Herb-Drug Interactions: Horse chestnut

Aesculus hippocastanum L. (Hippocastanaceae)

Synonym(s) and related species

Aesculus. Hippocastanum vulgare Gaertn.

Pharmacopoeias

Horse Chestnut (US Ph 32); Powdered Horse Chestnut (US Ph 32); Powdered Horse Chestnut Extract (The United States Ph 32).

Constituents

Horse chestnut seeds contain more than 30 saponins, a complex mixture known as ‘aescin’ or ‘escin’ (to which it may be standardised), based on the aglycones protoescigenin and barringtogenol-C. Other compounds including sterols and triterpenes, such as friedelin, taraxerol and spinasterol, and flavonoids, based on quercetin and kaempferol, are also present. The natural coumarins found in horse chestnut (such as aesculin (esculin) and fraxin) do not possess the minimum structural requirements for anticoagulant activity.

Use and indications

Horse chestnut extracts (aescin) are used to treat vascular insufficiency, especially varicose veins, venous ulcers, haemorrhoids and inflammation. They are usually applied as topical preparations, particularly gel formulations, but a licensed oral dosage form is also available. There is a considerable body of clinical and pharmacological evidence to support their use.

Pharmacokinetics

An isolated in vitro study suggests that horse chestnut may inhibit P-glycoprotein-mediated transport, assessed using digoxin as a substrate. In this study, horse chestnut did not inhibit cytochrome P450 isoenzyme CYP3A4.Similarly, in a previous study, the authors briefly noted that, in vitro, horse chestnut had little inhibitory effect on CYP1A2, CYP2D6 and CYP3A4.3 For information on the pharmacokinetics of individual flavonoids present in horse chestnut, see under flavonoids.

Interactions overview

One in vitro study suggests that horse chestnut may affect P-glycoprotein, and could therefore affect the pharmacokinetics of drugs such as digoxin, although the clinical significance of this is unknown. Some have suggested that horse chestnut may interact with anticoagulants, presumably based on its natural coumarin content, but the coumarins present are not known to possess the structural requirements necessary for anticoagulant activity. For more information, see Natural coumarins + Warfarin and related drugs. For information on the interactions of individual flavonoids present in horse chestnut, see under flavonoids.

Horse chestnut + Digoxin

The interaction between horse chestnut and digoxin is based on experimental evidence only.

Evidence, mechanism, importance and management

An in vitro study to investigate the effects of a horse chestnut product (Venostat) on P-glycoprotein transport found that the extract inhibited the transport of digoxin by P-glycoprotein to a minor extent. Nevertheless, the authors predicted that inhibitory levels might easily be reached in the small intestine with usual therapeutic doses of horse chestnut.

Since this appears to be the only available study, this inhibition of digoxin transport needs confirming, and then an in vivo clinical study would be required to assess whether horse chestnut does alter digoxin absorption on concurrent use, and whether any changes are clinically relevant. No specific recommendations can be made on the basis of this single in vitro study.

Horse chestnut + Food

No relevant interactions found.

Horse chestnut + Herbal medicines

No interactions found.