Ruscus / Muizedoorn

Introduction 

Butcher’s broom (Ruscus aculeatus) is a bushy evergreen subshrub that grows to 3 feet in height, with flat, leaf-like branches, disproportionate red berries, and greenish-white flowers in late winter and spring.1 It is native to the Mediterranean and Africa, from the Azores islands, west of Portugal, to Iran.2 The rhizome, or root, is the most common part of the plant used today.

History and Cultural Significance

The common name “butcher’s broom” came from Europe, where butchers would bundle the shrub into a broom to sweep and cleanse their cutting blocks, due to the stiffness of the material.3 (It was later discovered that the essential oil in the plant is antibacterial.) Europeans have been using the shrub as a laxative and diuretic for almost 2,000 years.2 Many cultures soaked the rootstock in water or wine to help alleviate abdominal complaints. In the first century CE, Greek physicians used butcher’s broom to treat kidney stones. In the 17th century, the English herbalist Nicholas Culpepper used butcher’s broom to help the healing of fractured bones. He recommended that patients take a decoction of the root (made by boiling the plant’s woody parts) orally along with spreading a poultice of the berries over the fracture.2

The root of butcher’s broom contains ruscogenen and neoruscogenin, which have been found to have anti-inflammatory characteristics and to cause contraction of veins. These properties have led to the modern uses of the plant as supportive care for chronic venous insufficiency (CVI), hemorrhoids, and varicose veins.2

The German Commission E approved the use of butcher’s broom rhizome extract for discomforts of CVI, such as pain and heaviness, as well as for cramps in the legs, itching, and swelling, and for supportive therapy for complaints of hemorrhoids, such as itching and burning.4 Similarly, the European Scientific Cooperative on Phytotherapy (ESCOP) recommended solid or liquid extracts of the dried, whole or fragmented rhizome for supportive therapy for symptoms of CVI and hemorrhoids.5 The European Medicines Agency (EMEA) finalized its Community Herbal Monograph in 2008 for the registration of butcher’s broom products as traditional herbal medicines.6 Butcher’s broom medicinal products, in compliance with the quality standards set out by the European Pharmacopoeia,7 may be registered and labeled as traditional herbal medicinal products (THMPs) for the relief of symptoms of discomfort and heaviness of legs related to minor venous circulatory disturbances and symptomatic relief of itching and burning associated with hemorrhoids,6 with the noted limitation that such application is based solely on “long-standing use.”

Modern Research

Human studies have investigated formulations containing butcher’s broom for their effects on insufficient blood flow to the lower limbs, including in chronic venous disease (CVD) and/or CVI. CVD of the lower limbs can be recognized by symptoms such as varicose veins and venous ulcers, as well as edema, venous eczema, hyperpigmentation of the skin of the ankle, atrophie blanche (white scar tissue), and lipodermatosclerosis.8 CVD is often graded according to 7 classes of CEAP classification (e.g., clinical, etiologic, anatomical, and pathophysiological), which range from C0 to C6. The term CVD is applied to the full spectrum of symptoms from C0 to C6, whereas CVI is generally restricted to more severe disease (C4 to C6).

Studies include one in 1987 that studied butcher’s broom in combination with trimethylhesperidine chalcone and ascorbic acid for the treatment of lower limb venous disease,9 one in 1988 that investigated its ability to treat lower limb venous disease in patients with chronic phlebopathy (venous insufficiency) when taken in combination with hesperidin and ascorbic acid,10 one in 1989 that tested its effects on venous tone and capillary sealing when taken in combination with hesperidine methyl chalcone,11 and two in 1999 that assessed the effect of a combination of Ruscus extract (150 mg) and hesperidin methyl chalcone (150 mg) and ascorbic acid (100 mg) (Cyclo 3 Fort®, Pierre Fabre Medicament, Paris, France) on uncomplicated venous insufficiency and superficial varicose veins.12,13

Patients in a 2000 trial studying Cyclo 3 Fort for CVI experienced a significant reduction of symptoms and had a more favorable opinion of butcher’s broom than rutoside.14 Of the 80 participants, the treatment group took 2 capsules per day for 90 days, and the preparation was rated as excellent by 81.6% of the treating physicians.

In a 2007 study, 124 patients suffering from CVI were given 2 capsules of a combination product containing 150 mg butcher’s broom, 150 mg hesperidin methylchalcone (HMC) and 100 mg ascorbic acid (Fabroven®/Cyclo 3 Fort®; Pierre Fabre Ibérica; Barcelona, Spain) daily for 8 weeks.15 Improvement was seen in all patients, but the authors stated that although the early results were promising, symptom changes beyond the 8 weeks with treatment need to be clarified.

A 2008 study evaluated the effect of butcher’s broom, hesperidine methylchalcone (flavonoid), and vitamin C (Cirkan®, Pierre Fabre Santé; Boulogne, France) on women with CVD.16 After 4 weeks, the patients treated with Cirkan had experienced significant improvement in capillary morphology and capillary limb diameter, while the control group and the group treated only with elastic compression stockings did not.

A recent quality of life (QoL) study followed 917 Mexican patients (mostly women over 40 who were sedentary, overweight, or obese) suffering from CVD.17 Patients were given 1 capsule daily of Cyclo 3 Fort for 12 weeks. Evaluation of QoL using 2 auto-questionnaires showed that all symptoms improved, with lower limb heaviness and lower limb pain improving the most at 83% and 81%, respectively, and more so in older patients.

Studies on butcher’s broom alone for its effect on CVI are fewer in number. A long-term study published in 1991 studied 141 patients with CVI who took 3 capsules of Ruscus extract (type and manufacturer unspecified) twice daily for 4 weeks, then 2 capsules twice daily for 8 weeks.18 In all patients taking the extract, there was a decrease in foot and ankle volume after 13 weeks while the patients taking placebo experienced increased volume. The authors concluded that the reparation was a slow process and incomplete at the end of the study.

In 2003, 56 women suffering from CVI completed a study in which they were given 72-75 mg of a dry extract of butcher’s broom rhizome/root (Fagorutin®Ruscus Kapseln, GlaxoSmithKline Consumer Healthcare GmbH, Herrenberg, Germany) daily for 12 weeks.19

Another 54 women were given placebo. Measurement of leg volume (indicative of edema) and symptoms were evaluated after 4, 8, and 12 weeks of treatment. All parameters improved in the butcher’s broom group and remained the same in general for the placebo group. The authors concluded that butcher’s broom was well tolerated and effective for CVI of Widmer grades I and II (mild to moderate stages).

Additionally, butcher’s broom has been studied for its potential vein-constricting action when applied locally. In a 1990 study, a Ruscus extract cream (specifics unknown) applied topically decreased the diameter of the femoral vein an average of 1.25 mm in 2.5 hours.20 A 2003 study used a cream made of butcher’s broom and yellow sweet clover (Melilotus officinalis, Fabaceae), (formulation unknown, FLEBS Crema®, Laboratoires Pierre Fabre, Castres Cedex, France) that, applied to both legs each day for 3 weeks, showed improvement in swelling, pain, and itching.21

A single small trial in 1996 suggested that butcher’s broom might be helpful in preventing diabetic retinopathy.22 Twenty patients, most suffering from non-insulin dependent diabetes (type 2) with non-proliferative diabetic retinopathy, were given 1 capsule of 0.0375 g of butcher’s broom dry extract 2 times a day (Fagorutin-Ruscus Kapseln®, GlaxoSmithKline Consumer Healthcare GmbH, Herrenberg, Germany) for 3 months. Regression of diabetic retinopathy was detected in 23.1% of patients and no cases of disease progression were seen.

In one randomized, double-blind trial in 1991, 20 women aged 18-50 years suffering from premenstrual syndrome were given 2 capsules per day for 90 days of Cyclo 3 Fort. The butcher’s broom group experienced reduced symptoms of premenstrual syndrome, including mastalgia, mood disorders, and ankle edema.23

Butcher’s broom was shown to be efficacious in treating hemorrhoids in a study of 124 patients, in which the patients were given 6 capsules per day of Cyclo 3 Fort for 3 days, followed by 4 capsules per day for 4 days. Sixty-nine percent of the patients rated butcher’s broom as having a good or excellent effect, and 75% of the treating physicians rated it similarly.24

Future Outlook

TRAFFIC, the wildlife trade monitoring network that is a joint program of the World Wildlife Fund (WWF) and the International Union for the Conservation of Nature (IUCN), stated in 1998 that wild collection of butcher’s broom in Turkey resulted in a harvest of 2,000 tons of fresh roots per year, or 400 tons of dried material, primarily for export.25 The species had become locally extinct in certain areas of Turkey owing to over-collection and is among the 10 most threatened medicinal plants in trade in Turkey. At the time, the collection of the species was subject to restrictions in France, Bulgaria, Hungary, and Spain, indicating that the species is threatened in these countries also.25 In Spain, this protection takes the form of limiting the amount that may be harvested.26

In 2002, in a working group report, the International Plant Genetic Resources Institute stated that R. aculeatus was one of the plants sold on the Serbian market for which no cultivation information was available.27 As of 2006, wild butcher’s broom was protected by law from collection in Romania as it is considered a “monument of nature.”28

In Hungary, where butcher’s broom was once threatened by international trade, the situation has changed since that country joined CITES (The Convention on International Trade in Endangered Species) and protected the species.29 Authorities have pledged to update the list of protected species regularly so the threats by trade can be addressed quickly.

The 9th meeting of the Convention on Biological Diversity (May 19-30, 2008) produced a Global Strategy for Plant Conservation (GSPC) and recommended that parties develop strategies and action plans to achieve relevant biodiversity target and goals.30 The GSPC target addressing butcher’s broom implemented action plans and disseminated methods to ensure that it not be endangered by trade within Europe.

References


Butcher's Broom Uses and Pharmacology

Lower Limb Venous Disease

Animal data

In dogs, an extract of the root was shown to cause a dose-dependent increase in the contraction of isolated veins. These contractions were inhibited by the alpha-adrenergic blocking agent phentolamine, suggesting that compounds in Ruscus activated alpha-1 and alpha-2 receptors in smooth muscle. Ruscus had no influence on prostaglandin levels in these tests. 13 Prazosin, an alpha-1-adrenoceptor antagonist, also reduced the activity of Ruscus extract. 14 Topical application of the extract on hamster cheek pouch microvasculature displayed concentration- and temperature-dependent responses in the vessels. 15

Clinical data

In humans, RAES , a venotropic drug containing Ruscus extract, has been shown to be effective in improving the signs and symptoms of lower limb venous disease in patients with chronic phlebopathy. 16 RAES is composed of 16.5 mg Ruscus extract, 75 mg hesperidin, and 50 mg ascorbic acid. 16 The effectiveness and tolerability of this product was evaluated during a 2-month, double-blind, placebo-controlled, crossover trial involving 40 patients with chronic phlebopathy of the lower limbs. A trend toward improvement was noted among treated patients, although statistical significance was not reached. In particular, edema, itching, and paresthesias improved, as did a feeling of limb heaviness and cramping. In another randomized, double-blind study, 18 healthy volunteers applied 4 to 6 g of a cream containing 64 to 96 mg of Ruscus extract to their legs; a reduction in the diameter of the femoral vein was noted ( P = 0.014). 17

Extracts of Ruscus have been included in commercial therapeutic agents designed for the management of venous insufficiency. The most commonly known oral formulation, Cyclo 3 Fort , is composed of R. aculeatus extract, hesperidin methylchalcone, and ascorbic acid. In France, Ruscus extract is the standard treatment in preventing postoperative thrombosis. 1 Ruscus has venotonic properties, such as reducing venous capacity and pooling of blood in the legs. It also has a protective effect on capillaries, the vascular endothelium, and smooth muscle. 1

Formulations of suppositories containing 100 mg of dry Ruscus extract are being investigated for the treatment of hemorrhoids and other venous diseases. A 100 mg extract contains 0.5 mg of active ruscogenins. 18

Orthostatic Hypotension

Animal data

As orthostatic hypotension generally worsens under hot environmental conditions, Ruscus extract is unique in that under these conditions, the response of cutaneous veins improves greatly. 14

Clinical data

Ruscus is used to treat orthostatic hypotension and does not cause supine hypertension like other related drug therapies. 1 It is noted in several references that treatment of venous diseases is best accomplished using Ruscus extracts along with other nonpharmacologic therapies.

Cytotoxic

Several studies indicate that compounds found in butcher's broom may possess cytotoxic activity. Researchers have found cytotoxic activity in aculeoside A; it exhibited inhibitory activity against HL-60 cancer cell growth with an IC 50 of 0.48 mcg/mL. 19 A furanosterol and its corresponding spirostanol have exhibited inhibition of HL-60 cells in vitro. The presence of acetyl and 2-hydroxy-3-methyl pentanoyl groups attached to the diglycoside moiety is suspected to contribute to the observed cytostatic activity. 20

Cytotoxic activity also has been demonstrated with Ruscus diglycoside and its corresponding saponin in culture. 8

Anti-inflammatory

The combined action of flavonoids, sterols, and proteolytic enzymes found in the root has been shown to reduce dextran and carrageenan-induced rat paw edema, indicating that the extract has some anti-inflammatory activity. 21 This mixture of compounds was administered intraduodenally, thereby reducing the possibility of inactivation by stomach acids.

Diuretic

Glycolic acid found in the plant is credited for short-term diuretic activity. 1

Other uses

Researchers have found that when a Ruscus extract is applied topically, a dose-dependent inhibition of the macromolecular permeability-increasing effect of histamine occurs. 22 Ruscus extract given IV (5 mg/kg) inhibits the macromolecular permeability-increasing effect of bradykinin, leukotriene B4, and histamine. 22 Ruscogenins are ineffective on hyaluronidase activity but show exceptional antielastase activity. 23

Referenties

15. Bouskela E, Cyrino FZ, Marcelon G. Effect of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation. J Cardiovasc Pharmacol . 1993;22:221-224.

16. Cappelli R, Nicora M, Di Perri T. Use of extract of Ruscus aculeatus in venous disease in the lower limbs. Drugs Exp Clin Res . 1988;14:277-283.

17. Berg D. Venous constriction by local administration of Ruscus extract [in German]. Fortschr Med . 1990;108:473-476.

18. Bouskela E, Cyrino FZ, Marcelon G. Inhibitory effect of Ruscus extract and of the flavonoid hesperidine methylchalcone on increased microvascular permeability induced by various agents in the hamster cheek pouch. J Cardiovasc Pharmacol . 1993;22:225-230.

19. Mimaki Y, Kuroda M, Kameyama A, Yokosuka A, Sashida Y. Aculeoside B, a new bisdesmosidic spirostanol saponin from the underground parts of Ruscus aculeatus . J Nat Prod . 1998;61:1279-1282.

20. Mimaki Y, Kuroda M, Kameyama A, Yokosuka A, Sashida Y. New steroidal constituents of the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells. Chem Pharm Bull . 1998;46:298-303.

21. Tarayre JP, Lauressergues H. The anti-edematous effect of an association of proteolytic enzymes, flavonoids, sterolic heteroside of Ruscus aculeatus and ascorbic acid [in French]. Ann Pharm Fr . 1979;37:191-198.

22. Peneva B, Krasteva I, Nikolov S, Minkov E. Formulation and in vitro release of suppositories containing dry extract of Ruscus aculeatus L. Pharmazie . 2000;55:956.

23. Facino RM, Carini M, Stefani R, Aldini G, Salbene L. Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedra helix , Aesculus hippocastanum , and Ruscus aculeatus : factors contributing to their efficacy in the treatment of venous insufficiency. Arch Pharm . 1995;328:720-724.


RUSCUS  ACULEATUS  L. Muizedoorn 

Monografie uit het cursusboek van de opleiding

ALGEMENE  EN  BOTANISCHE  INFORMATIE

MATERIA  MEDICA

SAMENSTELLING

FARMACOLOGIE

INDICATIE

RECEPTUUR

GESCHIEDENIS  EN  WETENSCHAPPELIJK  ONDERZOEK

Butcher's broom is an evergreen shrub native to Mediterranean Europe and Africa from the Azores islands, west of Portugal, to Iran in southwestern Asia (Tyler, 1987; Weiss, 1988). It has been used in  European  medicine  for  nearly  two  thousand  years  as  a  laxative  and  diuretic  agent  to  treat urinary, gastrointestinal, and reproductive disorders (Foster and Tyler, 1999).  

-Dioscorides reported its laxative effects as well as its use as a treatment for kidney stones.  -Nicholas Culpepper, the seventeenth century English herbalist, reported that the decoction  of the root taken orally, and a poultice of the berries applied topically, assisted in the knitting of fractured bones.  

-Leclerc - Précis de Phytothérapie (1976): veel gebruikt in Frankrijk -Leclerc  -Le Fragon  ou Petit  Houx: son emploi dans le traitement  des hémorroides. Revue de phytothérapie 1953.  

-Traditionally,  the  rootstock  was  decocted  in  water  or  wine  as  a  treatment  for  abdominal complaints (Weiss, 1988).  Commission E  approved  its  use  as  a supportive therapy  for  discomforts  of chronic  venous  insufficiency, such  as  pain  and heaviness, as well as cramps in the legs, itching, and swelling. It is also approved as a supportive therapy for complaints of hemorrhoids, such as itching and burning.  

Referenties 

-———. 1993. Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation. J Cardiovasc Pharmacol 22(2):221–224.  

-Archimowicz-Cyrylowska,  B.  et  al.  1996.  Clinical  effect  of  buckwheat  herb,  ruscus  extract  and  troxerutin  on retinopathy and lipids in diabetic patients. Phytother Res 10(8): 659–662. 

 -Berg,  D.  1990.  Venenkonstriktion  durch  lokale  Anwendung  von  Ruscusextrakt.  [Venous  constriction  by  local administration of Ruscus extract]. Fortschr Med 108(24):473–476. 

 -Bouskela,  E.,  F.Z.  Cyrino,  G.  Marcelon.  1994.  Possible  mechanisms  for  the  inhibitory  effect  of  Ruscus  extract  on increased  microvascular  permeability  induced  by  histamine  in  hamster  cheek pouch.  J  Cardiovasc  Pharmacol 24(2):281–285. 

 -Facino,  R.M.,  M.  Carini,  R.  Stefani,  G.  Aldini,  L.  Saibene.  1995.  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. Arch Pharm (Weinheim) 328(10):720–724.