Chronic venous insufficiency (CVI) affects a large number of people in Western countries, and is responsible for considerable inconvenience, discomfort, suffering, and costs. Micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin-Daflon 500 mg) is a potent venotropic drug used in the treatment of venous insufficiency. Pharmacological and clinical studies demonstrated the comprehensive mode of action of Daflon 500 mg: it increases venous tone, it improves lymph drainage, and it protects the microcirculation. Clinical international, prospective, multicenter, randomized, controlled studies versus placebo studies documenting the effects of Daflon 500 mg in CVI at advanced stages with edema, skin changes, and venous leg ulcer are reviewed. In edema, one of the most frequent complaints of patients, Daflon 500 mg brings about a significant reduction in leg circumference, thanks to its capacity to inhibit inflammatory reactions and to decrease capillary hyperpermeability. The rationale for the use of Daflon 500 mg for treatment of skin disorders and venous leg ulcer is its action on the microcirculation-damaging processes. Regarding skin changes, Daflon 500 mg has been shown to improve venous trophic disorders, like gravitational (stasis) dermatitis, and dermatofibrosclerosis. In venous leg ulcer, Daflon 500 mg's clinical efficacy has been demonstrated in addition to standard treatment or versus standard treatment alone. Daflon 500 mg, thanks to its comprehensive mode of action on the veins, lymphatics, and microcirculation, is the method of choice not only in the early stages of CVI treatment, but also in the severe stages of this condition, in combination with compression treatment, sclerotherapy, and surgery if appropriate.
"Diosmin, a naturally occurring flavonoid glycoside, was first isolated in 1925 from Scrophularia nodosa, and first introduced as a therapeutic agent in 1969. As a vascular-protecting agent, its mechanisms of action include improvement of venous tone, increased lymphatic drainage, protection of capillary bed microcirculation, inhibition of inflammatory reactions, and reduced capillary permeability –. This agent reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1), and inhibits the adhesion, migration, and activation of leukocytes at the capillary level. "
[Show abstract][Hide abstract] ABSTRACT: Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury.
Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy.
Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio.
Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.
PLoS ONE 04/2013; 8(4):e61794. DOI:10.1371/journal.pone.0061794 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SUMMARY Background: Melanoma metastasizes in approximately one third of patients, causing a drop in survival of 1-2% at two years. The only effective treatment is Interferon alpha (IFN α) at elevated doses, which is highly toxic. Thus, less toxic antitumoral agents are being sought, among which fla- vonoids are to be highlighted. Our aim was to study the combined treatment of metastasic lung melanoma with IFN α and diosmin in a murine model. Material & Methods: 60 Swiss mice inoculated with cells (5 x 105) from the B16F10 murine melanoma cell line, treated over 11 days prior and 21 days following inoculation: Group I: ethanol + PBS; Group II: ethanol + IFN α (600,000 IU); Group III: ethanol + IFN α (1,200,000 IU); Group IV: dios- min + PBS; Group V: diosmin + IFN α (600,000 IU); Group VI: diosmin + IFN α (1,200,000 IU). Following treatment, animals were sacrificed and a macroscopic count of sub- pleural metastasic nodules was performed. Results: We found significant differences between the control and the treated groups (p
[Show abstract][Hide abstract] ABSTRACT: Chronic venous insufficiency (CVI) occurs in a relatively large proportion of the population and is associated with significant morbidity, high cost of healthcare, loss of productivity and reduced quality of life. Lower extremity ulcers related to CVI have been estimated to affect 0.21% of the population in developed countries. The prevalence of venous ulcers in the US is estimated at 500 000600 000, and increases with age. Estimates of the annual incidence of leg ulcer in the UK and Switzerland are 3.5 and 0.2 per 1000 individuals, respectively. Treatment of venous ulcers can be expensive, leading to a large economic burden on health services in many countries. The annual cost of CVI is estimated to be more than $US1 billion in the US and between £400600 million in the UK. Current treatments for CVI include surgery, sclerotherapy, compressive therapy (conventional therapy) and adjuvant pharmacotherapy. Various pharmacological agents have been used as adjuvant therapy but in many cases there is no definitive evidence of their efficacy.Effective treatment programs for venous leg ulcers could substantially reduce the economic impact of CVI on health services. In controlled studies, micronized purified flavonoid fraction (MPFF) adjuvant therapy has been shown to increase significantly the number of healed venous leg ulcers and to reduce significantly the healing time of ulcers compared with conventional therapy alone, potentially leading to an improvement in patients quality of life. The treatment of venous leg ulcers with MPFF was also found to reduce overall treatment costs compared with conventional therapy alone. In a retrospective cost-effectiveness analysis based on direct medical costs only, MPFF therapy improved the cost-effectiveness ratio by 45% compared with conventional therapy. If intangible costs, such as loss of quality of life were included, the difference in cost-effectiveness ratios is likely to be even greater in favor of MPFF. Sensitivity analyzes showed that even with a 20% increase in drug price the cost-effectiveness ratio for MPFF therapy was substantially better than that for conventional therapy ($US1061.8 vs 1871.9 per ulcer healed). Hence, the addition of MPFF adjuvant therapy to the treatment of venous leg ulcers would be effective and potentially cost saving.
American Journal of Clinical Dermatology 12/2002; 4(8):573-581. DOI:10.2165/00128071-200304080-00007 · 2.73 Impact Factor
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