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Horse Chestnut

Scientific Name(s): A. californica Nutt. (California buckeye)., A. glabra Willd. (Ohio buckeye)., A. turbinata Blume., Aesculus hippocastanum L. (horse chestnut).
Common Name(s): Aesculaforce, Buckeye, California buckeye, Castanea equine, Chestnut, Essaven, Horse chestnut, Japanese horse chestnut, Ohio buckeye, Semen hippocastani

Clinical Overview

Use

Oral horse chestnut seed extract is effective in the short-term treatment of mild to moderate long-term venous insufficiency, but not for post-thrombotic syndrome. Other investigations focus on the role of the major component aescin in male fertility, antiobesity, and anti-inflammatory effects. Aescin gel has been evaluated for use in bruising.

Dosing

Aescin 20 to 120 mg taken orally has been used for venous insufficiency and is available in tablet form. Oral tinctures and topical gels containing aescin 2% are also available.

Contraindications

Renal or hepatic impairment may be relative contraindications to the use of aescin or horse chestnut derivatives.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

The most commonly cited adverse effects include nausea and stomach discomfort, which may be minimized by the use of film-coated tablets. Other mild and infrequent complaints include headache, dizziness, and pruritus. Rare cases of allergy and anaphylaxis have been reported. A single case of acute effusive pericarditis that led to cardiac tamponade has been reported.

Toxicology

All parts of plants in the Aesculus family are potentially toxic, especially the seeds (nuts). Horse chestnut has been classified by the Food and Drug Administration (FDA) as an unsafe herb.

Botany

Members of the genus Aesculus grow as trees and shrubs, often attaining heights of 23 m. The fruit is a capsule with a thick, leathery husk that contains 1 to 6 dark seeds (nuts). As the husk dries, the nuts are released. The pink and white flowers of the plant grow in clusters. The tree is native to the woods of the Balkan region of southeastern Europe and to western Asia, but is now cultivated worldwide. The dried ripe seeds of the plant are of most medicinal interest.Chevallier 1996, USDA 2010, WHO 2004

History

Because of their prevalence, chestnuts have been used in traditional medicine and in a variety of commercial applications for centuries. Extracts of the bark have been used as a yellow dye, and the wood has been used for furniture and packing cases. In the western United States, the crushed, unripe seeds of the California buckeye were scattered into streams to stupefy fish, and leaves were steeped as tea to remedy congestion. The horse chestnut has been used as a traditional remedy for arthritis and rheumatism, as well as for gynecological bleeding and as a tonic.

Even though the seeds are toxic, several traditional methods were employed to rid them of their toxicity. Seeds were buried in swampy, cold ground during the winter to free them of toxic, bitter components, and then eaten in the spring after boiling. American Indians roasted the poisonous nuts, peeled and mashed them, and then leached the meal in lime water for several days, creating a meal used to make bread.Duke 1985, Evans 1989, Tyler 1988, WHO 2004

Chemistry

The seeds of Aesculus contain a variety of complex constituents. The seed oil contains 65% to 70% oleic acid. The seeds contain protein, ash, and 74% carbohydrate, and triterpene oligoglycosides from horse chestnut seeds have been isolated.

The main active constituents isolated from horse chestnut are aescin (10%) and prosapogenin. Aescin (escin) is a mix of the triterpene saponins alpha- and beta-aescin and cryptoaescin.

Bioflavonoids present include quercetin and kaepferol, and their derivatives. Antioxidants, such as proanthocyanidin, and coumarins, including the toxic esculin, as well as fraxin and pavietin, are also found in the Aesculus genus.

Specific assays have been described to quantify the aescin content of preparations, including high-pressure liquid chromatography, thin-layer chromatography, and mass spectroscopy.Curir 2007, Kapusta 2007, Ogawa 2008, Sirtori 2001, WHO 2004

Uses and Pharmacology

Anti-inflammatory

Animal data

Inhibition of cyclooxygenase activity of Japanese horse chestnut seed extract has been demonstrated in animal experiments.Guillaume 1994, Sato 2006, Sato 2007 The bark of Aesculus is also reported to possess the anti-inflammatory steroids stigmasterol, alpha-spinasterol, and beta-sitosterol.Senatore 1989, Tsutsumi 1967

Clinical data

Research reveals no clinical data regarding anti-inflammatory applications for horse chestnut extracts.

Cancer

Animal data

Beta-aescin has been evaluated in a number of in vitro studies and animal experiments for antiproliferative, apoptotic, and growth-inhibiting activities.Niu 2008, Patlolla 2006, Wang 2008 Reductions in the number of aberrant crypt foci, as well as deceased tumor growth, has been demonstrated in rats with induced colon cancer.Patlolla 2006, Wang 2008 The presence of an acyl group on other chemical constituents of horse chestnut seed extract may be important.Zhang 2007 Antioxidant and antimutagenic effects have also been described.Sato 2005 However, an article from one of these research groups has been withdrawn.Sato 2008

Clinical data

Research reveals no clinical data regarding chemotherapeutic applications for horse chestnut extracts.

Circulation

Animal data

In vitro and animal studies, as well as leg elevation studies, have demonstrated the antiedematous and venotonic effect of the extract. Suggested mechanisms of action include inhibition of the enzymes elastase and hyaluronidase, prevention of leukocyte activation, and influence on capillary filtration.Pittler 2012, Sirtori 2001, WHO 2004, Wollina 2006

Clinical data

Venous insufficiency

Meta-analyses and systematic reviews have consistently concluded that oral horse chestnut seed extract is safe and effective for the short-term treatment (up to 16 weeks) of mild to moderate long-term venous insufficiency.Pastor-Villaescusa 2015, Pittler 2012, Sirtori 2001, Vogel 2005, Underland 2012 Leg pain was significantly reduced (P < 0.05) in 6 of 7 trials (N = 543) for the extract versus placebo, and in the seventh trial improvement versus baseline was reported.Pittler 2012 Six trials (n = 502) suggested improved edema in favour of horse chestnut seed extract compared with placebo; whilst one study found the extract to be as effective as treatment with compression stockings.Pittler 2012

Post-thrombotic syndrome

A Cochrane review found 3 studies (up to 2015) of sufficient quality to conduct a meta-analysis on the effect of horse chestnut rutosides for treatment of post-thrombotic syndrome. No statistical significance in the rutoside treated group versus placebo or no treatment, and in comparison with compression stockings was found.Morling 2015 No studies were found in another Cochrane review for horse chestnut rutosides in the prevention of this syndrome.Morling 2015

Other circulation effects

Horse chestnut seed extract has been shown to be effective in reducing symptoms in hemorrhoids (bleeding and swelling), bruising (pain and swelling), and postoperative edema in limited clinical trials.Reynolds 2006, Sirtori 2001, WHO 2004 Beta-aescin may have a potential antiedematous role in the management of Bell palsy; however, clinical studies are lacking.Liu 2008

Fertility

Animal data

Varicocele-associated infertility may on part be due to testicular oxidative stress. Animal data suggest escin to demonstrate activity in venous malfunction.Fang 2010

Clinical data

A clinical study (n=219) evaluated the effect of 60mg escin daily over 2 months on varicocele-associated infertility. The researchers reported a significant improvement in sperm density, but not motility, compared with surgical intervention and a control group (Vitamin E, pentoxifylline and clomiphene).Fang 2010

Obesity

Animal data

Seed extract of Japanese horse chestnut has been evaluated by a limited number of researchers for antiobesity effects. Inhibition of pancreatic lipase in vitro has been demonstrated, leading to suggestions of an antiobesity mechanism of delayed intestinal absorption of dietary fat. Studies have shown the extract to prevent weight gain in high-fat diet mice, as well as decreased adipose tissue content and plasma triglycerol.Hu 2008, Kimura 2006, Kimura 2008 In one of the animal experiments, blood glucose was reduced following a single dose of extract.Kimura 2006

Clinical data

Research reveals no clinical data regarding antiobesity effects of horse chestnut extracts.

Dosing

Horse chestnut extracts typically are standardized on content of triterpene glycosides, calculated as the major component aescin.

Oral doses of standardized powdered extract 250 to 312.5 mg (equivalent to aescin 100 mg) twice a day have been cited in the Complete German Commission E Monographs.WHO 2004

Aescin 20 and 50 mg tablets are available. Doses of aescin 20 to 120 mg taken orally have been used for venous insufficiency.Pittler 2012, Suter 2006

Duration of use for the seed extract in clinical trials has been from 2 to 16 weeks, with steady state being attained after 8 twice-daily dosing intervals.Bassler 2003, Dickson 2004, Fang 2010, Pittler 2012

Intravenous aescin (5 to 10 mg) has been used in trials of postoperative edema.Sirtori 2001 Oral tinctures and topical gels containing aescin 2% are also available.Suter 2006, WHO 2004

Pregnancy / Lactation

Horse chestnut seed extract has been used in clinical trials including pregnant women with no apparent ill effects; however, in the absence of specific safety data, use in pregnancy or lactation is not recommended.WHO 2004

Interactions

Because case reports of toxic nephropathy with high-dose aescin exist, horse chestnut extracts should not be coadministered with other nephrotoxic drugs such as gentamicin.WHO 2004

The coumarin derivatives found in horse chestnut extracts may potentiate warfarin, as well as interfere with highly plasma-bound drugs.Heck 2000, Scott 2002, Vogel 2005

The possibility of interference with CYP34A metabolism and P-glycoprotein transport mechanisms of other drugs exists.Hellum 2008

Adverse Reactions

Renal or hepatic impairment may be relative contraindications to the use of aescin or horse chestnut derivatives.Vogel 2005 The issue of renal toxicity is uncertain. Trials conducted in the 1970s suggest aescin from whole horse chestnut extract is not toxic to the renal system; however, caution is still recommended.Sirtori 2001

The most commonly cited adverse effects include nausea and stomach discomfort, which may be minimized by the use of film-coated tablets.Dickson 2004, Leach 2006, Pittler 2012, WHO 2004 Other mild and infrequent complaints include headache, dizziness, and pruritus, although adverse dermatological reactions are rarely reported.Calapai 2014, Pittler 2012, Sirtori 2001 Rare cases of allergy and anaphylaxis have been reported.WHO 2004, Sirtori 2001 Consumption of 3 boxes of horse chestnut paste over 1.5 months was suspected as the cause of acute effusive pericarditis that resulted in cardiac tamponade in a 32-year-old previously healthy male.Edem 2016

Because hypoglycemic effects have been reported, asecin preparations should be used with caution in persons with diabetes.Kimura 2006, Vogel 2005, Yoshikawa 1996

Toxicology

Because Aesculus (horse chestnut) is classified by the FDA as an unsafe herb, all members of this genus should be considered potentially toxic.Duke 1985

Toxic properties have been attributed to a number of components, including glycosides and saponins. Potential toxins identified in the genus include nicotine, quercitin, quercitrin, rutin, saponin, and shikimic acid. The most important toxic principle is esculin. The nut is the most toxic part of the plant. Poisoning is characterized by muscle twitching, weakness, lack of coordination, pupil dilation, vomiting, diarrhea, depression, paralysis, and stupor. Children have been poisoned by drinking tea made from the leaves and twigs, and by eating the seeds; deaths have been reported following such ingestion. Amounts as little as 1% of a child's weight may be poisonous. Gastric lavage and symptomatic treatment have been suggested.Duke 1985, Hardin1974

A 30% ethanol extract of the seed was not mutagenic in the Salmonella test, and a 40% extract was not teratogenic or embryotoxic in rats or rabbits. Decreased birth weight has been observed in rabbits, while sodium aescinate had no effect on the fertility of male rats.WHO 2004 High lead levels are found in horse chestnut plants of Brazilian origin.Caldas 2004

References

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