€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DRUGS UNDER EXPERIMENTAL AND CLINICAL RESEARCH***** Cappelli R Nicora M Di Perri T Use of extract of Ruscus aculeatus in venous disease in the lower limbs. In: Drugs Exp Clin Res (1988) 14(4):277-83 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FORTSCHRITTE DER MEDIZIN***** Berg D [Venous constriction by local administration of ruscus extract] Venenkonstriktion durch lokale Anwendung von Ruscusextrakt. In: Fortschr Med (1990 Aug 20) 108(24):473-6 (Published in German) The venoconstrictive action of the topical application of Ruscus extract was evaluated in a randomized, double-blind study involving 18 healthy volunteers, using duplex B-scan ultrasonography. Within 2 1/2 hours of the application of 4 to 6 g of a cream containing 64 to 96 mg Ruscus extract, the diameter of the femoral vein decreased by an average (median) of 1.25 mm, while placebo (base of the cream) was associated with a diameter increase of 0.5 mm (means) (p = 0.014). The decrease in venous diameter reflects good percutaneous absorption of the active substance. To date, venoconstrictive action has been demonstrable only indirectly with the aid of plethysmographic methods; it has now been measured directly under orthostatic conditions. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FORTSCHRITTE DER MEDIZIN***** Rudofsky G [Improving venous tone and capillary sealing. Effect of a combination of Ruscus extract and hesperidine methyl chalcone in healthy probands in heat stress] Venentonisierung und Kapillarabdichtung. Die Wirkung der Kombination aus Ruscus-Extrakt und Trimethylhesperidinchalkon bei gesunden Probanden unter Warmebelastung. In: Fortschr Med (1989 Jun 30) 107(19):52, 55-8 (Published in German) The drug combination of Ruscus-extract and hesperidine methyl chalcone (HMC) involves two basic mechanisms in the treatment of venous diseases: increase in venous tonicity and edema protection. This was shown in a double-blind study on 20 healthy volunteers by comparing the effectiveness of the individual substances, the combination and a placebo on the venous hemodynamics and the volume of the foot. Ruscus-extract augments the tonicity of the venous wall. This is expressed by a decrease in venous capacity (p less than 0.01), a reduction in the blood pool in the lower leg under orthostatic conditions, and a decrease in tissue volume of the foot and ankle (p less than 0.01). HMC lowers the capillary filtration rate (p less than 0.01) but augmented the blood pool. The increase in blood volume can be explained by dehydration of the tissue of the lower leg lowering the pressure of tissue on the venous system and increasing the blood pool in the limb. After administration of the combination, the blood volume was between the Ruscus and HMC volumes, while the effects on filtration rate, venous capacity and tissue volume corresponded to the changes seen after administration of HMC and Ruscus extract alone. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****GENERAL PHARMACOLOGY***** Rubanyi G Marcelon G Vanhoutte PM Effect of temperature on the responsiveness of cutaneous veins to the extract of Ruscus aculeatus. In: Gen Pharmacol (1984) 15(5):431-4 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CARDIOVASCULAR PHARMACOLOGY***** Bouskela E Cyrino FZ Marcelon G Possible mechanisms for the inhibitory effect of Ruscus extract on increased microvascular permeability induced by histamine in hamster cheek pouch. In: J Cardiovasc Pharmacol (1994 Aug) 24(2):281-5 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CARDIOVASCULAR PHARMACOLOGY***** Bouskela E Cyrino FZ Marcelon G Possible mechanisms for the venular constriction elicited by Ruscus extract on hamster cheek pouch. In: J Cardiovasc Pharmacol (1994 Jul) 24(1):165-70 We investigated the influence of alpha-adrenoceptors blockers and calcium blockers on the effects of the venotonic agent Ruscus extract on the diameter of arterioles (ID 10-70 microns) and venules (ID 20- 135 microns) of hamster cheek pouch microvasculature in vivo. For microcirculatory measurements, the preparations were placed under an intravital microscope coupled to a closed-circuit TV system. The TV monitor display was used to obtain arteriolar and venular internal diameter recordings (always at the same site) by an image shearing device. All drugs were applied topically. Ruscus extract was tested in different concentrations and in combination with prazosin (alpha 1- adrenoceptor antagonist), rauwolscine (alpha 2-adrenoceptor antagonist), or diltiazem (calcium blocker). Topical application of Ruscus extract elicited concentration-dependent responses in the studied vessels: arterioles remained unchanged in the concentration range tested, whereas venules remained unchanged or constricted depending on the concentration used. The observed venular constriction could be blocked by low concentrations (10(-9) M) of prazosin or diltiazem and by high concentrations (> 10(-6) M) of rauwolscine. Our results suggest that the venular constriction elicited by Ruscus extract in vivo, at the microcirculatory level, is mediated by calcium and by alpha-adrenoceptors and further support data previously reported on larger vessels and on patients with venous insufficiency. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CARDIOVASCULAR PHARMACOLOGY***** Bouskela E Cyrino FZ Marcelon G Inhibitory effect of the Ruscus extract and of the flavonoid hesperidine methylchalcone on increased microvascular permeability induced by various agents in the hamster cheek pouch. In: J Cardiovasc Pharmacol (1993 Aug) 22(2):225-30 The Ruscus extract and the flavonoid hesperidine methylchalcone (HMC) are used in treatment of venous insufficiency. In the present study, we used the hamster cheek pouch preparation and investigated the effects of these substances on increased microvascular permeability induced by bradykinin, histamine, and leukotriene B4 (LTB4) applied topically. Experiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran [molecular weight (mol wt) 150,000] was given intravenously (i.v.). Bradykinin, histamine, and LTB4 increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence for an increase in macromolecular permeability, which was quantified in ultraviolet (UV)-light microscope as the number of leaky sites in the prepared area. Ruscus extract and HMC, given i.v., significantly inhibited the macromolecular permeability-increasing effect of bradykinin, LTB4, and histamine. Ruscus extract, applied topically, dose dependently inhibited the macromolecular permeability- increasing effect of histamine. Our results show that Ruscus extract and HMC have a protective effect against leakage of FITC-dextran in the cheek pouch after administration of various permeability- increasing substances, which further supports data previously reported on patients with venous insufficiency. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CARDIOVASCULAR PHARMACOLOGY***** Bouskela E Cyrino FZ Marcelon G Effects of Ruscus extract on the internal diameter of arterioles and venules of the hamster cheek pouch microcirculation. In: J Cardiovasc Pharmacol (1993 Aug) 22(2):221-4 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LLOYDIA***** ElSohly M Knapp JE Slatkin KF Schiff PL Jr Doorenbos NJ Quimby MW Constituents of Ruscus aculeatus. In: Lloydia (1975 Mar-Apr) 38(2):106-8 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMAZIE***** Nikolov S Joneidi M Panova D Quantitative determination of ruscogenin in Ruscus species by densitometric thin-layer chromatography. In: Pharmazie (1976) 31(9):611-2 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ZEITSCHRIFT FUR HAUTKRANKHEITEN***** Weindorf N Schultz-Ehrenburg U [Controlled study of increasing venous tone in primary varicose veins by oral administration of Ruscus aculeatus and trimethylhespiridinchalcone] Kontrollierte Studie zur oralen Venentonisierung der primaren Varikosis mit Ruscus aculeatus und Trimethylhesperidinchalkon. In: Z Hautkr (1987 Jan 1) 62(1):28-38 (Published in German) 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€