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PubMed1991

Daflon as a cellular antioxidant and a membrane-stabilizing agent in human fibroblasts irradiated by ultraviolet A radiation.

Daflon is a strong inhibitor of Cu(2+)-induced arachidonic acid peroxidation, as revealed by the inhibition of thiobarbituric acid-reactive substance formation in mixed liposomes of phosphatidylcholine and arachidonic acid. Diosmin, the major Daflon constituent, is a good complexant of Cu2+ ions but not of Fe2+ ions. The Cu2+ complex formation may thus explain part of the antioxidant effect. However, Daflon is also a good quencher of the singlet oxygen-induced arachidonic acid peroxidation that does not involve metal ions. When cultured human fibroblasts are incubated with the diosmin-hesperidin mixture constituting Daflon, the latter is as efficient as vitamin E in inhibiting the ultraviolet A-induced lipid peroxidation and plasma membrane damage measured by lactate dehydrogenase release.

Antioxidants↗
PubMed1994

[In vivo study of the antilipoperoxidant effect of 3',5,7-trihydroxy-4'-methoxy flavone 7 rutinoside].

In 3-month-old Wistar rats carrageenan and CCl4 injected intraperitoneally induce an acute phase reaction which is characterized by a marked increase in alpha 1, alpha 2, beta serum globulins. This reaction corresponds to a large increase in these globulins in the first case and a smaller one in the second. A lipoperoxidant effect is demonstrated by the serum lipoprotein mobility as the lipoperoxidation index (in MDA units) or the decrease in serum vitamin A and E concentrations. This effect is also greater in the first case than in the second one. In the same way the lipoperoxidant effect is shown in liver microsomes but with a lower amplitude in the first case than in the second one. The treatment of rats by intraperitoneal injection of diosmine (150 mg/kg per week) during the 8 weeks which precede the injection of carrageenan or CCl4 results in: i) a marked decrease in the acute-phase reaction and a lower one in the lipoperoxidant effect, in serum; ii) a decrease in the CCl4 induced lipoperoxidant effect in liver microsomes. It may be concluded that diosmine, not injected at the same time as carrageenan or CCl4, but during the previous 8 weeks is sufficiently well distributed in the whole body to produce a marked inhibition of the acute phase reaction and a perceptible effect on lipoperoxidation. It may be considered an effective complement to the natural antioxidant defences of the organism (vitamins A and E).

Acute-Phase Reaction↗
PubMed1998

Modulation by phytochemicals of cytochrome P450-linked enzyme activity.

Compounds derived from plant sources with putative anticancer properties were studied for their effects on alkoxyresorufin O-dealkylase activity, a measure of cytochrome P450 activity. The phytochemicals investigated included benzyl isothiocyanate, caffeic acid, chlorogenic acid, diosmin, ferulic acid, indole-3-carbinol, phenethyl isothiocyanate and resveratrol. Each phytochemical at concentrations of 0.25 and 0.5 microM was incubated with 0.2 mg hamster liver microsomal protein and 0.5 microM concentrations of benzyloxyresorufin, ethoxyresorufin and methoxyresorufin. Three of the phytochemicals tested, namely benzyl isothiocyanate, phenethyl isothiocyanate and resveratrol, exhibited potent inhibition of alkoxyresorufin O-dealkylase activity. Benzyl isothiocyanate inhibited benzyloxyresorufin O-dealkylase (BROD) activity, ethoxyresorufin O-deethylase (EROD) activity and methoxyresorufin O-demethylase (MROD) activity by 90% at both the 0.25 and 0.5 microM concentrations. Phenethyl isothiocyanate inhibited BROD activity by 69%, EROD activity by 90% and MROD activity by 94% at both concentrations tested. Resveratrol inhibited BROD activity by 69% at the 0.25 microM concentration and by 78% at the 0.5 microM concentration. It inhibited EROD activity by 60% at the 0.25 microM concentration and by 80% at the 0.5 microM concentration. Resveratrol exhibited the greatest inhibitory action toward MROD, i.e. 76% and 84% at the two concentrations tested. Chlorogenic acid significantly affected BROD, EROD and MROD activity only at the 0.5 microM concentration inhibiting by 51%, 47% and 54%, respectively. Caffeic acid affected BROD and MROD activity at 0.5 microM only inhibiting BROD activity by 46% and MROD activity by 40%. Diosmin inhibited EROD activity by 11% at the 0.25 microM concentration and by 61% at 0.5 microM. It inhibited MROD by 47% and 54% at the two concentrations tested but did not significantly alter BROD activity. Ferulic acid significantly inhibited EROD and MROD activity at the 0.5 microM concentration by 28% and 32%, respectively. Indole-3-carbinol significantly inhibited BROD activity by 26% at 0.25 microM and by 42% at 0.5 microM. It inhibited EROD and MROD activity by 28% and 29% at 0.5 microM, respectively. The alkoxyresorufin O-dealkylase reactions are selective for various isoforms of cytochrome P450. Our results suggest that the phytochemicals we tested have varied effects on the enzymatic activity of isoforms of cytochrome P450 that dealkylate benzyloxyresorufin, methoxyresorufin and ethoxyresorufin and therefore may have varied effects on the metabolism of substrates for these isoforms.

Animals↗
PubMed2004

Flavonoid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. postulation of a biosynthetic pathway.

The distribution of seven flavonoids, eriocitrin, luteolin 3'-O-beta-d-glucuronide, hesperidin, diosmin, isoscutellarein 7-O-glucoside, hispidulin 7-O-glucoside, and genkwanin, has been studied in Rosmarinus officinalis leaves, flowers, stems, and roots during plant growth. The maximum level reached by luteolin 3'-O-beta-d-glucuronide in leaves during June-August suggests the existence of a delay between the activation of the enzymes involved in the flavanone and flavone biosynthesis. The presence of hesperidin and diosmin in the vascular system is significant, and hesperidin shows even higher levels than the phenolic diterpenes and rosmarinic acid. The distribution of flavonoids observed in R. officinalis suggests a functional and structural relationship between phytoregulators and flavonoids, where flavonoids would be "protectors" of the activity of phytoregulators. A hypothesis for the general pathway of biosynthesis of these compounds in plants of the family Labiatae is proposed.

Chromatography, High Pressure Liquid↗
PubMed2000

Antioxidant activity and radioprotective effects against chromosomal damage induced in vivo by X-rays of flavan-3-ols (Procyanidins) from grape seeds (Vitis vinifera): comparative study versus other phenolic and organic compounds.

The quantitative distribution of several flavan-3-ols was determined using HPLC in a grape (Vitis vinifera) seed extract (GSE) of four cultivars grown in the region of Murcia. Polymer >/= C(4) units made up the largest group of procyanidins in the GSE (90.92%, expressed as HPLC % area). The antioxidant activity of GSE and other reference compounds was investigated by measuring their ability to scavenge the ABTS(*)(+) radical cation (TEAC). The most effective compounds were, in order: GSE > rutin > (+)-catechin > diosmin >/= ascorbic acid. The radioprotective effects of GSE and other reference compounds were determined by using the micronucleus test for anticlastogenic activity, any reduction of the frequency of micronucleated polychromatic erythrocytes (MnPCEs) being evaluated in the bone marrow of mouse exposed to X-rays. The most effective compounds were, in order: GSE > rutin > dimethyl sulfoxide (DMSO) > ascorbic acid > 6-n-propyl-2-thiouracil-6c (PTU) > diosmin. The higher ABTS(*)(+) scavenging capacity and anticlastogenic activity of GSE can be explained, structurally, by the high number of conjugated structures between the catechol groups in the B-rings and the 3-OH free groups of the polymeric polyphenolic skeleton and, in addition, by the stability of the aroxyl flavonoid radical generated in the above processes.

Animals↗
PubMed2003

Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.

Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin. We also investigated the AhR-dependent activities of cantharidin and emodin (in herbal extracts) in Ah-responsive MCF-7 human breast cells, HepG2 human liver cancer cells, and mouse Hepa-1 cells transiently or stably transfected with plasmids expressing a luciferase reporter gene linked to multiple copies of a consensus dioxin-responsive element. The AhR agonist activities of the compounds (1 and 10 micro M) were as high as 25% of the maximal response induced by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their potencies were dependent on cell context. Galangin, genistein, daidzein, and diosmin were active only in Hepa-1 cells, and cantharidin induced activity only in human HepG2 and MCF-7 cells. Western blot analysis confirmed that baicalein and emodin also induced CYP1A1 protein in the human cancer cell lines. The AhR antagonist activities of four compounds inactive as agonists in MCF-7 and HepG2 cells (kaempferol, quercetin, myricetin, and luteolin) were also investigated. Luteolin was an AhR antagonist in both cell lines, and the inhibitory effects of the other compound were dependent on cell context. These data suggest that dietary phytochemicals exhibit substantial cell context-dependent AhR agonist as well as antagonist activities. Moreover, because phytochemicals and other AhR-active compounds in food are present in the diet at relatively high concentrations, risk assessment of dietary toxic equivalents of TCDD and related compounds should also take into account AhR agonist/antagonist activities of phytochemicals.

Animals↗
PubMedDate not supplied

[A comparative study of the protective effect of various phlebotonic agents on hypoxic endothelial cells].

Many findings indicate that the etiology of venous disease is multifactorial. One of the chief factors is certainly the stasis of blood in the lower limbs during long periods of standing. This stasis causes tissue hypoxia which first affects the venous wall. Because of their site at the blood/vein wall interface as well as their fragility, endothelial cells are the first to suffer from lack of oxygen. In order to understand these events, the authors have developed a model of endothelial cells in culture subjected to hypoxia in vitro which imitates conditions encountered clinically. This model was used to test different drugs commonly used in venous pathology. These included GbE, the active ingredient of GINKOR FORT, diosmine and procyanidolic oligomers. It was thus shown that only GbE was not toxic to endothelial cells. Furthermore, GbE was capable of effectively protecting cells subjected to hypoxia. Protection with diosmine was obtained only at concentrations very close to toxic doses. In contrast, procyanidolic oligomers afforded no protection. The protective effect of GbE is believed to be due to the action of terpenes on cellular energy metabolism.

Antihypertensive Agents↗
PubMed1995

Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy.

A prospective randomized controlled trial was carried out on the effects of Daflon 500 mg (a micronized flavonidic fraction containing diosmin 450 mg and hesperidin 50 mg) on bleeding after haemorrhoidectomy. In all, 228 consecutive patients with prolapsed irreducible piles were recruited. Elective haemorrhoidectomy was performed with a standardized diathermy excision method. Some 114 patients were randomized to receive Daflon 500 mg for 1 week after operation (group 1), and there were 114 controls (group 2). Postoperative analgesia and laxative prescription as well as hospital stay were otherwise the same. One patient (0.9 per cent) from group 1 and seven (6.1 per cent) from group 2 had postoperative bleeding (P = 0.03). All bleeding occurred from 6 to 15 days after haemorrhoidectomy. There were no side-effects from the use of Daflon 500 mg. The risk of secondary bleeding from haemorrhoidectomy is reduced with postoperative Daflon.

Adult↗
PubMed1992

Thermal behavior and elastic properties of phospholipid bilayers under the effect of a synthetic flavonoid derivative, LEW-10.

We have investigated the effect on phospholipidic bilayers of LEW-10, a synthetic flavonoid, derivative of diosmin. Two optical techniques, Quasi-elastic Light Scattering (QLS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used. The results show that in the presence of LEW-10, the phase transition of the bilayers is lowered and that the elastic modulus is decreased. The FT-IR results indicate interactions in the aqueous interface regions of the bilayers. We also discuss LEW-10 comparatively with another derivative, LEW-7/S1, whose effect has been previously studied.

Carbohydrate Sequence↗
PubMed1988

The influence of the fibrinolytic system on the affinity of fibrinogen for the endothelial-plasma interface.

We use intravital fluorescence microscopy to study the endo-endothelial lining of microcirculatory vessels in vivo and in situ (exposed rat mesentery). In earlier experiments we found that fibrinogen had an affinity for the inner lining of microvessels, particularly venules. This affinity was specific to fibrinogen (and fibronectin); most other plasma proteins (albumin, antithrombin III, gamma-globulin) did not accumulate on the inner surface of microcirculatory blood vessels. We postulated the existence of receptors for fibrinogen and/or fibronectin on the endo-endothelial surface, whose turnover rate differed in arterioles and venules. Blockade of the intravascular coagulation process by heparin did not alter the interaction between fibrinogen and endothelium, but blockade of fibrinolytic activity by tranexamic acid increased the deposition of fibrinogen at the endothelial surface. In the present study we administrated a drug containing the bioflavonoids diosmin and hesperidin, which may activate tissue plasminogen activator. Such pretreatment significantly decreased the accumulation of fibrinogen at the endo-endothelial surface of the venules. We therefore conclude that the endothelial plasma interface is characterized by accumulation of fibrinogen which is not affected by thrombin-mediated activation of the coagulation system. In contrast, interactions between fibrinogen and endothelium are influenced by the fibrinolytic system, both of plasmatic and endothelial origin, thus representing an important aspect of the antithrombotic potential of the endothelium.

Animals↗
PubMed2004

[The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration].

The paracetamol and cyclophosphamid are metabolized in the liver by the cytochrome P450. The formed reactive intermediates are responsible of a hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoïds are polyphenols substances of plant origin having some biological and anti-oxydative properties. However no information is available on their effects on glutathion and glutathion-s-transferases. In our research, we valued the effect of oral administration of flavonoids (diosmine and quercetine) under shape of propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way, vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the rat female albinos wistar. We did a blood numeration, an assessment of serum activities of transaminases and alkali phosphatases as well as quantification of the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated. Analyses are done at regular intervals; 1, 3, 7 and 14 days after the administration of drugs. In the group of rats treated by the cyclophosphamid paracetamol alone we observed since the 1st day, an increase of lipid peroxide (MDA) of 120% and a downfall of hepatic glutathion including the group receiving the vinblastine (until 210% of reduction). In the same way a severe leucopenia and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and vinblastine). The combination of flavonoids with drugs have clearly reduced the effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as well as the leucopenia and thrombopenia of the cyclophosphamide are corrected entirely. In the same way, we noted a restoration of rates of peroxide and glutathion. Flavonoïds seem to act by activation of the turn over of the glutathion and enzymes stimulating particularly glutathion-s-transferases permitting the captation of the reactive metabolites of the studied drugs.

Acetaminophen↗
PubMed2003

Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

Acute-Phase Reaction↗
PubMed1999

Effects of the phlebotropic drug Daflon 500 mg on postischemic microvascular disturbances in striated skin muscle: an intravital microscopic study in the hamster.

The objective of this study was to investigate the effects of the micronized purified flavonoid fraction Daflon 500 mg (90% diosmin and 10% hesperidin) on I/R-induced microvascular leukocyte-endothelium interaction and leakage of the high molecular weight plasma tracer FITC-dextran (relative molecular mass, 150 kd) as assessed in the striated skin muscle of the dorsal skin fold chamber model in the hamster. Intravital fluorescence microscopy was used for analysis of microvascular perfusion, leukocyte-endothelium interaction, and macromolecular leakage of FITC-dextran 150 kd in the striated skin muscle of the hamster. A tourniquet ischemia of 4 hours' duration was induced followed by reperfusion. Animals were treated with an oral administration of Daflon 500 mg (n = six) or its vehicle (5% Arabic gum solution, n = six) for 8 days at a daily dose of 30 mg/kg body weight. Measurements in the microcirculation were made before the 8-day feeding protocol before induction of ischemia and at 0.5, 2, and 24 hours of reperfusion. In the absence of I/R, no differences in microvascular perfusion, leukocyte-endothelium interaction, and macromolecular leakage were found in Daflon 500 mg and vehicle-treated control animals before and after administration of the drugs. Induction of ischemia and reperfusion, however, elicited a significant increase in venular leukocyte rolling and sticking in vehicle-treated animals, which was accompanied by enhancement of leakage of FITC-dextran 150 kd into the perivascular tissue. Treatment with Daflon 500 mg had no effect on postischemic leukocyte rolling and sticking, and macromolecular leakage of FITC-dextran 150 kd from arterioles and postcapillary venules was significantly reduced. These data indicate that Daflon 500 mg preserves the endothelial barrier function of striated skin muscle arterioles and venules after I/R, which appears to be independent of an action on postischemic intravascular leukocyte rolling and sticking.

Animals↗
PubMed1999

Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: a histomorphologic study in the hamster.

The objective of this study was to investigate the effects of the purified, micronized, flavonoid fraction Daflon 500 mg (S 5682, 90% diosmin and 10% hesperidin) on tissue damage and leukocyte emigration in striated skin muscle after ischemia-reperfusion, as assessed by histomorphometric analysis. The experimental model used was the transparent dorsal skin fold chamber in the awake Syrian golden hamster. Sixty-four animals were randomly allotted to two treatment groups and time points of investigation. Animals were fed with 30 mg kg(-1) body weight Daflon 500 mg (n = 32) or its vehicle, 5% Arabic gum solution (n = 32), as control 8 hours before ischemia. Before induction of a tourniquet ischemia of 4 hours' duration and at 0.5, 2, and 24 hours of reperfusion, tissue sections were preserved for light and electron microscopic analysis (n = seven or eight animals per time point). The number of intravascular and extravascular leukocytes was determined by light microscopic analysis of esterase-positive leukocytes. For quantitative analysis of ischemia-induced endothelial cell damage, the endothelial thickness of capillaries was calculated by a computer-assisted imaging system, whereas the ischemic tissue damage was assessed by means of a score system (grade 0-3) by an independent investigator. The number of emigrated leukocytes was significantly reduced in Daflon 500 mg-treated animals compared with numbers found in control animals. The histomorphologic muscle fiber damage increased after reperfusion in both groups but was significantly reduced in the Daflon 500 mg-treated animals 2 and 24 hours after reperfusion. These results suggest that the emigration of leukocytes plays an important role in the development of postischemic reperfusion injury of striated skin muscle.

Animals↗
PubMed1998

Effect of long-term treatment with a purified micronized flavonoid fraction on pancreatic mononuclear cell infiltration in diabetic BB rats.

Bio Breeding (BB) rats develop a genetically determined insulin-dependent diabetes, because of the early destruction of pancreatic beta cells of Langerhans islets, massively infiltrated by inflammatory mononuclear cells. S 5682, registered as Daflon, 500 mg, is a purified micronized flavonoid fraction (90% diosmin, 10% hesperidin), which has been shown to possess antiinflammatory properties, including anti-free radical activity, effects on vascular permeability, venous tone, and perivenous inflammation. We studied the effect of S 5682 on the course of pancreatic insulitis in diabetic BB rats. All the diabetic BB rats were hyperglycemic, with an increase of plasma levels of fructosamine, alpha-1 acid glycoprotein, and fibrinogen, and a dramatic decrease of C-peptide level. These parameters were not modified by S 5682. Pancreas histologic studies showed that in S 5682-treated diabetic BB rats, lymphocytic infiltration of Langerhans islets was less important and frequent than in untreated diabetic BB rats. By quantitative analysis, a highly significant difference was observed for insulitis, as well as perivasculitis, between S 5682-treated and untreated diabetic BB rats. This inhibitory effect of S 5682 on pancreatic mononuclear cell infiltration may be useful for a complementary treatment to decrease the development of insulitis in human insulin-dependent diabetes mellitus.

Animals↗
PubMed1999

Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation.

Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the postcapillary venules of the hamster cheek pouch microcirculation. In this study, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were divided into 5 groups (n = 6) and treated orally, twice a day, with placebo (10% lactose solution), S-5682, 5, 20 or 80 mg/kg/day (suspended in 10% lactose solution) or alpha-tocopherol, 1 mg/kg/day, for 10 days prior to the oxidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10(-4) M for 5 min) to hamsters given acridine orange prior to TBOOH resulted in increases in the number of rolling and sticking (no movement for at least 30 s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compared with the placebo group (p > 0.05). On the contrary, leukocyte adhesion was inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or alpha-tocopherol: placebo 105 +/- 3/6 mm(2) (mean +/- SEM); S-5682, 5 mg/kg/day 68 +/- 3/6 mm(2) (p < 0.01), 20 mg/kg/day 55 +/- 3/6 mm(2) (p < 0.001) and 80 mg/ kg/day 39 +/- 2/6 mm(2) (p < 0.001) and alpha-tocopherol 36 +/- 1/6 mm(2) (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher dose of S-5682 was as effective as alpha-tocopherol in inhibiting it.

Animals↗
PubMed1999

Adhesion molecule expression in postischemic microvascular dysfunction: activity of a micronized purified flavonoid fraction.

Ischemia and reperfusion (I/R) induces neutrophil infiltration in skeletal muscle that is localized to the ischemic region. To transmigrate at ischemic regions, granulocytes must first arrest in the postcapillary venular segment of the microcirculation. Initially, leukocytes roll along the endothelium of these venules, a weak adhesive interaction that is mediated by the selectins (L-, E-, and P-selectin). Leukocyte rolling functions to slow the neutrophil during its transit through the microcirculation, thereby allowing it to monitor its local environment for the presence of activating factors arising from the ischemic tissues. When activated, the rolling granulocyte is rendered capable of forming the stronger adhesive interactions that allow the cell to become arrested in postcapillary venules in the ischemic region. These adhesive interactions are mediated by a leukocyte glycoprotein complex designated CD11/CD18 and intercellular adhesion molecule-1 (ICAM-1) expressed on endothelial cells. The stationary neutrophil uses the gradient in concentration of soluble chemoattractants liberated from ischemic tissues as a directional cue to move from the vascular to extravascular compartment, being guided in its transit across the endothelium by interactions with platelet endothelial cell adhesion molecule-1 (PECAM-1), an adhesive molecule localized to the interendothelial cleft. This paper reviews current understanding of the mechanisms underlying the establishment of leukocyte/endothelial cell interactions in postischemic skeletal muscle in terms of specific adhesion molecules that participate in neutrophil sequestration after I/R. Discovery of the molecular determinants of neutrophil/endothelial cell adhesion has uncovered potential mechanisms whereby agents exhibiting anti-adhesive properties may act. The micronized purified flavonoid fraction (450 mg diosmin, 50 mg hesperidin) prevents I/R-induced leukocyte adhesion in skeletal muscle. This anti-adhesive effect appears to be mediated at least in part by inhibition of induced expression of ICAM-1.

Animals↗
PubMed1999

Clinical efficacy of micronized purified flavonoid fraction: an overview.

Flavonoids are widely used for the treatment of chronic venous insufficiency (CVI). In clinical trials, micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin, Daflon 500 mg) has demonstrated its activity in CVI by improving venous tone and vein elasticity assessed by plethysmography. Randomized, double-blind, placebo-controlled clinical studies have shown an improvement in signs and symptoms related to CVI and a decrease in leg circumferences at the levels of the ankle and calf. The effect of MPFF on microcirculatory parameters suspected of participating in the pathophysiological process of venous ulceration has been investigated in patients. These include hemorheological parameters and transcutaneous oxygen tension measurements, which were shown to improve after treatment with MPFF. Finally, a randomized double-blind, placebo-controlled clinical study has shown that MPFF treatment for 2 months, in addition to standard compression therapy, accelerates leg ulcer healing in patients with ulcers </=10 cm.

Animals↗