Research Update:Butcher's Broom or Ruscus aculeatus.

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   Phytochemical info of Butcher's Broom or Ruscus aculeatus

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 Definition:Butcher's Broom or Ruscus aculeatus are majorly composed of
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   Research Update:Butcher's Broom or Ruscus aculeatus.

  Clinical and capillaroscopic evaluation in the treatment of chronic venous insufficiency with Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid in venous insufficiency treatment of ambulatory patients.:Int Angiol. 2007 Dec;26(4):378-384.Aguilar Peralta GR, Ar¨¦valo Gardoqui J, Llamas Mac¨ªas FJ, Navarro Ceja VH, Mendoza Cisneros SA, Mart¨ªnez Mac¨ªas CG. Unit of Angiology and Vascular Surgery ? HUMVASCULAR ? Guzman City, Jalisco, Mexico gaguiper@prodigy.net.mx.

 AIM: Clinical and capillaroscopic evaluation of an association of Ruscus aculeatus, hesperidin methylchalcone (HMC) and ascorbic acid in chronic venous insufficiency METHODS: A prospective, multicenter and open clinical study. Chronic venous insufficiency patients were studied using clinical, etiological, anatomical, physiological classification (CEAP) symptom scale. Symptomatology, CEAP scale, and baseline, 2-, 4-, 6- and 8-week skin capillaroscopy were assessed. Treatment consisted of two capsules per day of Ruscus aculeatus 150 mg/HMC 150 mg/ascorbic acid 100 mg during 8 weeks. RESULTS: A total of 124 patients were studied, 109 female (89.28%), with a mean age of 52.5 (33-80+9.8). Initial intense reports were 79% pain, 85% heaviness, 74% cramps, 82% edema, decreasing to 20%, 12%, 8% and 14%, respectively, within two weeks, and symptomatology being absent at the end of treatment. Capillaroscopy changes at treatment completion were: 98% to 20% inter-capillary fluid decrease; 80% to 20% efferent loop thickening; 5% to 2% peri-capillary bed, and 5% to 4% mega-capillaries. CONCLUSION: Severe symptom decrease started from the second week until there were no symptoms at the end of treatment. It is the first time morphologic changes were observed in chronic venous insufficiency through capillaroscopy following a pharmacological intervention. Capillary-level effect was proportional to symptom decrease. Improvement was seen from the second week of treatment.

  Expression patterns of class I KNOX and YABBY genes in Ruscus aculeatus (Asparagaceae) with implications for phylloclade homology.:Dev Genes Evol. 2007 May;217(5):363-72. Epub 2007 Apr 12.

 STM (RaSTM) and YAB2 (RaYAB2) homologues were isolated from Ruscus aculeatus (Asparagaceae, monocots), and their expressions were analyzed by real-time polymerase chain reaction (PCR) to assess hypotheses on the evolutionary origin of the phylloclade in the Asparagaceae. In young shoot buds, RaSTM is expressed in the shoot apex, while RaYAB2 is expressed in the scale leaf subtending the shoot bud. This expression pattern is shared by other angiosperms, suggesting that the expression patterns of RaSTM and RaYAB2 are useful as molecular markers to identify the shoot and leaf, respectively. RaSTM and RaYAB2 are expressed concomitantly in phylloclade primordia. These results suggest that the phylloclade is not homologous to either the shoot or leaf, but that it has a double organ identity.

  Chromatographic behaviour of steroidal saponins studied by high-performance liquid chromatography-mass spectrometry.:J Chromatogr A. 2007 May 4;1148(2):177-83. Epub 2007 Mar 15.Kite GC, Porter EA, Simmonds MS.Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, UK. g.kite@kew.org

 The chromatographic behaviour of steroidal saponins found in Anemarrhena asphodeloides, Asparagus officinalis, Convallaria majalis, Digitalis purpurea and Ruscus aculeatus was studied by HPLC-MS using a C-18 reversed-phase column and aqueous acetonitrile or aqueous methanol mobile phase gradients, with or without the addition of 1% acetic acid. The behaviour was compared to that of triterpene saponins found in Aesculus hippocastanum, Centella asiatica, Panax notoginseng and Potentilla tormentilla. Inclusion of methanol in the mobile phase under acidic conditions was found to cause furostanol saponins hydroxylated at C-22 to chromatograph as broad peaks, whereas the peak shapes of the spirostanol saponins and triterpene saponins studied remained acceptable. In aqueous methanol mobile phases without the addition of acid, furostanol saponins chromatographed with good peak shape, but each C-22 hydroxylated furostanol saponin was accompanied by a second chromatographic peak identified as its C-22 methyl ether. Methanolic extracts analysed in non-acidified aqueous acetonitrile mobile phases also resolved pairs of C-22 hydroxy and C-22 methoxy furostanol saponins. The C-22 methyl ether of deglucoruscoside was found to convert to deglucoruscoside during chromatography in acidified aqueous acetonitrile, or by dissolving in water. Poor chromatography of furostanol saponins in acidified aqueous methanol is due to the interconversion of the C-22 hydroxy and C-22 methoxy forms. It is recommended that initial analysis of saponins by HPLC-MS using a C-18 stationary phase is performed using acidified aqueous acetonitrile mobile phase gradients. The existence of naturally-occurring furostanol saponins methoxylated at C-22 can be investigated with aqueous acetonitrile mobile phases and avoiding methanol in the extraction solvent.

  The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella asiatica, Ruscus aculeatus and Galphimia glauca cultured plants.:Phytochemistry. 2006 Sep;67(18):2041-9. Epub 2006 Jul 28.Mangas S, Bonfill M, Osuna L, Moyano E, Tortoriello J, Cusido RM, Pi?ol MT, Palaz¨®n J.Laboratorio de Fisiolog¨ªa vegetal, Facultad de Farmacia, Universidad de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain.

 Considering that exogenously applied methyl jasmonate can enhance secondary metabolite production in a variety of plant species and that 2,3-oxidosqualene is a common precursor of triterpenes and sterols in plants, we have studied Centella asiatica and Galphimia glauca (both synthesizing triterpenoid secondary compounds) and Ruscus aculeatus (which synthesizes steroidal secondary compounds) for their growth rate and content of free sterols and respective secondary compounds, after culturing with or without 100 microM methyl jasmonate. Our results show that elicited plantlets of G. glauca and to a higher degree C. asiatica (up to 152-times more) increased their content of triterpenoids directly synthesized from 2,3-oxidosqualene (ursane saponins and nor-seco-friedelane galphimines, respectively) at the same time as growth decreased. In contrast, the free sterol content of C. asiatica decreased notably, and remained practically unaltered in G. glauca. However, in the case of R. aculeatus, which synthesizes steroidal saponins (mainly spirostane type) indirectly from 2,3-oxidosqualene after the latter is converted to the plant phytosterol-precursor cycloartenol, while the growth rate and free sterol content clearly decreased, the spirostane saponine content was virtually unchanged (aerial part) or somewhat lower (roots) in presence of the same elicitor concentration. Our results suggest that while methyl jasmonate may be used as an inducer of enzymes involved in the triterpenoid synthesis downstream from 2,3-oxidosqualene in both C. asiatica and G. glauca plantlets, in those of C. asiatica and R. aculeatus it inhibited the enzymes involved in sterol synthesis downstream from cycloartenol.

  Effect of organogenesis on steroidal saponin biosynthesis in calli cultures of Ruscus aculeatus.:Fitoterapia. 2006 Apr;77(3):216-20. Epub 2006 Feb 23.Palaz¨®n J, Moyano E, Bonfill M, Osuna LT, Cusid¨® RM, Pi?ol MT.Laboratorio de Fisiolog¨ªa Vegetal, Facultad de Farmacia, Universidad de Barcelona, Avenida Diagonal 643, 08028 Barcelona, Spain. javierpalazon@ub.edu

 Calli cultures derived from Ruscus aculeatus rhizomes were investigated for their potential to biosynthesize saponins. The capacity of undifferentiated tissues to form steroidal saponins is very limited, but when the calli developed organogenesis, mainly aerial shoots and roots, the saponin production increased significantly. Plantlets regenerated from aerial shoots of Ruscus calli showed a saponin pattern similar to that of the callus cultures but the levels of saponins found in the aerial part and roots were significantly greater.


  Determination of anthocyanins in Ruscus aculeatus L. berries.:J Agric Food Chem. 2005 Jan 26;53(2):475-9.Longo L, Vasapollo G.Dipartimento di Ingegneria dell'Innovazione, Universit¨¤ di Lecce, via per Arnesano km 1, 73100 Lecce, Italy.

 Red berries of Ruscus aculeatus L., a wild shrub typical of Mediterranean Europe and Africa, were investigated for the first time in order to determine the profile of anthocyanins. The pigments were extracted from the skins of the berries with 0.1% HCl in methanol, purified using a C-18 solid phase cartridge, and identified by means of high-performance liquid chromatography (HPLC)-diode array detection-mass spectrometry analysis. Information from HPLC profiles, saponification, and acid hydrolysis of the anthocyanins showed that the major anthocyanins were pelargonidin 3-O-rutinoside (64%), pelargonidin 3-O-glucoside (16%), and pelargonidin 3-O-trans-p-coumarylglucoside (13%). The attractive color of R. aculeatus berries and the great abundance of the plant in the south of Italy make these berries a new and promising source of natural colorants.

  Meta-analysis of clinical trials of Cyclo 3 Fort in the treatment of chronic venous insufficiency.:Int Angiol. 2003 Sep;22(3):250-62.Boyle P, Diehm C, Robertson C.Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. peter.boyle@ieo.it

 AIM: Chronic venous insufficiency (CVI) of the lower limbs is a major cause of morbidity and varicose veins affect 20% to 60% of adults in the western world. The treatment of patients with CVI attempts to reduce both clinical symptoms and the development of chronic venous disease. A meta-analysis using data from all clinical trials and studies of Cyclo 3 Fort, a combination of root extract of the Ruscus aculeatus plant (150 mg per capsule), hesperidin methyl chalcone (150 mg) and ascorbic acid (100 mg), was carried out to estimate the overall effect on the symptoms and severity of chronic venous insufficiency. METHODS: The meta-analysis included 20 placebo controlled, randomised, double blind studies and 5 randomised studies against a comparator drug. There were 6 single arm studies of Cyclo 3 Fort alone with no placebo arm. In all studies the response to Cyclo 3 Fort was compared to baseline values. In total there was information from 10,246 subjects. RESULTS: On a 4 point symptom severity scale, where 0 corresponds to no symptoms and 3 to severe symptoms, Cyclo 3 Fort significantly reduces the severity of pain by 0.44 (0.12) points; cramps 0.26 (0.08), heaviness 0.53 (0.11), and paraesthesia 0.29 (0.10) compared to placebo. There is also a significant reduction in venous capacity of 0.70 (0.19) ml/100 ml with Cyclo 3 Fort compared to placebo. We also found reductions in the severity of oedema 0.43 (0.20) points, and decreases in calf and ankle circumference, 0.73 (0.37) cms and 1.17 (0.83) cm, respectively, among patients treated with Cyclo 3 Fort compared to placebo which were not statistically significant. CONCLUSION: Despite questions surrounding the variability of data quality and sample size of some of the studies, we conclude that in patients with CVI Cyclo 3 Fort significantly reduces the severity of the symptoms compared to placebo. This study is a strong and objective demonstration of the clinical efficacy of Cyclo 3 Fort in treating patients with CVI.

  Identification of Ruscus steroidal saponins by HPLC-MS analysis.:Fitoterapia. 2002 Dec;73(7-8):583-96. Erratum in: Fitoterapia. 2003 Jun;74(4):423.de Combarieu E, Falzoni M, Fuzzati N, Gattesco F, Giori A, Lovati M, Pace R.Indena SpA, Research and Development Laboratories, Via Don Minzoni 6, 20090 Settala (MI), Italy.

 A novel HPLC-UV method has been developed for the fingerprint analysis of the steroidal saponins in the rhizomes of three Ruscus species (Ruscus aculeatus, Ruscus hypoglossum and Ruscus colchicus). Saponins were identified by HPLC-ESI-MS. During the study a new major saponin was detected in the rhizomes of R. hypoglossum and R. colchicus. The structure of the new compound was defined as 1-O-[alpha-L-rhamnopyranosyl-(1-->2)-6-O-acetyl-beta-D-galactopyranosyl]-1beta,3beta,22xi,26-tetrahydroxy-furost-5(6)-en-26-O-beta-D-glucopyranoside (8) by spectral analysis. Copyright 2002 Elsevier Science B.V.

  Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency.:Arzneimittelforschung. 2002;52(4):243-50.Vanscheidt W, Jost V, Wolna P, L¨¹cker PW, M¨¹ller A, Theurer C, Patz B, Gr¨¹tzner KI.Rheintalklinik, Bad Krozingen, Germany.

 Extracts from Butcher's broom rhizome (Ruscus aculeatus) have been widely used in the oral treatment of lower leg edema in patients with chronic venous insufficiency. The aim of the present multi-center, double-blind, randomized, placebo-controlled trial was to confirm the efficacy and safety of a ruscus extract (Fagorutin Ruscus Kapseln) according to the latest scientific standards. 166 women suffering from chronic venous insufficiency (Widmer grade I and II, CEAP (Clinical signs, Etiological classification, Anatomic distribution, Pathophysiology) 3-4) were included. The data of 148 patients (30-89 years, 150-182 cm height, 49-97 kg body weight) with a mean disease duration of 14.6 years in the ruscus extract group and 15.1 years in the placebo group were eligible for the intent-to-treat-analysis. The primary parameter was the area under baseline of the leg volume changes over 12 weeks (AUB0-12). Secondary parameters were the changes in circumference of the lower leg and the ankle, changes in subjective symptoms and quality of life, the overall efficacy and tolerability and safety parameters. The study was carried out according to the guidelines for testing drugs for chronic venous insufficiency. There were significant differences between the treatment groups ruscus and placebo for the AUB0-12 (-827 ml x day), for the change of leg volume after 8 and 12 weeks of treatment (-16.5 ml and -20.5 ml), for changes in ankle and leg circumferences after 8 and 12 weeks of treatment, and for the changes in subjective symptoms, heavy tired legs and sensation of tension (week 12). For the changes in the symptoms heavy lower legs, sensation of tension, and tingling sensation a significant positive correlation with the changes in leg volume was shown. Overall assessment of efficacy was significantly better for ruscus extract compared to placebo. Overall tolerability for both treatments was assessed as good and very good. Of all 48 adverse events occurring in both treatment groups, 22 were reported in the ruscus group, one of them was considered to be related to the study medication (unlikely). Considering the study duration of three months it is concluded, that ruscus extract, in the recommended daily dosage according to the German monograph, is a safe and effective treatment for patients suffering from chronic venous insufficiency.

  Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report.:J Altern Complement Med. 2000 Dec;6(6):539-49.Redman DA.American University, Washington, DC, USA.

 CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects large groups of the population with autonomic insufficiency--the elderly; patients with diabetes, Parkinson's disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders. OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy for OH and encourage further studies on the efficacy of Ruscus for OH patients. DESIGN: Review of OH and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its mechanism of action, and its suitability as a therapeutic agent for treatment of OH. RESULTS: A review of the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other therapy can offer--alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an extremely safe, inexpensive, over-the-counter botanical medicine. CONCLUSION: With proven phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus shows great promise for ameliorating the symptoms of OH and improving the quality of life for large groups in the population. It clearly deserves to be the object of wider research and study as a treatment for OH.


  Pharmacological assessment of adrenergic receptors in human varicose veins.:Int Angiol. 2000 Jun;19(2):176-83.Miller VM, Rud KS, Gloviczki P.Department of Surgery, Mayo Clinic and Foundation, Rochester, MN 55905, USA. miller.virginia@mayo.edu

 BACKGROUND: Experiments were to characterize pharmacologically adrenergic receptors in human varicose veins to the natural transmitter norepinephrine and to an extract of Ruscus. METHODS: Greater saphenous veins and varicose tributaries from patients undergoing elective surgery for primary varicose disease and portions of greater saphenous veins from patients undergoing peripheral arterial reconstruction (control) were suspended for the measurement of isometric force in organ chambers. Concentration response curves were obtained to norepinephrine or the extract of Ruscus aculeatus in the absence and presence of selective antagonists of alpha, and alpha2 adrenergic receptors. RESULTS: Norepinephrine and Ruscus extract caused concentration-dependent contractions in all veins. Contractions to norepinephrine were greater in control veins than in varicose tributaries. Contractions to the extract were greater in varicose tributaries than in greater saphenous veins from varicose patients. Contractions to norepinephrine were reduced similarly by alpha and alpha2-adrenergic agonists in control and varicose veins but to a greater extent by alpha2-blockade in greater saphenous veins from varicose patients. Contractions to Ruscus extract were not reduced by alpha-adrenergic blockade in control veins but were reduced by alpha2-adrenergic blockade in varicose veins. CONCLUSIONS: These results suggest a differential distribution of alpha adrenergic receptors on greater saphenous veins from non-varicose patients compared to those with primary varicose disease. Venotropic agents from plant extract probably exert effects by way of multiple receptor and non-receptor mediated events.

  An open-label, randomised multicentre study comparing the efficacy and safety of CYCLO 3 FORT versus hydroxyethyl rutoside in chronic venous lymphatic insufficiency.:Int Angiol. 1999 Dec;18(4):337-42.Beltramino R, Penenory A, Buceta AM.Society of Phlebology of Tucuman, Argentina.

 BACKGROUND: The present study was designed to compare the safety and efficacy of a combination of Ruscus aculeatus, hesperidin methyl chalcone and ascorbic acid (CYCLO 3 FORT) versus that of hydroxyethyl rutoside in the treatment of chronic venous lymphatic insufficiency. METHODS: This open-label, randomised multicentre study was conducted on outpatients treated for 90 days. The patients were from three different regions of Argentina. Eighty patients, men and women, 30 to 70 years of age, with symptoms of chronic venous lymphatic insufficiency, i.e. heavy, tired, swollen, or painful legs were enrolled and assigned to two groups: one group treated with CYCLO 3 FORT, the other with rutoside. The symptoms were assessed at baseline, and after 30, 60, and 90 days. The patient himself was asked to assess subjective symptoms, the physician measured the size of the affected limbs. The efficacy was rated on a 3-point scale and safety was evaluated by the number of side effects. RESULTS: The result data show that when all patients were comparable at baseline, after 90 days, those treated with CYCLO 3 FORT reported more rapid and more complete regression of symptoms than those in the rutoside group, a statistically significant difference (p<0.01). Likewise, a significant reduction in affected limb size was observed in both groups but persisted after 90 days in the CYCLO 3 FORT group only (p<0.01). CONCLUSIONS: As a conclusion : CYCLO 3 FORT was safe and more effective than rutoside in the treatment of venous lymphatic insufficiency. And the CYCLO 3 FORT efficacy is probably associated with its unique mechanism of action.

  Effect of Ruscus extract and hesperidin methylchalcone on hypoxia-induced activation of endothelial cells.:Int Angiol. 1999 Dec;18(4):306-12.Bouaziz N, Michiels C, Janssens D, Berna N, Eliaers F, Panconi E, Remacle J.Laboratoire de Biochimie et Biologie Cellulaire--Facult¨¦s Universitaires Notre-Dame de la Paix--Namur, Belgium.

 BACKGROUND: Ruscus aculeatus extract and the flavonoid hesperidin methylchalcone (HMC) are drugs used in the treatment of chronic venous insufficiency. METHODS: In the present study, we investigated their effects on the activation of endothelial cells by hypoxia, a condition which mimics venous blood stasis. RESULTS: We observed that Ruscus extract was able to inhibit the activation of endothelial cells by hypoxia: the decrease in ATP content, the activation of phospholipase A2 as well as the subsequent increase in neutrophil adherence with a maximal protection obtained at 50 microg/ml. HMC was also able to inhibit the hypoxia-induced decrease in ATP content. Furthermore, the effects of Ruscus extract and of HMC on this decrease seem to be additive. CONCLUSIONS: The biochemical mechanism evidenced in this work might explain some of the beneficial therapeutic effects of these products in the treatment of chronic venous insufficiency patients.

  Antifungal activity of plant extracts against dermatophytes.:Mycoses. 1999;42(11-12):665-72.Ali-Shtayeh MS, Abu Ghdeib SI.Department of Biological Sciences, An-Najah National University, Nablus, Palestine.

 The aqueous extracts (15 micrograms ml-1 medium) of 22 plants used in folkloric medicine in Palestine were investigated for their antifungal activity and minimum inhibitory concentrations (MICs) against nine isolates of Microsporum canis, Trichophyton mentagrophytes and Trichophyton violaceum. The extract of the different plant species reduced colony growth of the three dermatophytes by 36 to 100% compared with the control treatment. Antimycotic activity of the extract against the three dermatophytes varied significantly (P < 0.05) between test plants. Extracts of Capparis spinosa and Juglans regia completely prevented growth of M. canis and T. violaceum. The most active extracts (90-100% inhibition) were those of Anagallis arvensis, C. spinosa, J. regia, Pistacia lentiscus and Ruta chalapensis against M. canis; Inula viscosa, J. regia and P. lentiscus against T. mentagrophytes; and Asphodelus luteus, A. arvensis, C. spinosa, Clematis cirrhosa, I. viscosa, J. regia, P. lentiscus, Plumbago europea, Ruscus aculeatus, Retema raetam and Salvia fruticosa against T. violaceum. The MICs of these most active plants ranged from 0.6 to 40 micrograms ml-1. The three dermatophytes differed significantly with regard to their susceptibility to plant extracts. Trichophyton violaceum was the most susceptible being completely inhibited by 50% of the extracts followed by M. canis and T. mentagrophytes which were completely inhibited by only 23 and 14% of the extracts, respectively.

  Cyclic nucleotides and production of prostanoids in human varicose veins.:J Vasc Surg. 1999 Nov;30(5):876-83.Nemcova S, Gloviczki P, Rud KS, Miller VM. Division of Vascular Surgery, Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota, USA.

 OBJECTIVE: Experiments were designed to determine the production of prostacyclin and thromboxane and the activation of cyclic nucleotides in human varicose and nonvaricose veins and to determine whether these second messenger pathways were differentially activated by the venotropic extract of Ruscus aculeatus. METHODS: The experiments were designed to characterize the activity of cyclic nucleotides and the production of prostaglandins in human varicose and nonvaricose veins. Segments of the greater saphenous veins and the adjacent tributaries were obtained from patients who underwent vein stripping and excision of primary varicose veins. The saphenous veins from the patients who underwent peripheral arterial bypass grafting were used as controls. The segments of veins were incubated in Krebs-Ringer bicarbonate solution in the presence of venotropic extract of Ruscus aculeatus (10(-3) g/mL) or in water-miscible organic solvent (dimethyl sulfoxide, 10(-3) g/mL), for 1, 5, and 10 minutes at 37 degrees C. The nonspecific phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, 10(-4) g/mL) was used to block cyclic nucleotide degradation in some samples. Tissue and media samples were collected. Tissue concentrations of both cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP and cGMP, respectively) and media concentrations of 6-ketoprostaglandin-F(1)(alpha) (the stable metabolite of prostacyclin) and thromboxane B(2) (the stable metabolite of thromboxane A(2)) were measured by means of radioimmunoassay. Cyclooxygenase 2 was measured with Western blot analysis. RESULTS: The varicose veins showed greater levels of cAMP but not of cGMP at all time points as compared with the control veins. Prostanoid production was not significantly altered in the varicose veins. Stimulation with Ruscus aculeatus increased the cAMP concentration in the varicose veins but did not affect the cGMP levels. The ratio between 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was two-fold greater in the varicose veins as compared with the control veins. In the presence of the extract, the ratio of 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was identical in both types of veins. Cyclooxygenase 2 was not present in either the control or the varicose veins. CONCLUSION: These results suggest that cAMP levels are elevated in varicose veins and that they can be altered with drug treatment in varicose veins. This chemical pathway may be considered as a modulatory target to affect contraction with venotropic drugs.


  A spirostanol saponin from the underground parts of Ruscus aculeatus.:Phytochemistry. 1999 Jul;51(5):689-92.

 A new spirostanol saponin was isolated from the underground parts of Ruscus aculeatus and the structure was assigned as (23S,25R)-spirost-5-ene-3 beta,23-diol 23-O-[O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside] on the basis of spectroscopic analysis, including two-dimensional NMR spectroscopic techniques and the result of acid hydrolysis. The saponin is unique in structure having a diglycoside unit at C-23 of the spirostanol skeleton.

  Aculeoside B, a new bisdesmosidic spirostanol saponin from the underground parts of Ruscus aculeatus.:J Nat Prod. 1998 Oct;61(10):1279-82.

 From the underground parts of Ruscus aculeatus, a new bisdesmosidic spirostanol saponin named aculeosides B (2) was isolated, and its structure was determined on the basis of spectroscopic analysis, including 2D NMR techniques. Aculeoside A (1), which was previously isolated from the same plant source, exhibited inhibitory activity on cell growth of leukemia HL-60 cells with an IC50 value of 0.48 microgram mL(-1), while aculeoside B (2) was inactive.

  Steroidal saponins from the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells.:

 Phytochemical examination of the underground parts of Ruscus aculeatus has been undertaken as part of systematic study of plants of the Liliaceae. Six new spirostanol saponins and five new furostanol saponins were isolated, and their structures were assigned on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three acetyl groups attached to the inner galactosyl moiety and its corresponding 26-glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.

  New steroidal constituents of the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells.:Chem Pharm Bull. 1998 Feb;46(2):298-303.

 Phytochemical examination of the underground parts of Ruscus aculeatus has led to the isolation of a total of twelve steroidal saponins, including seven new ones. The structures of the new saponins were determined by spectroscopic analysis and chemical evidence. The furostanol saponin, having a diglycoside moiety modified with a (2S,3S)-2-hydroxy-3-methylpentanoic acid group and an acetic acid group, and its corresponding spirostanol saponin exhibited cytostatic activity on leukemia HL-60 cells.

  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). 1995 Oct;328(10):720-4.Facino RM, Carini M, Stefani R, Aldini G, Saibene L.Istituto Chimico Farmaceutico Tossicologico, Faculty of Pharmacy, University of Milan, Italy.

 Triterpene and steroid saponins and sapogenins of medicinal plants (Aesculus hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be effective for the treatment/prevention of venous insufficiency. In this work we evaluated the inhibitory effects of these plant constituents on the activity of elastase and hyaluronidase, the enzyme systems involved in the turnover of the main components of the perivascular amorphous substance. The results evidence that for Hedera helix L., the sapogenins only non-competitively inhibit hyaluronidase activity in a dose-dependent fashion, showing comparable IC50 values (hederagenin IC50 = 280.4 microM; oleanolic acid IC50 = 300.2 microM); both the saponins hederacoside C and alpha-hederin are very weak inhibitors. The same behaviour is observed for serine protease porcine pancreatic elastase: the glycosides are devoid of inhibitory action, while genins are potent competitive inhibitors (oleanolic acid IC50 = 5.1 microM; hederagenin IC50 = 40.6 microM). Constituents from Aesculus hippocastanum L. show inhibitory effects only on hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 = 149.9 microM), less to its genin escinol (IC50 = 1.65 mM). By contrast, ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity, exhibit remarkable anti-elastase activity (IC50 = 119.9 microM; competitive inhibition). The mechanism of elastase inhibition by triterpene and steroid aglycones, with a nitroanilide derivative as substrate, is discussed.


  Possible mechanisms for the inhibitory effect of Ruscus extract on increased microvascular permeability induced by histamine in hamster cheek pouch.:J Cardiovasc Pharmacol. 1994 Aug;24(2):281-5.Bouskela E, Cyrino FZ, Marcelon G.Department of Physiology and Biophysics, University of Lund, Sweden.

 Extract of Ruscus aculeatus is used in treatment of venous insufficiency. In the present study, we used the hamster cheek pouch preparation and investigated in vivo the effects of an alpha 1 and alpha 2 adrenoceptor antagonists, a calcium blocker, Ruscus extract, and their combination on increased microvascular permeability induced by histamine. Experiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran (molecular weight 150,000) was given intravenously (i.v.). Histamine, applied topically, increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence of an increase in macromolecular permeability, which was quantified by ultraviolet light microscopy as the number of leaky sites in the prepared area. Prazosin (alpha 1-adrenoceptor antagonist), diltiazem (calcium blocker), and Ruscus extract applied topically dose-dependently inhibited the macromolecular permeability-increasing effect of histamine. Rauwolscine (alpha 2-adrenoceptor antagonist), also applied topically, had no effect on histamine-induced permeability increase. Inhibition of the histamine-induced permeability increase evoked by Ruscus extract could be blocked by prazosin and by diltiazem but not by rauwolscine. These results indicate that any variation in the transmembrane flux of calcium impairs formation of microvascular leaky sites by histamine. Our results show that Ruscus extract has a protective effect against the leakage of FITC-dextran in hamster cheek pouch after administration of histamine that is modulated by calcium and selectively by alpha 1-adrenoceptors.

  Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation.:J Cardiovasc Pharmacol. 1993 Aug;22(2):221-4.Bouskela E, Cyrino FZ, Marcelon G.Department of Physiology and Biophysics, University of Lund, Sweden.

 In the present study, we investigated (a) the effects of the extract of Ruscus aculeatus, which is used to increase peripheral venous tone, on the diameter of arterioles (ID range 10-70 microns) and venules (ID range 20-135 microns) of hamster cheek pouch microvasculature in vivo and (b) the influence of temperature on the observed effects. For microcirculatory measurements, the preparations were placed under an intravital microscope and coupled to a closed-circuit TV (ccTV) system. The TV monitor display was used to obtain arteriolar and venular ID recordings (always at the same site) by an image shearing device. For systemic intravenous (i.v.) administration, the measurements were performed every 10 min, before (control) and after injection of the extract (5 mg/kg). During topical application, the extract was tested, in different concentrations, at 25 degrees, 36.5 degrees, and 40 degrees C. Systemic i.v. administration of Ruscus extract evoked venular constriction and did not affect the arteriolar diameter or mean arterial pressure (MAP). Topical application of Ruscus extract elicited concentration- and temperature-dependent responses in the vessels. At 25 degrees C, arterioles and venules dilated; at 36.5 degrees C, the arterioles remained unchanged while the venules constricted, and at 40 degrees C, the arterioles remained unchanged or constricted depending on the concentration used while the venules further constricted. The effects of Ruscus extract observed in vivo at the microcirculatory level further support the data previously reported on larger vessels and on patients with venous insufficiency.

  Use of extract of Ruscus aculeatus in venous disease in the lower limbs:Drugs Exp Clin Res. 1988;14(4):277-83.Cappelli R, Nicora M, Di Perri T.Institute of Medical Pathology, Unviersity of Siena, Italy.

 The effectiveness and tolerability of a venotropic drug (RAES) composed of an extract of Ruscus aculeatus (16.5 mg), hesperidin (75 mg) and ascorbic acid (50 mg) were evaluated in 40 patients (30 female, 10 male) aged between 28 and 74 years, suffering from chronic phlebopathy of the lower limbs. The cross-over, double-blind trial involved two periods of treatment of 2 months with the drug (2 capsules, 3 times/day) or with placebo, and an interim period of 15 days for wash-out. An overall tendency for improvement occurred that was more distinct during the periods of treatment with the drug. In fact, symptoms and plethysmographic parameters (in particular MVIV 40 and 60) immediately changed significantly in correspondence with the administration of RAES. The biological and clinical tolerability were excellent.

  Controlled study of increasing venous tone in primary varicose veins by oral administration of Ruscus aculeatus and trimethylhespiridinchalcone.:Z Hautkr. 1987 Jan 1;62(1):28-38. German.Weindorf N, Schultz-Ehrenburg U.

 In a randomized double blind study, 50 patients suffering from trunk or branch varicosis were orally treated with either a commercial preparation of Ruscus extract, trimethyl hesperidine chalcone and ascorbic acid (Phlebodril), or a placebo over 2 weeks. Changes of the venous tonus were measured by means of venous occlusion plethysmography in rest position (venous capacity, venous distensibility) as well as during (active) exercise (expelled blood volume). All parameters showed a tendency towards improvement in the verum group. The changes were partly significant (p less than 0.5). The course of the study suggests that the period of treatment possibly was too short to obtain the full pharmacologic effect.

  Effect of temperature on the responsiveness of cutaneous veins to the extract of Ruscus aculeatus.:Gen Pharmacol. 1984;15(5):431-4.Rubanyi G, Marcelon G, Vanhoutte PM.

 In canine cutaneous veins cooling augments and warming depresses the responses to sympathetic nerve stimulation. In these veins the extract of Ruscus aculeatus (Ruscus) causes contractions due to alpha-adrenergic activation. To determine the effects of temperature on the response to Ruscus, rings of canine saphenous veins were studied at 24 degrees, 37 degrees and 41 degrees C. At 37 degrees C, Ruscus caused an increase in isometric tension which was depressed by prazosin and rauwolscine. Cooling inhibited the response to Ruscus, while warming augmented it. Rauwolscine potentiated, and prazosin reversed the effect of cooling on contractions evoked by Ruscus. Prazosin reduced, and rauwolscine augmented the effect of warming. These experiments demonstrate that temperature affects the venoconstriction induced by Ruscus in an opposite fashion as that to sympathetic nerve activation, presumably because the alpha 1-adrenergic component of the response to Ruscus predominates.


  Quantitative determination of ruscogenin in Ruscus species by densitometric thin-layer chromatography.:Pharmazie. 1976;31(9):611-2.Nikolov S, Joneidi M, Panova D.

 A densitometric t.l.c. method of quantitative determination of ruscogenin was elaborated. After separation with the aid of t.l.c., the colourless ruscogenin spots were located with the aid of a p-dimethyl-aminobenzaldehyde solution and were submitted to densitometry. It was found that under the selected conditions a linear dependence exists between the betaI% value and lgC within the range of 0.5--10 mug ruscogenin. The determination of ruscogenin is done in the presence of the remaining components of the sample. The method is free of any systematic error. The method was applied in the determination of the ruscogenin content of the above-ground and underground part of Ruscus aculeatus and R. hypoglossum, extracts of the same plants, and capsules with further to the R. aculeatus extract also contained bioflavonoids. It was found that the content of ruscogenin in the underground and the above-ground parts of R. hypoglossum is 0.14 and 0.10%, respectively, while for R. aculeatus the respective values are 0.12 and 0.08%. The extract contains 1.6% ruscogenin, and the capsules 0.09 mg each.

  Constituents of Ruscus aculeatus.:Lloydia. 1975 Mar-Apr;38(2):106-8.ElSohly M, Knapp JE, Slatkin KF, Schiff PL Jr, Doorenbos NJ, Quimby MW.

 A phytochemical investigation of the acidic fraction from an ethanolic extract of the roots of Ruscus aculeatus L. (Liliaceae) has resulted in the isolation and identification of a sterol mixture, a fatty acid mixture, chrysophanic acid, a new compound named euparone and an incompletely characterized phenolic substance.


  Butcher's Broom Extract.VEGF Booster. Prompt hair growth.:

 Ruscus aculeatus Extracts can stimulate the production of VEGF(vascularendothelialgrowthfactor,VEGF), could be used to treat disease of hair, especially Alopecia areata and MPB(common baldness,male-pattern baldness, or permanent-pattern baldness). Otherwise, Ruscus aculeatus Extracts can be used combined with other herbs to boost VEGF and protect skin and anti-aging.
 Primarily used as an anti inflamatory upon the vascular system, easing venous circulation thru the body, especially the limbs. Effective for rheumatic, arthritic, and hemorrhoidal pains. Contains glycosides, neuruscogenins, puscogenins. and saponin.

  The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella asiatica, Ruscus aculeatus and Galphimia glauca cultured plants.:

 Considering that exogenously applied methyl jasmonate can enhance secondary metabolite production in a variety of plant species and that 2,3-oxidosqualene is a common precursor of triterpenes and sterols in plants, we have studied Centella asiatica and Galphimia glauca (both synthesizing triterpenoid secondary compounds) and Ruscus aculeatus (which synthesizes steroidal secondary compounds) for their growth rate and content of free sterols and respective secondary compounds, after culturing with or without 100muM methyl jasmonate. Our results show that elicited plantlets of G. glauca and to a higher degree C. asiatica (up to 152-times more) increased their content of triterpenoids directly synthesized from 2,3-oxidosqualene (ursane saponins and nor-seco-friedelane galphimines, respectively) at the same time as growth decreased. In contrast, the free sterol content of C. asiatica decreased notably, and remained practically unaltered in G. glauca. However, in the case of R. aculeatus, which synthesizes steroidal saponins (mainly spirostane type) indirectly from 2,3-oxidosqualene after the latter is converted to the plant phytosterol-precursor cycloartenol, while the growth rate and free sterol content clearly decreased, the spirostane saponine content was virtually unchanged (aerial part) or somewhat lower (roots) in presence of the same elicitor concentration. Our results suggest that while methyl jasmonate may be used as an inducer of enzymes involved in the triterpenoid synthesis downstream from 2,3-oxidosqualene in both C. asiatica and G. glauca plantlets, in those of C. asiatica and R. aculeatus it inhibited the enzymes involved in sterol synthesis downstream from cycloartenol.

  Effect of organogenesis on steroidal saponin biosynthesis in calli cultures of Ruscus aculeatus.:

 Calli cultures derived from Ruscus aculeatus rhizomes were investigated for their potential to biosynthesize saponins. The capacity of undifferentiated tissues to form steroidal saponins is very limited, but when the calli developed organogenesis, mainly aerial shoots and roots, the saponin production increased significantly. Plantlets regenerated from aerial shoots of Ruscus calli showed a saponin pattern similar to that of the callus cultures but the levels of saponins found in the aerial part and roots were significantly greater.

  Butcher's Broom, in the treatment of venous insufficiency.:
 Numerous extracts of the plants, natural compounds and their derivatives, acting on the venous system, including horse-chestnut seed extracts aescin, rutin, troxerutin, diosmin and hesperidine. They have a long tradition in herbal medicine for their venotonic and anti-oedematous properties. This review is concerning Rusci aculeati rhizoma, which recently taken in Poland on the symptoms of chronic venous insufficiency and hemorrhoids.

  Determination of anthocyanins in Ruscus aculeatus L. berries.:

 Red berries of Ruscus aculeatus L., a wild shrub typical of Mediterranean Europe and Africa, were investigated for the first time in order to determine the profile of anthocyanins. The pigments were extracted from the skins of the berries with 0.1% HCl in methanol, purified using a C-18 solid phase cartridge, and identified by means of high-performance liquid chromatography (HPLC)-diode array detection-mass spectrometry analysis. Information from HPLC profiles, saponification, and acid hydrolysis of the anthocyanins showed that the major anthocyanins were pelargonidin 3-O-rutinoside (64%), pelargonidin 3-O-glucoside (16%), and pelargonidin 3-O-trans-p-coumarylglucoside (13%). The attractive color of R. aculeatus berries and the great abundance of the plant in the south of Italy make these berries a new and promising source of natural colorants.

  Inhibition of COX isoforms by nutraceuticals.:

 Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase: COX-1 and COX-2. COX-1 is cytoprotective. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage. The ideal nutraceutical would inhibit COX-2 synthesis while preserving COX-1 synthesis. The hypothesis for this research was that COX inhibitors would fall primarily into three categories: COX-2 specific inhibition, non-specific inhibition (COX-1 and COX-2), and minimal inhibition. The human Cayman COX inhibitor screening assay was used to determine the inhibitory concentration 50 (IC50) of COX-1/ COX-2 activity of each nutraceutical. The assay was run, in duplicate, with three concentrations of a suspected inhibitor, a standard curve of eight concentrations, a non-specific binding sample, and a maximum binding sample. The inhibition and concentration of each sample was then put on a multiple regression best-fit line and the IC50 determined. For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used. Positive results were seen for ipriflavone, resveratrol, MSV-60, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform.


  Identification of Ruscus steroidal saponins by HPLC-MS analysis.:

 A novel HPLC-UV method has been developed for the fingerprint analysis of the steroidal saponins in the rhizomes of three Ruscus species (Ruscus aculeatus, Ruscus hypoglossum and Ruscus colchicus). Saponins were identified by HPLC-ESI-MS. During the study a new major saponin was detected in the rhizomes of R. hypoglossum and R. colchicus. The structure of the new compound was defined as 1-O-[alpha-L-rhamnopyranosyl-(1-->2)-6-O-acetyl-beta-D-galactopyranosyl]-1beta,3beta,22xi,26-tetrahydroxy-furost-5(6)-en-26-O-beta-D-glucopyranoside (8) by spectral analysis.

  Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency.:

 Extracts from Butcher's broom rhizome (Ruscus aculeatus) have been widely used in the oral treatment of lower leg edema in patients with chronic venous insufficiency. The aim of the present multi-center, double-blind, randomized, placebo-controlled trial was to confirm the efficacy and safety of a ruscus extract (Fagorutin Ruscus Kapseln) according to the latest scientific standards. 166 women suffering from chronic venous insufficiency (Widmer grade I and II, CEAP (Clinical signs, Etiological classification, Anatomic distribution, Pathophysiology) 3-4) were included. The data of 148 patients (30-89 years, 150-182 cm height, 49-97 kg body weight) with a mean disease duration of 14.6 years in the ruscus extract group and 15.1 years in the placebo group were eligible for the intent-to-treat-analysis. The primary parameter was the area under baseline of the leg volume changes over 12 weeks (AUB0-12). Secondary parameters were the changes in circumference of the lower leg and the ankle, changes in subjective symptoms and quality of life, the overall efficacy and tolerability and safety parameters. The study was carried out according to the guidelines for testing drugs for chronic venous insufficiency. There were significant differences between the treatment groups ruscus and placebo for the AUB0-12 (-827 ml x day), for the change of leg volume after 8 and 12 weeks of treatment (-16.5 ml and -20.5 ml), for changes in ankle and leg circumferences after 8 and 12 weeks of treatment, and for the changes in subjective symptoms, heavy tired legs and sensation of tension (week 12). For the changes in the symptoms heavy lower legs, sensation of tension, and tingling sensation a significant positive correlation with the changes in leg volume was shown. Overall assessment of efficacy was significantly better for ruscus extract compared to placebo. Overall tolerability for both treatments was assessed as good and very good. Of all 48 adverse events occurring in both treatment groups, 22 were reported in the ruscus group, one of them was considered to be related to the study medication (unlikely). Considering the study duration of three months it is concluded, that ruscus extract, in the recommended daily dosage according to the German monograph, is a safe and effective treatment for patients suffering from chronic venous insufficiency.


  Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report.:

 CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects large groups of the population with autonomic insufficiency--the elderly; patients with diabetes, Parkinson's disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders. OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy for OH and encourage further studies on the efficacy of Ruscus for OH patients. DESIGN: Review of OH and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its mechanism of action, and its suitability as a therapeutic agent for treatment of OH. RESULTS: A review of the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other therapy can offer--alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an extremely safe, inexpensive, over-the-counter botanical medicine. CONCLUSION: With proven phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus shows great promise for ameliorating the symptoms of OH and improving the quality of life for large groups in the population. It clearly deserves to be the object of wider research and study as a treatment for OH.
 


  Traditional phytotherapy in Central Italy (Marche, Abruzzo, and Latium).:

 In this study, the more significant results of extensive ethnopharmacobotanical research carried out by the author in the years 1977-2000 in 175 localities of three regions of Central Italy (Marche, Abruzzo, and Latium) have been reported and compared. The usages of 80 species belonging to 36 families are described, of which 71 were used in human therapy and 29 in veterinary medicine. Uses are suited with the number of localities in which they have been mentioned. Among the wild plant mainly still used, Malva sylvestris, Urtica dioica, and Sambucus nigra are particularly highly considered, while major uses of plants concern these plants in addition to Allium sativum, Rubus ulmifolius, Parietaria diffusa, Cynodon dactylon, and Ficus carica. Unusual phytotherapic uses concern Brassica oleracea, Taraxacum officinale (warts), Ruscus aculeatus, S. nigra (chilblains), Allium cepa (chilblains; to remove thorns and splinters), Juglans regia, R. ulmifolius (burns), and Euphorbia paralias (bites of weevers). Among new uses with only one quotation, we remember Cirsium arvense (intestinal disturbances), Centaurea bracteata (cough), Lupinus albus (calluses), Melittis melissophyllum (eye inflammations, antispasmodic), and Artemisia absinthium (tendon inflammations), while among plants employed in various regions with interesting less-known properties, there are C. arvense (emergency haemostatic), P. diffusa (insect bites), and Scrophularia canina (antiseptic and cicatrizing agent for wounds in bovines and sheep).

  Hemorrhoids and varicose veins: a review of treatment options.:

 Hemorrhoids and varicose veins are common conditions seen by general practitioners. Both conditions have several treatment modalities for the physician to choose from. Varicose veins are treated with mechanical compression stockings. There are several over-the-counter topical agents available for hemorrhoids. Conservative therapies for both conditions include diet, lifestyle changes, and hydrotherapy which require a high degree of patient compliance to be effective. When conservative hemorrhoid therapy is ineffective, many physicians may choose other non-surgical modalities: injection sclerotherapy, cryotherapy, manual dilation of the anus, infrared photocoagulation, bipolar diathermy, direct current electrocoagulation, or rubber band ligation. Injection sclerotherapy is the non-surgical treatment for primary varicose veins. Non-surgical modalities require physicians to be specially trained, own specialized equipment, and assume associated risks. If a non-surgical approach fails, the patient is often referred to a surgeon. The costly and uncomfortable nature of treatment options often lead a patient to postpone evaluation until aggressive intervention is necessary. Oral dietary supplementation is an attractive addition to the traditional treatment of hemorrhoids and varicose veins. The loss of vascular integrity is associated with the pathogenesis of both hemorrhoids and varicose veins. Several botanical extracts have been shown to improve microcirculation, capillary flow, and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation with Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, Hamamelis virginiana, and bioflavonoids may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids.


  Pharmacological assessment of adrenergic receptors in human varicose veins.:

 BACKGROUND: Experiments were to characterize pharmacologically adrenergic receptors in human varicose veins to the natural transmitter norepinephrine and to an extract of Ruscus. METHODS: Greater saphenous veins and varicose tributaries from patients undergoing elective surgery for primary varicose disease and portions of greater saphenous veins from patients undergoing peripheral arterial reconstruction (control) were suspended for the measurement of isometric force in organ chambers. Concentration response curves were obtained to norepinephrine or the extract of Ruscus aculeatus in the absence and presence of selective antagonists of alpha, and alpha2 adrenergic receptors. RESULTS: Norepinephrine and Ruscus extract caused concentration-dependent contractions in all veins. Contractions to norepinephrine were greater in control veins than in varicose tributaries. Contractions to the extract were greater in varicose tributaries than in greater saphenous veins from varicose patients. Contractions to norepinephrine were reduced similarly by alpha and alpha2-adrenergic agonists in control and varicose veins but to a greater extent by alpha2-blockade in greater saphenous veins from varicose patients. Contractions to Ruscus extract were not reduced by alpha-adrenergic blockade in control veins but were reduced by alpha2-adrenergic blockade in varicose veins. CONCLUSIONS: These results suggest a differential distribution of alpha adrenergic receptors on greater saphenous veins from non-varicose patients compared to those with primary varicose disease. Venotropic agents from plant extract probably exert effects by way of multiple receptor and non-receptor mediated events.

  Effect of Ruscus extract and hesperidin methylchalcone on hypoxia-induced activation of endothelial cells.:

 BACKGROUND: Ruscus aculeatus extract and the flavonoid hesperidin methylchalcone (HMC) are drugs used in the treatment of chronic venous insufficiency. METHODS: In the present study, we investigated their effects on the activation of endothelial cells by hypoxia, a condition which mimics venous blood stasis. RESULTS: We observed that Ruscus extract was able to inhibit the activation of endothelial cells by hypoxia: the decrease in ATP content, the activation of phospholipase A2 as well as the subsequent increase in neutrophil adherence with a maximal protection obtained at 50 microg/ml. HMC was also able to inhibit the hypoxia-induced decrease in ATP content. Furthermore, the effects of Ruscus extract and of HMC on this decrease seem to be additive. CONCLUSIONS: The biochemical mechanism evidenced in this work might explain some of the beneficial therapeutic effects of these products in the treatment of chronic venous insufficiency patients.

  Antifungal activity of plant extracts against dermatophytes.:

 The aqueous extracts (15 micrograms ml-1 medium) of 22 plants used in folkloric medicine in Palestine were investigated for their antifungal activity and minimum inhibitory concentrations (MICs) against nine isolates of Microsporum canis, Trichophyton mentagrophytes and Trichophyton violaceum. The extract of the different plant species reduced colony growth of the three dermatophytes by 36 to 100% compared with the control treatment. Antimycotic activity of the extract against the three dermatophytes varied significantly (P < 0.05) between test plants. Extracts of Capparis spinosa and Juglans regia completely prevented growth of M. canis and T. violaceum. The most active extracts (90-100% inhibition) were those of Anagallis arvensis, C. spinosa, J. regia, Pistacia lentiscus and Ruta chalapensis against M. canis; Inula viscosa, J. regia and P. lentiscus against T. mentagrophytes; and Asphodelus luteus, A. arvensis, C. spinosa, Clematis cirrhosa, I. viscosa, J. regia, P. lentiscus, Plumbago europea, Ruscus aculeatus, Retema raetam and Salvia fruticosa against T. violaceum. The MICs of these most active plants ranged from 0.6 to 40 micrograms ml-1. The three dermatophytes differed significantly with regard to their susceptibility to plant extracts. Trichophyton violaceum was the most susceptible being completely inhibited by 50% of the extracts followed by M. canis and T. mentagrophytes which were completely inhibited by only 23 and 14% of the extracts, respectively.


  Cyclic nucleotides and production of prostanoids in human varicose veins.:

 OBJECTIVE: Experiments were designed to determine the production of prostacyclin and thromboxane and the activation of cyclic nucleotides in human varicose and nonvaricose veins and to determine whether these second messenger pathways were differentially activated by the venotropic extract of Ruscus aculeatus. METHODS: The experiments were designed to characterize the activity of cyclic nucleotides and the production of prostaglandins in human varicose and nonvaricose veins. Segments of the greater saphenous veins and the adjacent tributaries were obtained from patients who underwent vein stripping and excision of primary varicose veins. The saphenous veins from the patients who underwent peripheral arterial bypass grafting were used as controls. The segments of veins were incubated in Krebs-Ringer bicarbonate solution in the presence of venotropic extract of Ruscus aculeatus (10(-3) g/mL) or in water-miscible organic solvent (dimethyl sulfoxide, 10(-3) g/mL), for 1, 5, and 10 minutes at 37 degrees C. The nonspecific phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, 10(-4) g/mL) was used to block cyclic nucleotide degradation in some samples. Tissue and media samples were collected. Tissue concentrations of both cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP and cGMP, respectively) and media concentrations of 6-ketoprostaglandin-F(1)(alpha) (the stable metabolite of prostacyclin) and thromboxane B(2) (the stable metabolite of thromboxane A(2)) were measured by means of radioimmunoassay. Cyclooxygenase 2 was measured with Western blot analysis. RESULTS: The varicose veins showed greater levels of cAMP but not of cGMP at all time points as compared with the control veins. Prostanoid production was not significantly altered in the varicose veins. Stimulation with Ruscus aculeatus increased the cAMP concentration in the varicose veins but did not affect the cGMP levels. The ratio between 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was two-fold greater in the varicose veins as compared with the control veins. In the presence of the extract, the ratio of 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was identical in both types of veins. Cyclooxygenase 2 was not present in either the control or the varicose veins. CONCLUSION: These results suggest that cAMP levels are elevated in varicose veins and that they can be altered with drug treatment in varicose veins. This chemical pathway may be considered as a modulatory target to affect contraction with venotropic drugs.


  A spirostanol saponin from the underground parts of Ruscus aculeatus.:

 A new spirostanol saponin was isolated from the underground parts of Ruscus aculeatus and the structure was assigned as (23S,25R)-spirost-5-ene-3 beta,23-diol 23-O-[O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside] on the basis of spectroscopic analysis, including two-dimensional NMR spectroscopic techniques and the result of acid hydrolysis. The saponin is unique in structure having a diglycoside unit at C-23 of the spirostanol skeleton.

  Aculeoside B, a new bisdesmosidic spirostanol saponin from the underground parts of Ruscus aculeatus.:

 From the underground parts of Ruscus aculeatus, a new bisdesmosidic spirostanol saponin named aculeosides B (2) was isolated, and its structure was determined on the basis of spectroscopic analysis, including 2D NMR techniques. Aculeoside A (1), which was previously isolated from the same plant source, exhibited inhibitory activity on cell growth of leukemia HL-60 cells with an IC50 value of 0.48 microgram mL(-1), while aculeoside B (2) was inactive.

  Steroidal saponins from the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells.:

 Phytochemical examination of the underground parts of Ruscus aculeatus has been undertaken as part of systematic study of plants of the Liliaceae. Six new spirostanol saponins and five new furostanol saponins were isolated, and their structures were assigned on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three acetyl groups attached to the inner galactosyl moiety and its corresponding 26-glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.

  Antipermeability effects of Cyclo 3 Fort in hamsters with moderate diabetes.:

 Ruscus aculeatus extract (the active principle of Cyclo 3 Fort) is used to increase venous tone in patients with venous disease. In these experiments, the effects of oral Cyclo 3 Fort on capillary permeability were studied in hamsters with moderate diabetes induced by two intraperitoneal injections of streptozotocin (40 mg/kg). Hamsters were treated with a placebo or Cyclo 3 Fort, 2, 10 or 50 mg/kg/day, for 4 weeks starting 3 days after induction of diabetes. Intravital microscopy of cheek pouch preparations was performed using fluorescein-labelled dextran (FITC-dextran) as a marker for plasma exudation (leak formation). Plasma levels of glucose were measured prior to experiments. Following preparation for intravital microscopy, each cheek pouch was subjected to two applications of histamine, 5 x 10(-6) M for 5 min at 30-minute intervals. Plasma exudation (number of leaks/cm2) was significantly reduced in animals receiving Cyclo 3 Fort at doses of 10 mg/kg or above. The mean number of leaks was 258 +/- 17 in the placebo group, compared with 253 +/- 12, 125 +/- 7 (p < 0.01) and 99 +/- 7 (p < 0.01) in animals receiving Cyclo 3 Fort, 2, 10 or 50 mg/kg, respectively. Blood glucose levels did not differ between groups. Thus, oral Cyclo 3 Fort inhibited histamine-induced plasma exudation in hamsters with mild diabetes without affecting the glycaemia.


  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.:

 Triterpene and steroid saponins and sapogenins of medicinal plants (Aesculus hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be effective for the treatment/prevention of venous insufficiency. In this work we evaluated the inhibitory effects of these plant constituents on the activity of elastase and hyaluronidase, the enzyme systems involved in the turnover of the main components of the perivascular amorphous substance. The results evidence that for Hedera helix L., the sapogenins only non-competitively inhibit hyaluronidase activity in a dose-dependent fashion, showing comparable IC50 values (hederagenin IC50 = 280.4 microM; oleanolic acid IC50 = 300.2 microM); both the saponins hederacoside C and alpha-hederin are very weak inhibitors. The same behaviour is observed for serine protease porcine pancreatic elastase: the glycosides are devoid of inhibitory action, while genins are potent competitive inhibitors (oleanolic acid IC50 = 5.1 microM; hederagenin IC50 = 40.6 microM). Constituents from Aesculus hippocastanum L. show inhibitory effects only on hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 = 149.9 microM), less to its genin escinol (IC50 = 1.65 mM). By contrast, ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity, exhibit remarkable anti-elastase activity (IC50 = 119.9 microM; competitive inhibition). The mechanism of elastase inhibition by triterpene and steroid aglycones, with a nitroanilide derivative as substrate, is discussed.

  Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation.:

 In the present study, we investigated (a) the effects of the extract of Ruscus aculeatus, which is used to increase peripheral venous tone, on the diameter of arterioles (ID range 10-70 microns) and venules (ID range 20-135 microns) of hamster cheek pouch microvasculature in vivo and (b) the influence of temperature on the observed effects. For microcirculatory measurements, the preparations were placed under an intravital microscope and coupled to a closed-circuit TV (ccTV) system. The TV monitor display was used to obtain arteriolar and venular ID recordings (always at the same site) by an image shearing device. For systemic intravenous (i.v.) administration, the measurements were performed every 10 min, before (control) and after injection of the extract (5 mg/kg). During topical application, the extract was tested, in different concentrations, at 25 degrees, 36.5 degrees, and 40 degrees C. Systemic i.v. administration of Ruscus extract evoked venular constriction and did not affect the arteriolar diameter or mean arterial pressure (MAP). Topical application of Ruscus extract elicited concentration- and temperature-dependent responses in the vessels. At 25 degrees C, arterioles and venules dilated; at 36.5 degrees C, the arterioles remained unchanged while the venules constricted, and at 40 degrees C, the arterioles remained unchanged or constricted depending on the concentration used while the venules further constricted. The effects of Ruscus extract observed in vivo at the microcirculatory level further support the data previously reported on larger vessels and on patients with venous insufficiency.


  Use of extract of Ruscus aculeatus in venous disease in the lower limbs.:

 The effectiveness and tolerability of a venotropic drug (RAES) composed of an extract of Ruscus aculeatus (16.5 mg), hesperidin (75 mg) and ascorbic acid (50 mg) were evaluated in 40 patients (30 female, 10 male) aged between 28 and 74 years, suffering from chronic phlebopathy of the lower limbs. The cross-over, double-blind trial involved two periods of treatment of 2 months with the drug (2 capsules, 3 times/day) or with placebo, and an interim period of 15 days for wash-out. An overall tendency for improvement occurred that was more distinct during the periods of treatment with the drug. In fact, symptoms and plethysmographic parameters (in particular MVIV 40 and 60) immediately changed significantly in correspondence with the administration of RAES. The biological and clinical tolerability were excellent.

  Controlled study of increasing venous tone in primary varicose veins by oral administration of Ruscus aculeatus and trimethylhespiridinchalcone.:

 In a randomized double blind study, 50 patients suffering from trunk or branch varicosis were orally treated with either a commercial preparation of Ruscus extract, trimethyl hesperidine chalcone and ascorbic acid (Phlebodril), or a placebo over 2 weeks. Changes of the venous tonus were measured by means of venous occlusion plethysmography in rest position (venous capacity, venous distensibility) as well as during (active) exercise (expelled blood volume). All parameters showed a tendency towards improvement in the verum group. The changes were partly significant (p less than 0.5). The course of the study suggests that the period of treatment possibly was too short to obtain the full pharmacologic effect.

  Effect of temperature on the responsiveness of cutaneous veins to the extract of Ruscus aculeatus.:

 In canine cutaneous veins cooling augments and warming depresses the responses to sympathetic nerve stimulation. In these veins the extract of Ruscus aculeatus (Ruscus) causes contractions due to alpha-adrenergic activation. To determine the effects of temperature on the response to Ruscus, rings of canine saphenous veins were studied at 24 degrees, 37 degrees and 41 degrees C. At 37 degrees C, Ruscus caused an increase in isometric tension which was depressed by prazosin and rauwolscine. Cooling inhibited the response to Ruscus, while warming augmented it. Rauwolscine potentiated, and prazosin reversed the effect of cooling on contractions evoked by Ruscus. Prazosin reduced, and rauwolscine augmented the effect of warming. These experiments demonstrate that temperature affects the venoconstriction induced by Ruscus in an opposite fashion as that to sympathetic nerve activation, presumably because the alpha 1-adrenergic component of the response to Ruscus predominates.

  Quantitative determination of ruscogenin in Ruscus species by densitometric thin-layer chromatography.:

 A densitometric t.l.c. method of quantitative determination of ruscogenin was elaborated. After separation with the aid of t.l.c., the colourless ruscogenin spots were located with the aid of a p-dimethyl-aminobenzaldehyde solution and were submitted to densitometry. It was found that under the selected conditions a linear dependence exists between the betaI% value and lgC within the range of 0.5--10 mug ruscogenin. The determination of ruscogenin is done in the presence of the remaining components of the sample. The method is free of any systematic error. The method was applied in the determination of the ruscogenin content of the above-ground and underground part of Ruscus aculeatus and R. hypoglossum, extracts of the same plants, and capsules with further to the R. aculeatus extract also contained bioflavonoids. It was found that the content of ruscogenin in the underground and the above-ground parts of R. hypoglossum is 0.14 and 0.10%, respectively, while for R. aculeatus the respective values are 0.12 and 0.08%. The extract contains 1.6% ruscogenin, and the capsules 0.09 mg each.

  Constituents of Ruscus aculeatus.:

 A phytochemical investigation of the acidic fraction from an ethanolic extract of the roots of Ruscus aculeatus L. (Liliaceae) has resulted in the isolation and identification of a sterol mixture, a fatty acid mixture, chrysophanic acid, a new compound named euparone and an incompletely characterized phenolic substance.


  Scientific References:

  1.Research Update:Butcher's Broom or Ruscus aculeatus.