Herbal Medicine: Expanded Commission E

Latin Name: Aesculus hippocastanum
Pharmacopeial Name: Hippocastani semen
Other Names: panish chestnut, buckeye

• Overview
• Description
• Chemistry and Pharmacology
• Uses
• Contraindications
• Side Effects
• Use During Pregnancy and Lactation
• Interactions with Other Drugs
• Dosage and Administration
• References
• Additional Resources

Overview

Horse chestnut seed extract (HCSE) is derived from a deciduous tree that grows up to 25 meters. It has spread throughout the northern hemisphere, but is native to the central Balkan peninsula. HCSE is relatively new on the United States botanical market. This phytomedicine is gaining in popularity due to the significant quantity of clinical evidence that documents its efficacy as a treatment for varicose veins, chronic venous insufficiency (CVI), and related vascular disorders.

In 1994, Commission E revised the previous horse chestnut monograph to include a detailed description of the pharmacokinetics (the absorption/resorption of substances in the human body) of the approved herb. The old monograph (December 5, 1984) on horse chestnut leaf and flower did not include these findings, and thus the herb was not approved. Also, the approved formulation for horse chestnut was more rigorously defined than earlier. The 1984 monograph defined the drug as horse chestnut seed with 3% triterpene glycosides calculated as escin (aescin), and indicated a daily dose corresponding to 30150 mg escin. The 1994 monograph pertains to a defined extract only with an escin content of 1621% in a slow-release dosage form.

Numerous studies have been performed on the defined extract. A clinical study of 22 patients with proven venous insufficiency measured by capillary filtration coefficient and intravascular volume of the lower legs showed that 1200 mg of HCSE, standardized to 50 mg escin per capsule, lowered capillary filtration by 22% in three hours (Bisler et al., 1986). In a randomized, placebo-controlled, parallel, double-blind study of 40 patients with venous edema in chronic deep vein incompetence, the edema-reducing effect of HCSE was deemed statistically significant. Measurements of leg circumference and other relevant indicators showed HCSE to be a safe and effective adjunct to compression therapy (Diehm et al., 1992). A study of 240 patients indicated that HCSE is effective as an adjunct therapy with compression stockings for the treatment of edema resulting from CVI (Diehm et al., 1996).

Other recent clinical studies have evaluated oral HCSE and topically applied gel for CVI. In a multi-center, placebo-controlled study on 60 patients (half receiving placebo), HCSE tablets (6390 mg extract, standardized to 20 mg escin) (Aesculaforce/Venaforce, Bioforce, Switzerland), given in a dosage of three tablets twice daily for six weeks, were effective in reducing edema in the ankles and the venous filling rate (Shah et al., 1997). A gel (Aesculuaforce/Venacorce Vein Gel, Bioforce) containing 2% escin was successful in a recent non-controlled multi-center trial for six weeks on 71 patients with CVI and edema (Geissb hler and Degenring, 1999). Ankle circumference was reduced by a statistically significant 0.7 cm and the sum of the symptoms score was reduced by approximately 60% as determined by physicians and patients. In both studies, the principal author was employed by the manufacturer.

An observational study of 800 German general practitioners treating over five thousand patients concluded that the symptoms (pain, tiredness, tension and swelling in the leg, itching, and tendency towards edema) all improved significantly or disappeared completely. The authors, employees of the leading manufacturer of HCSE (Venostatin retard, Klinge Pharma, Germany), concluded that compared to compression therapy, HCSE had the advantage of better compliance (Greeske and Pohlmann, 1996).

A recent systematic review of 13 clinical studies conducted on HCSE concluded that the superiority of the medication compared to placebo was established by the studies. HCSE was as effective as rutosides (the conventional treatment) in five studies. Adverse effects were mild and infrequent (Pittler and Ernst, 1998). In addition to studies published in 1999 on the external gel, at least 22 clinical studies of various designs have been conducted on HCSE on a total of 918 patients: 12 trials were double-blind, placebo-controlled, two were double-blind compared with a conventional drug, one was single-blind, placebo-controlled, two were open and placebo-controlled and five were open studies (Degenring, 1996; Shah et al., 1997). Clinical and pharmacological studies were evaluated in a recent literature review of HCSE (Bombardelli and Morazzoni, 1996).

German pharmacopeial grade horse chestnut seed, which is the material required for manufacture of the above specified native dry extract, consists of the dried seed of Aesculus hippocastanum L. It must contain not less than 3.0% triterpene glycosides, calculated as anhydrous escin, with reference to the dried drug. Botanical identity must be confirmed using thin-layer chromatography (TLC) as well as macroscopic and microscopic examinations (DAB, 1997). The typical drug-to-extract ratio for this native dry extract will fall within the range of 5.08.0:1 (w/w) depending on the chemical composition of the starting material and the subsequent yield of soluble extractive.

Description

A dry extract manufactured from horse chestnut seeds, A. hippocastanum L. [Fam. Hippocastanaceae], adjusted to a content of 1620% triterpene glycosides calculated as anhydrous escin.

Chemistry and Pharmacology

Horse chestnut seed contains 36% of a complex mixture of triterpene saponins collectively referred to as escin (Morgan and Bone, 1998), including the triterpene oligoglycosides escins, Ia, Ib, IIa, IIb, and IIIa (Yoshikawa et al., 1996), the acylated polyhydroxyoleanene triterpene oligoglycosides escins IIIb, IV, V, and VI and isoescins Ia, Ib, and V (Yoshikawa et al., 1998), and the sapogenols hippocaesculin and barringtogenol-C (Konoshima and Lee, 1986); flavonoids (e.g., flavonol glycosides); condensed tannins (Newall et al., 1996); quinones; sterols, including stigmasterol, a-spinasterol, and b-sitosterol; and fatty acids, such as linolenic, palmitic, and stearic acids (Leung and Foster, 1996).

As found in different animal experiments, the principal ingredient in HCSE is the triterpene glycoside mixture, aescin (escin), which has an anti-exudative and vascular-tightening effect. There are indications that HCSE reduces the activity of lysosomal enzymes that is increased in chronic pathological conditions of the veins, so that the breakdown of glycoacalyx (mucopolysaccharides) in the region of the capillary walls is inhibited. The filtration of low-molecular proteins, electrolytes, and water into the interstitium is inhibited through a reduction of vascular permeability. Using placebo as reference, a significant reduction of transcapillary filtration has been demonstrated in pharmacological studies involving human subjects, and a significant improvement shown in the symptoms of chronic venous insufficiency (sensation of tiredness, heaviness and tension, pruritus, pain and swelling in the legs) in randomized double-blind studies and cross-over studies.

Pilot studies are available on the toxicology of HCSE. The oral LD50 of the extract is 990 mg per kg body weight in mice, 2,150 mg per kg body weight in rats, 1,530 mg per kg body weight in rabbits, and 130 mg per kg body weight in dogs. In rats, the 'no effect' dose is between 9 and 30 mg per kg body weight after intravenous administration of HCSE over a period of eight weeks. Chronic administration above 80 mg per kg body weight over a period of 34 weeks produced gastric irritation in dogs. In rats, no toxic changes were observed throughout the same period up to an oral dose of 400 mg per kg body weight.

Uses

The Commission E approved the use of horse chestnut seed for treatment of complaints found in pathological conditions of the veins of the legs (chronic venous insufficiency, CVI), for example, pain and a sensation of heaviness in the legs, cramps in the calves, pruritis, and swelling of the legs.

Note: Other non-invasive treatment measures prescribed by a physician, such as leg compresses, wearing of supportive elastic stockings, or cold water applications, must be observed under all circumstances.

Horse chestnut seed preparations are indicated for treatment of CVI, varicose veins, edema of the lower limbs, and hemorrhoids. It is reported to combine well with other herbs that improve peripheral circulation such as ginkgo leaf, gotu kola leaf, and bilberry fruit (Morgan and Bone, 1998).

Contraindications

None known.

Side Effects

Pruritis, nausea, and gastric complaints may occur in isolated cases after oral intake.

Use During Pregnancy and Lactation

No restrictions known.

Interactions with Other Drugs

None known.

Dosage and Administration

Unless otherwise prescribed:

Dry extract 5.0-8.0:1 (w/w): 250-312.5 mg, two times per day in delayed release form, corresponding to 100 mg escin daily. Take one dose in the morning and the other in the evening with ample liquids during meals.

References

Bisler, H., R. Pfeifer, N. Kluken, P. Pauschinger. 1986. Wirkung von Rosskastaniensamenextrakt auf die traskapillare filtration bei chronischer venoser insuffizien [Effects of horse-chestnut seed extract on transcapillary filtration in chronic venous insufficiency]. Dtsch Med Wochenschr 111(35):13211329.

Bombardelli, E. and P. Morazzoni. 1996. Aesculus hippocastanum L. Fitoterapia 67(6):483511.

Degenring, F.H. 1996. Aesculus Hipp. Semen for the treatment of venous blood flow disorders. Clinical Expert Report for Bioforce AG (unpublished).

Deutsches Arzneibuch (DAB 1997). 1997. Stuttgart: Deutscher Apotheker Verlag.

Diehm C., D. Vollbrecht, K Amendt, H.U. Comberg. 1992. Medical edema protectionClinical benefit in patients with chronic deep vein incompetence. A placebo-controlled double-blind study. Vasa 21(2):188192.

Diehm, C., H.J. Trampisch, S. Lange, C. Schmidt. 1996. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet 347(8997):292294.

Geissb hler, S. and F.H. Degenring. 1999. Treatment of chronic venous insufficiency with Aesculaforce Vein Gel. Schweiz Zschr Ganzheits Medizin 11:8287.

Greeske, K. and B.K. Pohlmann. 1996. [Horse chestnut seed extractan effective therapy principle in general practice. Drug therapy of chronic venous insufficiency] [In German]. Fortschr Med 114(15):196200.

Konoshima, T. and K.H. Lee. 1986. Antitumor agents, 82. Cytotoxic sapogenols from Aesculus hippocastanum. J Nat Prod 49(4):650656.

Leung, A.Y. and S. Foster. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2^nd ed. New York: John Wiley & Sons, Inc. 304306.

Morgan, M. and K. Bone. 1998. Professional Review: Horsechestnut. Medi Herb (65):14.

Newall, C.A., L.A. Anderson, J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press. 166167.

Pittler, M.H. and E. Ernst. 1998. Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol 134(11):13561360.

Shah, D., S. Bommer, F.H. Degenring. 1997. Aesculaforce in chronic venous insufficiency. Schweiz Zschr Ganzheits Medizin 9(2):8691.

Yoshikawa, M. et al. 1996. Bioactive saponins and glycosides. III. Horse chestnut. (1): The structures, inhibitory effects on ethanol absorption, and hypoglycemic activity of escins Ia, Ib, IIa, IIb, and IIIa from the seeds of Aesculus hippocastanum L. Chem Pharm Bull (Tokyo) 44(8):14541464.

Yoshikawa, M. et al. 1998. Bioactive saponins and glycosides. XII. Horse chestnut. (2): Structures of escins IIIb, IV, V and VI and isoescins Ia, Ib, and V, acylated polyhydroxyoleanene triterpene oligoglycosides, from the seeds of horse chestnut tree (Aesculus hippocastanum L., Hippocastanaceae). Chem Pharm Bull (Tokyo) 46(11):17641769.

Additional Resources

Boiadzhiev, T. et al. 1973. Experimental studies on the action of total extracts of Aesculus hippocastanum L. (horse chestnut) on cellular respiration. Eksp Med Morfol 12(1):1114.

Chan, E.H. et al. (eds.). 1985. Advances in Chinese Medicinal Materials Research. Singapore: World Scientific Pub. Co.

Longiave, D., C. Omini, S. Nicosia, F. Berti. 1978. The mode of action of aescin on isolated veins, relationship with PGF2. Pharmacol Res Commun 10(2):145152.

Popp, W. et al. 1992. Horse chestnut (Aesculus hippocastanum) pollen: a frequent cause of allergic sensitization in urban children. Allergy 47(4 pt. 2):380383.

This material was adapted from The Complete German Commission E MonographsTherapeutic Guide to Herbal Medicines. M. Blumenthal, W.R. Busse, A. Goldberg, J. Gruenwald, T. Hall, C.W. Riggins, R.S. Rister (eds.) S. Klein and R.S. Rister (trans.). 1998. Austin: American Botanical Council; Boston: Integrative Medicine Communications.

1) The Overview section is new information.

2) Description, Chemistry and Pharmacology, Uses, Contraindications, Side Effects, Interactions with Other Drugs, and Dosage sections have been drawn from the original work. Additional information has been added in some or all of these sections, as noted with references.

3) The dosage for equivalent preparations (tea infusion, fluidextract, and tincture) have been provided based on the following example:

• Unless otherwise prescribed: 2 g per day of [powdered, crushed, cut or whole] [plant part]
• Infusion: 2 g in 150 ml of water
• Fluidextract 1:1 (g/ml): 2 ml
• Tincture 1:5 (g/ml): 10 ml

4) The References and Additional Resources sections are new sections. Additional Resources are not cited in the monograph but are included for research purposes.

This monograph, published by the Commission E in 1994, was modified based on new scientific research. It contains more extensive pharmacological and therapeutic information taken directly from the Commission E.

Excerpt from Herbal Medicine: Expanded Commission E Monographs
Copyright 2000 American Botanical Council
Published by Integrative Medicine Communications
Available from the American Botanical Council.

This monograph, published by the Commission E in 1994, was modified based on new scientific research. It contains more extensive pharmacological and therapeutic information taken directly from the Commission E.