The thick twigs of these medium-sized trees have glistening buds in spring and bear opposite leaves composed of five leaflets in a finger-like arrangement. The yellowish flowers rise in large, upright, dense, candle-like clusters at branch ends during June. The prickly fruit contains 1 to 3 nutlike seeds, glossy and leathery brown with a pale scar on each that gives the tree its name. These trees commonly grow in rich, moist woods or along river banks and are often planted as ornamentals.
Aesculus hippocastanum L. (Hippocastanaceae).
Synonyms and Part Used
Aesculetin, fraxin (fraxetin glucoside), scopolin (scopoletin glucoside).
Flavonol (kaempferol, quercetin) glycosides including astragalin, isoquercetrin, rutin; leucocyanidin (quercetin derivative).
French pharmacopoeial standard, not less than 3% aescin. A mixture of saponins collectively referred to as ‘aescin’ (3–10%); α- and β-escin as major glycosides.
Type unspecified but likely to be condensed in view of the epicatechin content (formed during hydrolysis of condensed tannins).
Allantoin, amino acids (adenine, adenosine, guanine), choline, citric acid, phytosterol.
Horse–chestnut is not used in foods.
Traditionally, horse–chestnut has been used for the treatment of varicose veins, haemorrhoids, phlebitis, diarrhoea, fever and enlargement of the prostate gland. It can be used for treatment of chronic venous insufficiency in the legs.
0.2–1.0 g three times daily.
Extracts equivalent to 50–150 mg triterpenes calculated as aescin.
Documented studies have concentrated on the actions of the saponins, in particular, aescin.
In vitro and animal studies
Anti–inflammatory and anti–oedema effects :
Anti–inflammatory activity in rats has been documented for both a fruit extract and the saponin fraction.Anti–inflammatory activity in the rat has been reported to be greater for a total horse–chestnut extract compared to aescin. In addition, an extract excluding aescin also exhibited activity, suggesting that horse–chestnut contains anti–inflammatory agents other than aescin. No difference in activity was noted when the horse–chestnut extracts were administered prior to and after dextran (inflammatory agent). It has been proposed that aescin affects the initial phase of inflammation by exerting a ‘sealing’ effect on capillaries and by reducing the number and/or diameter of capillary pores.
Effects on venous tone
Horse–chestnut extract (16% aescin, 0.2 mg/mL) and also aescin (0.1 mg/mL) induced contractions in isolated bovine and human veins. Concentration–dependent contractions of isolated canine veins were observed with a horse–chestnut extract (16% aescin, 5 × 10−4 mg/mL). A standardised extract (16% aescin, 50 mg, given intravenously) increased femoral venous pressure in anaesthetised dogs, and decreased cutaneous capillary hyperpermeability in rats (200 mg/kg, given orally).
In addition, the saponin fraction has been reported to exhibit analgesic and antigranulation activities in rats,to reduce capillary permeability, and to produce an initial hypotension followed by a longer lasting hypertension in anaesthetised animals. Prostaglandin production by venous tissue is thought to be involved in the regulation of vascular reactivity.Prostaglandins of the E series are known to cause relaxation of venous tissues whereas those of the Fα series produce contraction. Increased venous tone induced by aescin in vitro was found to be associated with an increased PGF2α synthesis in the venous tissue.
In vitro, aescin has been documented to inhibit hyaluronidase activity (IC50 150 μmol/L).
A saponin fraction of horse–chestnut has been reported to contract isolated rabbit ileum.
Antiviral activity in vitro against influenza virus (A2/Japan 305) has been described for aescin.
Metabolism studies of aescin in the rat have concluded that aescin toxicity is reduced by hepatic metabolism.
Flavonoids and tannins are generally recognised as having anti–inflammatory and astringent properties, respectively.
Chronic venous insufficiency
Several studies have assessed the effects of horse–chestnut seed extract in patients with chronic venous insufficiency, a common condition which causes oedema of the lower leg.
It was concluded that horse–chestnut seed extract is effective as a symptomatic, short–term treatment for chronic venous insufficiency, but that further well–designed clinical trials are required to confirm this.
Glycosaminoglycan hydrolyses are enzymes involved in the breakdown of substances (proteoglycans) that determine capillary rigidity and pore size (thus influencing the passage of macromolecules into the surrounding tissue). Proteoglycans also interact with collagen, stabilising the fibres and regulating their correct biosynthesis.The activity of these enzymes was found to be raised in patients with varicosis, compared with healthy patients.It was proposed that horse–chestnut may act at the site of enzyme release, exerting a stabilising effect on the lysosomal membrane.
The cosmetic applications of horse–chestnut have been reviewed; these effects are attributed to properties associated with the saponin constituents.
Two incidences of toxic nephropathy have been reported and were stated as probably secondary to the ingestion of high doses of aescin.In Japan, where horse–chestnut has been used as an anti–inflammatory drug after surgery or trauma, hepatic injury has been described in a male patient who received an intramuscular injection of a proprietary product containing horse–chestnut.Liver function tests showed a mild abnormality and a diagnosis of giant cell tumour of bone (grade 2) by bone biopsy was made. Other side–effects stated to have been reported for the product include shock, spasm, mild nausea, vomiting and urticaria.
The effect of aescin, both free and albumin–bound, on renal tubular transport processes has been studied in the isolated, artificially perfused frog kidney.Aescin was found to primarily affect tubular, rather than glomerular,epithelium and it was noted that binding to plasma protein (approximately 50%) protects against this nephrotoxicity. Aescin was thought to be neither secreted nor reabsorbed in the tubules, and the concentration of unbound aescin filtered through the kidney (13%) was considered to be too low to have toxic effects. The authors commented that the symptoms of acute renal failure in humans are caused primarily by interference with glomeruli and in view of this, the nephrotoxic potential of aescin is probably only relevant when the kidneys are already damaged and also if the aescin is displaced from its binding to plasma protein.
A proprietary product containing horse–chestnut (together with phenopyrazone and cardiac glycoside–containing plant extracts) has been associated with the development of a drug–induced auto–immune disease called ‘pseudolupus syndrome’ in Germany and Switzerland.(16,17) The individual component in the product responsible for the syndrome was not established.
It has been noted that death occurs rapidly in animals given large doses of aescin, due to massive haemolysis. Death is more prolonged in animals given smaller doses of aescin.
LD50 values for aescin have been estimated in mice, rats and guinea–pigs and range from 134 to 720 mg/kg (by mouth) and from 1.4 to 15.2 mg/kg (intravenous njection).The total saponin fraction has been reported to be less toxic in mice (intraperitoneal injection) compared to the isolated aescin mixture (LD50 46.5 mg/kg and 9.5 mg/kg,respectively).The haemolytic index of horse–chestnut is documented as being 6000, compared with 9500 to 12 500 for aescin.Daily doses in rats (100 mg/kg, orally) of a standardised extract of horse–chestnut (16% aescin) did not produce teratogenic effects, and the extract was negative in the Ames test with Salmonella typhimurium TA98 without actuation.
Horse–chestnut may be irritant to the gastrointestinal tract due to the saponin constituents. Saponins are generally recognised to possess haemolytic properties, but are not usually absorbed from the gastrointestinal tract following oral administration. Horse–chestnut may interfere with anticoagulant/coagulant therapy (coumarin constituents). Aescin, the main saponin component in horse–chestnut, binds to plasma protein and may affect the binding of other drugs. Horse–chestnut should be avoided by patients with existing renal or hepatic impairment.
Pregnancy and lactation
The safety of horse–chestnut during pregnancy and lactation has not been established. In view of the pharmacologically active constituents present in horse–chestnut, use during pregnancy and lactation is best avoided.
Horse–chestnut is traditionally characterised by its saponin components, in particular aescin which represents a mixture of compounds. However, horse–chestnut also contains other pharmacologically active constituents including coumarins and flavonoids. The traditional use of horse–chestnut in peripheral vascular disorders has largely been substantiated by studies in animals and humans, in which anti–inflammatory and capillary stabilising effects have been observed. There is evidence from randomised, double–blind, controlled clinical trials to support the use of horse–chestnut seed extract in the treatment of symptoms of chronic venous insufficiency. Many of the documented activities can probably be attributed to the saponin and flavonoid constituents in horse–chestnut.