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At least 127 records · Page 7Linked to original sources
PubMed2003

Flavonoid treatment in patients with healed venous ulcer: flow cytometry analysis suggests increased CD11b expression on neutrophil granulocytes in the circulation.

The objective was to determine the activation of white blood cells (WBCs) and endothelial cells in patients with healed venous ulcer and the influence of the standing position and of treatment with flavonoids. Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days. Blood samples were taken from arm and dorsal foot veins before and after standing for 30 minutes. Blood sampling was performed before treatment, after three days, one month and three months. The activation of WBCs was determined by measuring adhesion molecule CD11b and CD18 expression on the surface of granulocytes and monocytes. In addition, interleukin 6 (IL-6), IL-8, soluble E-selectin (sE-selectin), sL-selectin and sICAM-1 levels in serum were quantified. The results showed that standing did not influence any of the measured parameters significantly. Expression of CD11b adhesion molecules on granulocytes was significantly up-regulated (p = 0.044) after treatment with flavonoids for one month, but this increase was not significant (p = 0.056) two months after the treatment period compared with the baseline level. The expression of CD18 remained unchanged. Baseline expression of CD11b or CD18 on monocytes did not change significantly during the study period. Neither was any significant change observed in the levels of IL-6, IL-8 or the soluble adhesion molecules. It was concluded that flavonoid treatment for 30 days increased the expression of CD11b adhesion molecules on circulating granulocytes. No general effect on the inflammatory process could be observed as assessed by levels of cytokines and soluble adhesion molecules. Possible explanations for these findings could be that a decreased number of primed granulocytes leave the circulation due to a changed WBC/endothelial cell interaction or that flavonoids have a direct effect on granulocytes. Further studies are needed to clarify the mode of action of flavonoids in chronic venous disease.

Adult↗
PubMed2005

Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular uptake and hydrolysis to the aglycones.

Epidemiologic evidence supports the view that dietary flavonoids exert protective effects in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, are thought to be inactive, thus they must first be hydrolysed to their active aglycones. This may occur in the saliva in the oral cavity. We have examined if the flavonoid glycosides directly could affect cell proliferation, using the human oral squamous carcinoma SCC-9 cells. The cellular uptake and hydrolysis of the glycosides were assessed also. The four flavonoid glycosides tested each behaved differently. Genistin, the 7-glucoside of genistein, showed clear and consistent inhibition of cell proliferation, which appeared to be the result of rapid cellular uptake of the glucoside and hydrolysis to genistein. Spiraeoside, the 4'-glucoside of quercetin, showed a similar inhibition of cell proliferation, which also appeared to be associated with its hydrolysis to quercetin. Diosmin, the 7-rutinoside of diosmetin, surprisingly, was more potent and effective than diosmetin. In contrast, quercitrin, the 3-rhamnoside of quercetin, showed no effect and only minimal cellular uptake and no hydrolysis. In summary, dietary flavonoid glycosides may exert cellular effects in the oral cavity, but this varies greatly with the nature of the glycoside.

Carcinoma, Squamous Cell↗
PubMed2000

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology].

PURPOSE: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts. RESULTS: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes. CONCLUSION: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

Adenocarcinoma↗
PubMed1999

The effect of flavonoid treatment on the glycation and antioxidant status in Type 1 diabetic patients.

Amongst the numerous co-adjuvant therapies which could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in several clinical trials. In this study we investigated the effects of Daflon 500, which is made up of the flavonoids diosmin (90%) and hesperidin (10%), in a group of 28 Type 1 diabetic patients in a double blind placebo-controlled study. Parameters of glycation and oxidative stress were measured before and after the intervention. Treatment with this flavonoid had no side effects and was followed by a decrease in HbA1c, from 8.85+/-1.57 to 8.47+/-1.40% (p=0.017). This decrease was more pronounced in the patients with higher initial HbA1c but was unrelated to glycaemic control as monitored by the mean and fluctuations of daily glycaemia. Decrease in HbA1c was accompanied by an increase in glutathione peroxidase activity, from 119+/-68 to 145+/-42 U/l haemolysate (p=0.015), a tendency for increase in plasma protein thiols and an increase in the lag time of the copper-induced in vitro oxidability of non-HDL lipoproteins, from 96+/-24 to 111+/-28 min (p=0.005). These parameters did not change significantly after receiving placebo. Other parameters of antioxidant capacity such as blood GSH, catalase and superoxide dismutase activities, as well as in vitro formation of thiobarbituric acid reactive substances (TBARS), were unaffected by either flavonoid or placebo. Our results suggest that the flavonoid-induced decrease in glycation is associated with an increase in the antioxidant component dependent on the levels and activities of thiol-containing proteins such as glutathione peroxidase. One mechanism which could explain these effects is the protection of vitamin C and E from consumption by oxidative processes.

Adolescent↗
PubMedDate not supplied

Effects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.

NNK is a potent environmental carcinogen to which both smokers and nonsmokers are exposed. The response to NNK may be affected by factors including nutrition. We investigated the effects of five citrus phytochemicals on the in vitro metabolism of the tobacco-specific nitrosamine NNK and on the dealkylation of methoxyresorufin (MROD) and pentoxyresorufin (PROD) in liver and lung microsomes of the Syrian golden hamster. In the NNK metabolism experiments in vitro incubations contained 3 microCi [5-H3] NNK, 0.5 mg microsomal protein and 0.5 mumole of the citrus phytochemical diosmin, naringin, naringenin, quercetin or rutin. In the dealkylation studies incubations contained 0.5 microM methoxyresorufin or pentoxyresorufin, 0.5 mg microsomal protein and 0.5 mumole of citrus phytochemical. The major NNK metabolism pathway in hamster liver microsomes was NNK-reduction while in lung microsomes it was alpha-hydroxylation. The alpha-hydroxylation pathway produces metabolic products that methylate and pyridyloxobutylate DNA. Naringenin, a metabolite of naringin, and quercetin were the most potent inhibitors of alpha-hydroxylation of NNK in both liver and lung microsomes. This inhibition correlated with a potent inhibition of MROD and PROD activity in liver but not in lung microsomes. The metabolic activation of NNK is associated with cytochrome P450 isoforms 1A1, 1A2, 2B1, 2D6 and 2E1. Our results suggest that naringenin and quercetin from citrus fruits inhibit the activity of cytochrome P450 (CYP) isoforms that activate NNK and may afford protection against NNK-induced carcinogenesis.

Animals↗
PubMedDate not supplied

Lymphagogue and pulsatile activities of Daflon 500 mg on canine thoracic lymph duct.

An earlier report proved that Daflon 500 mg constituted of 90% diosmin and 10% hesperidin exerts a lymphagogue effect on dogs. The aim of the present work is to investigate whether the lymphagogue effect of Daflon 500 mg is associated with an increase in pulsatile activity of lymphatic vessels. The investigation was carried out on mongrel dogs anaesthetised by pentobarbital (10 mg/kg); the lymph was collected by a fistula on the thoracic lymphatic duct; using this fistula the pulsatile activity of lymphatic vessels was estimated by Campbell and Health methodology. The lymphatic volume was measured every ten-minutes in graduated tubes for 2 hours and the pulsatile component of intralymphatic pressure (MPC) was estimated from measurements of the area (expressed in mm2) enclosed by the part of the tracing due to the pulsatile component during one minute. Daflon 500 mg was intravenously injected after having been dissolved in DMSO + TRIS; three doses were injected: 12.5, 6.25 and 3.125 mg/kg. Regarding the lymphagogue effect, Daflon 500 mg induced an increase in lymphatic flow correlated with the administered doses. The maximal 10-minute period lymphatic flows were 191% (12.5 mg/kg), 171% (6.25 mg/kg) and 91% (3.125 mg/kg); the peak of the effect was, in each case, reached between 20 and 25 minutes after the injection. Regarding the pulsatile activity, Daflon 500 mg induced an increase of MPC. The MPC was correlated with the increase in lymph flow (r = 0.877).

Animals↗
PubMedDate not supplied

Effects of Daflon 500 mg on bovine vessels contractility.

The effect of Daflon 500 mg, consisting of 90% diosmin and 10% hesperidin, on bovine veins and lymphatic vessels was shown. The recording of mechanical tension on metacarpal vein rings demonstrated a dose-effect relationship with an ED50 of 0.5 X 10(-6) M. This effect observed on isolated organs, is close to the tonic effect of Daflon 500 mg observed in human. An effect was also observed as demonstrated by the depolarisation curve obtained after administration of solutions containing increasing concentrations of potassium. The curve was shifted to the right which may indicate a decrease in potassium permeability in the presence of Daflon 500 mg. On lymphatic vessels isolated from mesenterium, the main effect was an increase in the frequency of spontaneous response which could explain the effect of Daflon 500 mg on lymph flow as shown previously. This dose-effect relationship could be due to an increase in the sensitivity of receptors to some agonists. However, this effect could be pleiotropic. This pleiotropic effect could involve the stimulation by Daflon 500 mg of other cellular mechanisms such as phosphatidylinositol metabolism, or more directly, the pacemaker activity of the cells which govern spontaneous activity, pacemaker activity being under the control of membrane potassium permeability. Some evidence about the action of Daflon 500 mg on potassium permeability could also be shown on other tissues.

Animals↗
PubMedDate not supplied

Biochemical mediators involved in the inflammatory reaction. Protective activity of S 5682.

Increased vascular permeability of inflammation is accounted for by the formation/release of mediators, such as lipids derived from arachidonate (eicosanoids: prostaglandins, thromboxane A2 or leukotrienes) or from ether phospholipids (PAF-acether). Acute inflammation can be controlled by inhibitors of mediator synthesis or by antagonists, as well as at the level of the reactivity of vascular endothelium or leukocytes. This modulation can be obtained with flavonoids, such as S 5682, a precise fraction of diosmin and hesperidin, which reduces the vascular permeability of the rabbit skin and increases the resistance of rat microvessels. After chronic treatment by the oral route with S 5682, the synthesis of PGE2, PGF2 and TxB2 decreased in inflammatory granuloma in the rat, induced by introducing subcutaneously polyurethane pellets. We carried out studies to see if S 5682 modifies the amounts of TxB2, of PGE2 and of PGI2 formed by perfused guinea-pig lungs injected with PAF-acether (1-100 ng). At 5-50 microM, S 5682 favoured the formation of PGE2 and of prostacyclin, and less that of thromboxane. At higher concentrations, the stimulation of the formation of eicosanoids was less marked, suggesting a biphasic effect. The biosynthetic profile of eicosanoids was affected at low concentrations the flavonoids with a complex and original pattern.

Acute-Phase Reaction↗
PubMedDate not supplied

Effect of a flavonoid preparation (S 5682) on experimental capillary permeability increase in rat paw and rabbit skin.

S 5682 is constituted by a flavonoid mixture of 90% diosmin and 10% hesperidin. Its action has been studied in vivo on microcirculation by measuring experimental alterations of capillary permeability and of venous pressure. Rats were pretreated by IV injection of 25 mg S 5682/kg, one hour before being submitted to a transitory compression of the posterior paw, resulting in reversible oedema that was estimated by plethysmography. The swelling of the paw in pretreated rats was lower than in controls (p less than 0.02), indicating a smaller increase of capillary permeability in rats treated with S 5682. A direct action on capillary permeability has been examined by measuring accumulation of IV injected Evans blue at the site of injection of zymosan, this accumulation was lower in pretreated rats than in controls (p less than 0.05). Similarly, in CFY rats, the pressure required to evoke capillary fragilisation was higher in S 5682 pretreated rats. Evans blue extravasation was also studied in the rabbit in which skin was irritated by topical application of chloroform of by gamma rays. Subcutaneous accumulation of Evans blue was lower in animals pretreated either IV or by oral route than in controls (p less than 0.05). S 5682 has a complex effect on microcirculation as indicated by a smaller increase in femoral venous pressure after ligation of homolateral iliac vein. The above experimental results indicate that S 5682 is acting at the venous side of the microcirculation.

Animals↗
PubMed1994

[Demonstration of the anti-lipid peroxidation effect of 3',5,7-trihydroxy-4'-methoxy flavone rutinoside: in vitro study].

Diosmin (DI) 3'5,7-trihydroxy-4'-methoxy flavone rutinoside is a member of the flavonoid family, some of whom have antioxidant or free radical scavenger properties. Paw oedema induced by doxorubicin in rats is reduced by DI as observed by SAUVAIRE et al (1989). This suggests a free radical scavenger activity for DI. In this work we demonstrate that such activity is able to protect isolated human LDL from oxidation in vitro. The study of the electrophoretic mobility of oxidized LDL and of total-MDA values as lipoperoxidation-marker indicates an oxidation inhibiting effect higher than 70% for 0.16 mM DI in LDL mixtures containing 50 mM Cu2+ or 4.3 mU/ml xanthine-oxidase and incubated during 20 and 6 hours respectively. Owing to the high level of the oxidizing conditions and the vitamin E (48 mM), vitamin A (1.4 mM) and beta-carotene (2.4 mM) content of the LDL mixtures, it is concluded that DI is clearly able to complement the antioxidant effect of isoprenoids which are naturally present in LDL mixtures.

Adult↗
PubMed1994

Pharmacologic properties of Daflon 500 mg.

AIMS AND METHODS: Some pharmacologic activities of a micronized flavonoid complex consisting of 90% diosmin + 10% hesperidin (Daflon 500 mg*) have been investigated by use of various experimental models: (1) interference with mechanisms of edema (synthesis of arachidonic acid derivatives, microvascular hyperpermeability induced by bradykinin, ischemia, or streptozotocin), (2) interference with lymphatic drainage (thoracic duct fistula in the dog). RESULTS: Daflon 500 mg inhibited prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) synthesis during a one-month oral daily treatment (100 mg.kg-1.day-1) in the rat, after induction of chronic inflammation by subcutaneous implantation of sponge fragments. Microvascular hyperpermeability induced by bradykinin or ischemia in the rat cremaster muscle was reduced after an oral treatment with Daflon 500 mg (100 mg.kg-1 twice daily). Microvascular hyperpermeability of the streptozotocin-induced diabetic rat was antagonized when Daflon 500 mg (300 mg.kg-1 once daily) was given orally as a preventive treatment. In the anesthetized dog, an increase in lymphatic flow, correlated with administered doses, was observed after IV injection of Daflon 500 mg. Lymphatic flow was maximal twenty minutes after injection of the drug (12.5 mg.kg-1) and was three times higher than the basal flow. CONCLUSION: The protective effect of Daflon 500 mg against the formation of perivascular edema and its therapeutic value in the treatment of venous stasis could be explained by its inhibitory activity on the inflammatory process or ischemia-induced hyperpermeability and by its stimulatory effect on the pulsatile activity of lymphatic vessels.

Animals↗
PubMed1994

Controlled studies of Daflon 500 mg in chronic venous insufficiency.

Although great advances have been made in the operative treatment of vascular disorders, the management of most venous problems is still nonsurgical. Daflon 500 mg* is a micronized flavonoid mixture of 90% diosmin and 10% hesperidin that has phlebotonic properties. The efficacy of Daflon 500 mg has been investigated in three double-blind, randomized trials using strain gauge plethysmography to provide quantitative information on venous hemodynamics in patients with chronic venous insufficiency. In total, 183 patients were treated with Daflon 500 mg versus a control group of equal number of patients. Daflon 500 mg produced a significant decrease in venous capacitance, venous distensibility, and venous emptying time (P < 0.001). In addition, these changes were accompanied by improvement in clinical symptoms and a decrease in the supramalleolar circumference. Clinical side effects were rare and led to treatment withdrawal in only 3 patients. It is concluded that Daflon 500 mg is of benefit to patients with chronic venous insufficiency.

Diosmin↗
PubMed1994

Mediators involved in inflammation: effects of Daflon 500 mg on their release.

Each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antiinflammatory effects of Daflon 500 mg,* a micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), were studied in different in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2 alpha (45.2%) and TXB2 (59.5%) (Damon et al, Arzneim-Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of Daflon 500 mg was linked to its ability to scavenge active oxygen radicals, demonstrated in vitro using human neutrophils (Lonchampt et al, Arzneim-forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophages (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at concentrations ranging from 10(-7) M to 10(-4) M, with half-maximal effect between 10(-6) M and 10(-5) M. Thus, Daflon 500 mg behaves as a potent protective agent against inflammatory disorders. These properties may explain, at least in part, the clinical activity of Daflon 500 mg and justify its therapeutic use.

Alloxan↗
PubMed1993

A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility.

The efficacy and safety of a new veno-active flavonoid fraction (S 5682) consisting of micronized diosmin (90%) and hesperidin (10%) have been studied in 100 patients with symptomatic capillary fragility in a double-blind, randomized, placebo-controlled trial. Treatment lasted 6 weeks and consisted of 2 daily tablets of either S 5682 or placebo. Patients were examined at weeks 0, 2, 4 and 6. Compared to placebo, capillary resistance, assessed by the negative suction cup method, was significantly higher in the S 5682 group at week 4 (219 +/- 10 mmHg versus 159 +/- 8 mmHg; p < 0.001) and week 6 (261 +/- 12 mmHg versus 163 +/- 9 mmHg; p < 0.001). This resulted in a significant improvement of symptoms of capillary fragility (spontaneous ecchymosis, epistaxis, purpura, petechiae, gingivorrhagia, metrorrhagia and conjunctival haemorrhage) in S 5682 treated patients (p < 0.001). S 5682 was well tolerated. The rate of side-effects spontaneously volunteered by the patients was similar in both groups. We, therefore, conclude that S 5682 increases to a large extent the capillary resistance in patients with abnormal capillary fragility without significant side-effects.

Aged↗
PubMed1995

The human saphenous vein in pharmacology: effect of a new micronized flavonoidic fraction (Daflon 500 mg) on norepinephrine induced contraction.

Local acidosis (pH 6.4) depresses reactivity of vascular smooth muscle and especially the response of human isolated saphenous veins to exogenous norepinephrine. Experiments were performed to study, under acidosis conditions, the interaction between Daflon 500 mg, a micronized fraction of 90% diosmin and 10% hesperidin, and norepinephrine on human rings of veins. Varicose veins were obtained by conservative varicose veins surgery and normal veins from patients undergoing coronary artery bypass graft surgery. Isometric tension was recorded from venous rings in organ chambers filled with Krebs-Henseleit solution (pH 7.4; 37 degrees C). Metabolic acidosis (from pH 7.4 to 6.4) was obtained by lowering the HCO3- concentration of the Krebs-Henseleit solution. Cumulative concentration-response curves for norepinephrine (10(-7) to 10(-5)M) were obtained at pH 6.4 in the presence or in the absence of Daflon 500 mg (10(-5)M) added 20 min previously to the organ bath. Under acidotic conditions, Daflon 500 mg induced a shift to the left of the concentration-response curves for norepinephrine. This potentiation was significant in both normal and varicose veins and was increased in proportion with the pathological status of the venous rings. These results support the therapeutic benefits of Daflon 500 mg in chronic venous insufficiency.

Acidosis↗
PubMed1998

Micronization: a method of improving the bioavailability of poorly soluble drugs.

For poorly soluble drugs, the digestive absorption depends on their rate of dissolution. Decreasing the particle size of these drugs improves their rate of dissolution. Fine grinding mills are use to micronize powders: either jar mills or fluid energy mills. Theses processes were applied to griseofulvin, progesterone, spironolactone and diosmin. For each drug, micronization improved their digestive absorption, and consequently their bioavailability and clinical efficacy.

Biological Availability↗
PubMed1998

[Study of the pharmacodynamic activity of daflon 500 mg].

Daflon 500 mg, micronized purified flavonoid fraction, composed of 90% diosmin and 10% hesperidin, possesses venotonic and vasculoprotective pharmacological properties, it reinforces venous tone by prolonging the activity of parietal norepinephrine. The pharmacodynamic properties of Daflon 500 mg were demonstrated by mercury stress gauge venous occlusion plethysmography during a double-blind placebo-controlled trial in 10 women not presenting any venous disease. Venous tone was significantly reinforced by the 1st hour after a single dose of 2 tablets of Daflon 500 mg. This effect persisted for 4 to 24 hours according to the mode of administration. The rapid action of Daflon 500 mg is due to micronization of its active ingredient into particles less than 2 microns, thereby considerably increasing its absorption.

Adult↗
PubMed2001

Efficacy of Micronized Flavonoid Fraction in Healing of Clean and Infected Wounds.

Purified micronized flavonoid fraction, comprising 90% diosmin and 10% hesperidin, is basically used as a phelebotonic and vasculoprotector agent. It also has anti-inflammatory and anti-edematous actions. This study was designed to evaluate the efficacy of micronized flavonoid fraction in clean and infectious wounds. Sixty Guinea pigs were separated into 2 main groups and 6 subgroups. The first three groups had clean wounds and the other three groups had infected wounds contaminated with S. aureus. Then these main groups were separated into 3 subgroups. The first subgroups was treated with 60 mg/kg/day micronized flavonoid fraction per oral, the second ones was treated with topical 60 mg/kg/day micronized flavonoid fraction, and the third ones had no treatment. Infected wounds were obtained by contamining the wounds with S. aureus. There were no significant differences in wound healing between the groups that have clean wounds (p > 0.05). In the groups with infected wounds, orally and topically treated guina pigs had accelerated wound healing compared to the untreated control group (p < 0.05), confirmed with surface area measurements and histopathological evaluation. Healing showed no difference between the groups treated orally and topically. This study showed that oral or topical administration of micronized flavonoid fraction in the infected wounds is beneficial, while it has no significant effect in clean wounds. </hea

Journal Article↗