the other study, patients treated daily with 600 mg extract (equivalent to 100 mg aescin) for 28 days showed a significant reduction in extravascular volume of the foot and ankle (P < 0.01), as well as a significant improvement in oedema, and feelings of tension, pain, fatigue and itching of the legs (P < 0.05). However, no changes in venous capacity or calf-muscle spasms were observed.
The efficacy of the extract was assessed in a randomized, parallel, doubleblind study of 40 patients with venous oedema due to chronic deep-vein incompetence stage II. Patients received 369–412 mg extract (equivalent to 75mg aescin) twice daily for 6 weeks. A significant reduction was observed in leg volume (measured by water plethysmography after oedema induction) and leg circumference in the treated group (P < 0.01). A randomized, singleblind, parallel study compared the efficacy and safety of class II compression stockings with the extract or placebo in 240 patients with CVI. Patients in the treatment group received 300 mg extract (equivalent to 50mg aescin) twice daily for 12 weeks. The lower-leg volume of the affected limbs decreased by an average of 43.8 ml in patients treated with the extract and by 46.7 ml in patients wearing compression stockings. In the placebo group, the lower-leg volume increased by 9.8 ml. Thus, treatment with the extract or wearing class II compression stockings resulted in similar decreases in lower-leg volume.
A randomized, double-blind trial compared the efficacy of a standardized extract (360–412 mg, equivalent to 75 mg aescin, twice daily) and oxerutins (1000mg O-(b-hydroxyethyl)-rutinosides twice daily) in 40 patients with CVI and  peripheral venous oedema. A reduction in oedema (based on measurement of leg circumference) was observed in both treatment groups. Another randomized, double-blind study compared the efficacy of a standardized seed extract with oxerutins in the treatment of 137 postmenopausal women with chronic deep-vein incompetence stage II. Following a 1-week placebo run-in, patients were treated daily with either 600 mg extract (equivalent to 100mg aescin) or 1000 mg oxerutins for 12 weeks, or 100 mg oxerutins for 4 weeks followed by 500 mg oxerutins for 12 weeks. Patients were observed for 6 weeks after treatment; the group treated with 1000 mg oxerutins had the greatest decrease in leg volume.
A placebo-controlled, double-blind crossover study assessed the effect of a standardized seed extract in the symptomatic treatment of 52 pregnant women with venous insufficiency. Patients were treated with either one capsule containing 300 mg extract (equivalent to 50 mg aescin) or a placebo twice daily for 2 weeks. The extract was superior to the placebo in reducing oedema and symptoms such as leg pain, fatigue and itching. Patients treated with the extract also showed a greater resistance to oedema induction. The ability of a standardized seed extract to reduce oedema was investigated in a randomized, double-blind, placebo-controlled trial of 30 patients with CVI.
A significant reduction in leg circumference was found in the treatment group (P < 0.05) as compared to the placebo group (P < 0.05). A double-blind placebo-controlled study investigated the effect of a standardized seed extract (one dose of 600 mg, equivalent to 100mg aescin) on vascular capacity and filtration in the arms and legs of 12 healthy volunteers. Using vein plethysmography, the study showed a decrease in both vascular capacity and filtration coefficient in subjects treated with the extract. The effect of a standardized seed extract (one dose of 1800mg) on the flow velocity of venous blood between the instep and the groin was quantitatively determined in 30 patients with varicose veins by the xenon-133 appearance method. Blood flow increased by >30%, with a lasting effect observed after 12 days of treatment. Blood viscosity was also reduced and there was a 73% improvement in subjective complaints. A randomized double-blind study assessed the effect of a standardized seed extract on lower-leg oedema in 10 healthy volunteers during a 15-hour airflight. A single dose of the extract (600 mg, equivalent
to 100 mg aescin) completely prevented or significantly reduced the increase in ankle and foot oedema (P < 0.05), determined by measuring the circumference of the ankle and heel before and after flying. A postmarketing surveillance study of over 5000 patients suffering from CVI demonstrated that treatment with a standardized seed extract (equivalent to 75mg aescin) twice daily for 4–10 weeks reduced the symptoms of leg pain, fatigue, oedema and itching. In a multicentre study without controls, 71 patients with CVI were treated daily with a topical gel containing 2% aescin. After 6 weeks of treatment, a significant reduction in ankle oedema (reduction of 0.7 cm in the ankle circumference, P < 0.001) and a significant reduction in the symptom score (60%, P < 0.001) was reported. In a postmarketing surveillance study involving over 4000 patients with CVI, treatment with a standardized extract of the crude drug (equivalent to 50 mg aescin) twice daily improved typical symptoms in more than 85% of patients. A criteria-based systematic review assessed the randomized, double-blind, placebo-controlled trials of standardized seed extracts for symptomatic treatment of CVI. The data were extracted from the trials in a standardized manner, and the methodological quality and outcome of each trial were assessed by two independent reviewers. In all trials, the extract was shown to be superior to the placebo. Use of the extract was associated with a decrease in lower-leg oedema, and a reduction in the circumference of the calf and ankle. Other symptoms such as leg pain, itching and fatigue were reduced. Results from five comparative trials demonstrated that the extract was as effective as oxerutins, and one of the five trials showed that the extract was as effective as compression therapy.


Semen Hippocastani is contraindicated in cases of known allergy to plants of the Hippocastanaceae family.


No information available.

News and Journals

1. Pharmacopée française. Paris, Adrapharm, 1996.
2. Deutsches Arzneibuch. Stuttgart, Deutscher Apotheker Verlag, 1998.
3. Blaschek W et al., eds. Hagers Handbuch der pharmazeutischen Praxis. Folgeband 2:
Drogen A–K, 5th ed. Berlin, Springer-Verlag, 1998.
4. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, PA, Blakiston, 1950.
5. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.
6. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at
Chicago, IL, February 9, 1998 production (an online database available directly
through the University of Illinois at Chicago or through the Scientific and Technical
Network [STN] of Chemical Abstracts Services).
7. Bombardelli E, Morazzoni P. Aesculus hippocastanum L. Fitoterapia, 1996, 67:483–510.
8. Quality control methods for medicinal plant materials. Geneva, World Health Organization,
9. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1996.
10. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World
Health Organization, 1997 (document WHO/FSF/FOS/97.7).
11. Kockar OM et al. Quantitative determination of escin. A comparative study of HPLC
and TLC-densitometry. Fitoterapia, 1994, 65:439–443.
12. Vanhaelen M, Vanhaelen-Fastre R. Quantitative determination of biologically active
constituents in medicinal plant crude extracts by thin-layer chromatography–
densitometry. Journal of Chromatography, 1983, 281:263–271.
13. Alter H. Zur medikamentösen Therapie der Varikosis. Zeitschrift für Allgemeine
Medizin, 1973, 49:1301–1304.
14. Bisler H et al. Wirkung von Rosskastaniensamenextrakt auf die transkapilläre Filtration
bei chronischer venöser Insuffizienz. Deutsche Medizinische Wochenschrift,
1986, 111:1321–1328.
15. Diehm C et al. Medical edema protection—clinical benefit in patients with chronic
deep vein incompetence. A placebo-controlled double-blind study. Vasa, 1992, 21:
16. Diehm C et al. Comparison of leg compression stocking and oral horse-chestnut
seed extract therapy in patients with chronic venous insufficiency. Lancet, 1996, 347:
17. Friederich HC et al. Ein Beitrag zur Bewertung von intern wirksamen Venenpharmaka.
Zeitschrift für Hautkrankheiten, 1978, 53:369–374.
18. Lohr E et al. Ödemprotektive Therapie bei chronischer Veneninsuffizienz mit
Ödemneigung. Münchener Medizinische Wochenschrift, 1986, 128:579–581.
19. Neiss A, Böhm C. Zum Wirksamkeitsnachweis von Rosskastaniensamenextrakt
beim varikösen Symptomenkomplex. Münchener Medizinische Wochenschrift, 1976:
20. Rudofsky G et al. Ödemprotektive Wirkung und klinische Wirksamkeit von Rosskastaniensamenextrakt
im Doppelblindversuch. Phlebologie und Proktologie, 1986, 15:
21. Steiner M, Hillemanns HG. Untersuchung zur ödemprotektiven Wirkung eines
Venentherapeutikums. Münchener Medizinische Wochenschrift, 1986, 31:551–552.
22. Götz AK, Giannetti BM. Naturstoffe in der Therapie stumpfer
Sportverletzungen—heute noch zeitgemäss? Erfahrungsheilkunde, 1990, 6:362–
23. Calabrese C, Preston P. Äscin bei der Behandlung von Hämatomen—eine randomisierte
doppelblind-Studie. Zeitschrift für Phytotherapie, 1994, 60:112.
24. Geissbühler S, Degenring FH. Behandlung von chronisch venöser Insuffizienz mit
Aesculaforce Venengel. Schweizerische Zeitschrift für Ganzheits Medizin, 1999, 11:
WHO monographs on selected medicinal plants
25. Materia medica of Chinese herbology. Shanghai, State Administration of Traditional
Chinese Medicine, Shanghai Scientific and Technical Press, 1996.
26. Arnold M, Przerwa M. Die therapeutische Beeinflussbarkeit experimentell erzeugter
Ödeme. Arzneimittel-Forschung, 1976, 26:402–409.
27. Leslie GB. A pharmacometric evaluation of nine Bio-Strath herbal remedies. Medita,
1978, 8:3–19.
28. Cebo B et al. Pharmacological properties of saponin fractions obtained from domestic
crude drugs: Saponaria officinalis, Primula officinalis and Aesculus hippocastanum.
Herba Polonica, 1976, 22:154–162.
29. Guillaume M, Padioleau F. Veinotonic effect, vascular protection, anti-inflammatory
and free-radical scavenging properties of horse chestnut extract. Arzneimittel-
Forschung, 1994, 44:25–35.
30. Aizawa Y et al. Anti-inflammatory action of aescin. Intravenous injection. Oyo
Yakuri, 1974, 8:211–213.
31. Damas P et al. Anti-inflammatory activity of escin. Bulletin de la Société royale des Sciences
de Liège, 1976, 45:436–440.
32. Tarayre JP et al. Pharmacological study of some capillary-acting substances. Annales
de Pharmacie française, 1975, 33:467–469.
33. Girerd RJ et al. Archives for International Pharmacodynamics, 1961, 133:127–130.
34. Preziosi P, Manca P. The anti-edematous and anti-inflammatory effects of aescin and
its relation to the hypophyseal–adrenal system. Arzneimittel-Forschung, 1965, 15:404–
35. Longiave D et al. The mode of action of aescin on isolated veins: relationship with
PGF2a. Pharmacological Research Communications, 1978, 10:145–152.
36. Felix W et al. Vasoaktive Wirkungen von alpha-Aescin. Ergebnisse der Angiologie, 1984,
37. Facino RM et al. 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. Archiv der Pharmazie
(Weinheim), 1995, 328:720–724.
38. Masaki H et al. Active-oxygen scavenging activity of plant extracts. Biological and
Pharmaceutical Bulletin, 1995, 18:162–166.
39. Erler M. Rosskastaniensamenextrakt bei der Therapie peripherer venöser Ödeme.
Die Medizinische Welt, 1991, 42:593–596.
40. Rehn D et al. Comparative clinical efficacy and tolerability of oxerutins and horse
chestnut extract in patients with chronic venous insufficiency. Arzneimittel-Forschung,
1996, 46:483–487.
41. Steiner M, Hillemanns HG. Venostatin retard in the management of venous problems
during pregnancy. Phlebology, 1990, 5:41–44.
42. Pilz E. Ödeme bei Venenerkrankungen. Die Medizinische Welt, 1990, 41:1143–1144.
43. Pauschinger P. Neuere Untersuchungen zur Wirkung von Venostasin retard auf die
kapilläre Funktion. Ergebnisse der Angiologie, 1984, 30:129–137.
44. Klemm J. Strömungsgeschwindigkeit von Blut in varikösen Venen der unteren
Extremitäten. Münchener Medizinische Wochenschrift, 1982, 124:579–582.
45. Marshall M, Dormandy JA. Oedema of long-distance flights. Phlebology, 1987, 2:
46. Greeske K, Pohlmann BK. Rosskastaniensamenextrakt—ein wirksames Therapieprinzip
in der Praxis. Fortschritte der Medizin, 1996, 114:196–200.
47. Masuhr T et al. Nutzen-Risiko-Bewertung von Venoplant® retard, einem auf Aescin
standardisierten Präparat aus Rosskastaniensamenextrakt, bei Patienten mit chronischer
Veneninsuffizienz. Top Medizin, 1994, 8:21–24.
48. Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency.
A criteria-based systematic review. Archives of Dermatology, 1998, 134:1356–
Semen Hippocastani
49. Calabrese C, Preston P. Report on the results of a double-blind, randomized, singledose
trial of a topical 2% aescin gel versus placebo in the acute treatment of experimentally
induced hematoma in volunteers. Planta Medica, 1993, 59:394–397.
50. Grasso A, Corvaglia E. Due casi di sospetta tubulonefrosi tossica da escina. Gazzetta
Medica Italiana, 1976, 135:581–584.
51. Schimmer O et al. An evaluation of 55 commercial plant extracts in the Ames mutagenicity
test. Pharmazie, 1994, 49:448–451.
52. Kreybig H, Prechtel K. Toxizitäts- und Fertilitätsstudien mit Aescin bei der Ratte.
Arzneimittel-Forschung, 1977, 7:1465–1466.
53. Leslie GB, Salmon G. Repeated dose toxicity studies and reproductive studies on
nine Bio-Strath herbal remedies. Swiss Medicine, 1979, 1:1–3.
54. Liehn HD et al. A toxicological study of extractum Hippocastani seed (EHS). Panminerva
Medicine, 1972, 14:84–91.
55. Blumenthal M et al., eds. The complete German Commission E monographs. Austin, TX,
American Botanical Council, 1998.
56. Escribano MM et al. Contact urticaria due to aescin. Contact Dermatitis, 1997,