Summary: A bioflavonoid that strengthens vascular walls.

Top Publications

  1. Jantet G. Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids. Angiology. 2002;53:245-56 pubmed
    ..Patients were treated with micronized purified flavonoid fraction (MPFF), consisting of 450 mg of micronized diosmin and 50 mg of flavonoids expressed in hesperidin over 6 months...
  2. Cesarone M, Belcaro G, Pellegrini L, Ledda A, Di Renzo A, Vinciguerra G, et al. HR, 0-(beta-hydroxyethyl)-rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study. Angiology. 2005;56:1-8 pubmed
    ..study was to investigate differences in efficacy between HR, (0-[beta-hydroxyethyl]-rutosides) and D+H (500 mg, diosmin+hesperidin) in patients with chronic venous insufficiency (CVI)...
  3. Garner R, Garner J, Gregory S, Whattam M, Calam A, Leong D. Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. J Pharm Sci. 2002;91:32-40 pubmed
    Daflon 500 mg, is a micronized purified flavonoid fraction, containing 90% w/w diosmin and 10% w/w of flavonoids expressed as hesperidin, used clinically in the treatment of chronic venous insufficiency and hemorrhoidal disease...
  4. Kharkevich D. [The principles of action and use of phlebotropic agents]. Klin Med (Mosk). 2004;82:4-10 pubmed
  5. Kirienko A, Bogachev V, Zolotukhin I, Golovanova O. [Semisynthetic Diosmin (Phlebodia 600) for therapy of lower limb chronic venous insufficiency]. Angiol Sosud Khir. 2006;12:73-5 pubmed
    The study was held to assess clinical effectiveness of coaggregated semisynthetic Diosmin (Phlebodia 600) for patients with II-III CEAP classes of chronic venous insufficiency (CVI), caused by lower limb variceal diseases...
  6. Quintin J, Lewin G. Semisynthesis of linarin, acacetin, and 6-iodoapigenin derivatives from diosmin. J Nat Prod. 2004;67:1624-7 pubmed
    Semisynthesis of linarin and acacetin from the Citrus flavonoid diosmin was performed via, as first intermediate, the 3'-O-phenyltetrazolyl ether of diosmin...
  7. Pari L, Srinivasan S. Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Biomed Pharmacother. 2010;64:477-81 pubmed publisher
    The purpose of this study was to investigate the effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Diosmin was administered to streptozotocin-induced (45 mg/kg b...
  8. Bergan J, Schmid Schönbein G, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg. Angiology. 2001;52 Suppl 1:S43-7 pubmed
    ..Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and ..
  9. Ramelet A. Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Angiology. 2001;52 Suppl 1:S49-56 pubmed
    ..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...

More Information


  1. Yoo H, Lee M, Chung H, Lee S, Kim D. Effects of diosmin, a flavonoid glycoside in citrus fruits, on P-glycoprotein-mediated drug efflux in human intestinal Caco-2 cells. J Agric Food Chem. 2007;55:7620-5 pubmed
    ..Among the flavonoids tested, diosmin significantly increased the accumulation of rhodamine-123 in Caco-2 cells...
  2. Ciolino H, Wang T, Yeh G. Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity. Cancer Res. 1998;58:2754-60 pubmed
    We investigated the effect of the chemopreventive compound diosmin and its aglycone form, diosmetin, on the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 human breast epithelial cancer cells...
  3. Silambarasan T, Raja B. Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats. Eur J Pharmacol. 2012;679:81-9 pubmed publisher
    The present study was aimed to evaluate the antihypertensive effect of diosmin in deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats...
  4. Manthey J. Biological properties of flavonoids pertaining to inflammation. Microcirculation. 2000;7:S29-34 pubmed
    ..These modes of inhibition provide the mechanisms by which flavonoids inhibit the inflammation response and suggest that this class of molecules may be effective in the treatment of CVI. ..
  5. Dung T, Day C, Binh T, Lin C, Hsu H, Su C, et al. PP2A mediates diosmin p53 activation to block HA22T cell proliferation and tumor growth in xenografted nude mice through PI3K-Akt-MDM2 signaling suppression. Food Chem Toxicol. 2012;50:1802-10 pubmed publisher
    ..This study examines the in vitro and in vivo mechanisms of diosmin on human hepato-cellular carcinoma HA22T cell proliferation inhibition...
  6. el Shafae A, El Domiaty M. Improved LC methods for the determination of diosmin and/or hesperidin in plant extracts and pharmaceutical formulations. J Pharm Biomed Anal. 2001;26:539-45 pubmed
    Two improved, simple, selective and sensitive reversed-phase HPLC methods were developed for the determination of diosmin and hesperidin simultaneously or separately, using external or internal standard techniques, respectively...
  7. Tong N, Zhang Z, Gong Y, Yin L, Wu X. Diosmin protects rat retina from ischemia/reperfusion injury. J Ocul Pharmacol Ther. 2012;28:459-66 pubmed
    b>Diosmin, a natural flavone glycoside, possesses antioxidant activity and has been used to alleviate ischemia/reperfusion (I/R) injury...
  8. Campanero M, Escolar M, Perez G, Garcia Quetglas E, Sadaba B, Azanza J. Simultaneous determination of diosmin and diosmetin in human plasma by ion trap liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: Application to a clinical pharmacokinetic study. J Pharm Biomed Anal. 2010;51:875-81 pubmed publisher
    Diosmetin (3',5,7-trihydroxy-4'-methoxyflavone) is the aglycone of the flavonoid glycoside diosmin (3',5,7-trihydroxy-4'-methoxyflavone-7-ramnoglucoside)...
  9. Martínez Conesa C, Vicente Ortega V, Yáñez Gascón M, Alcaraz Baños M, Canteras Jordana M, Benavente García O, et al. Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin. J Agric Food Chem. 2005;53:6791-7 pubmed
    ..Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered ..
  10. Kanaze F, Gabrieli C, Kokkalou E, Georgarakis M, Niopas I. Simultaneous reversed-phase high-performance liquid chromatographic method for the determination of diosmin, hesperidin and naringin in different citrus fruit juices and pharmaceutical formulations. J Pharm Biomed Anal. 2003;33:243-9 pubmed
    b>Diosmin, hesperidin and naringin are flavonoid glycosides that occur naturally in citrus fruits...
  11. Kumar R, Van Gompel J, Bower R, Rabinstein A. Spontaneous intraventricular hemorrhage associated with prolonged diosmin therapy. Neurocrit Care. 2011;14:438-40 pubmed publisher
    ..b>Diosmin is one such non-FDA approved drug which is a semisynthetic, phlebotropic supplement with multiple ..
  12. Rajnarayana K, Reddy M, Krishna D. Diosmin pretreatment affects bioavailability of metronidazole. Eur J Clin Pharmacol. 2003;58:803-7 pubmed
    To screen for inhibitory effects of diosmin on cytochrome P(450)-mediated metabolism of metronidazole in healthy volunteers. Before/after non-blinded investigation conducted in healthy male volunteers...
  13. Srinivasan S, Pari L. Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chem Biol Interact. 2012;195:43-51 pubmed publisher
    ..The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid ..
  14. Tong N, Zhang Z, Zhang W, Qiu Y, Gong Y, Yin L, et al. Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury. PLoS ONE. 2013;8:e61794 pubmed publisher
    ..b>Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects ..
  15. Bogucka Kocka A, Woźniak M, Feldo M, Kockic J, Szewczyk K. Diosmin--isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use. Nat Prod Commun. 2013;8:545-50 pubmed
    b>Diosmin is a naturally occurring flavone glycoside used in the treatment of venous diseases...
  16. Wojnar W, Kaczmarczyk Sedlak I, Zych M. Diosmin ameliorates the effects of oxidative stress in lenses of streptozotocin-induced type 1 diabetic rats. Pharmacol Rep. 2017;69:995-1000 pubmed publisher
    ..Since diosmin, a plant-derived flavonoid, reveals antioxidative activity, the aim of the study was to investigate if this ..
  17. Savel ev V, Pokrovskii A, Sapelkin S, Bogachev V, Bogdanets L, Zolotukhin I. Micronized diosmin (Detralex) for vein-related trophic ulcers: European experience. Angiol Sosud Khir. 2006;12:53-60 pubmed
    The paper presents a meta-analysis of 5 large European studies (N - 723) on the micronized diosmin administration to patients with venous trophic ulcers (CEAP class VI)...
  18. Massoni F, Cassese M, Nicoletti M, Ricci S. [Rupture of the right ventricular wall closed with Daflon patching and biological glue]. Clin Ter. 2012;163:e177-80 pubmed
  19. Lahouel M, Boulkour S, Segueni N, Fillastre J. [The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration]. Pathol Biol (Paris). 2004;52:314-22 pubmed
    ..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. ..
  20. Prabhu V, Sathyamurthy D, Ramasamy A, Das S, Anuradha M, Pachiappan S. Evaluation of protective effects of diosmin (a citrus flavonoid) in chemical-induced urolithiasis in experimental rats. Pharm Biol. 2016;54:1513-21 pubmed publisher
    Context There have not been any conclusive studies of the effects of diosmin, a modified flavanone glycoside obtained from Teucrium gnaphalodes L'Her (Lamiaceae), on urolithiasis...
  21. Ramelet A. Daflon 500 mg: symptoms and edema clinical update. Angiology. 2005;56 Suppl 1:S25-32 pubmed
    ..controlled study established a statistically significant difference in favor of Daflon 500 mg in comparison with diosmin, both on symptoms and edema...
  22. Danielsson G, Norgren L, Truedsson L, Andreasson A, Danielsson P, Nilsson A, et al. Flavonoid treatment in patients with healed venous ulcer: flow cytometry analysis suggests increased CD11b expression on neutrophil granulocytes in the circulation. Vasc Med. 2003;8:83-8 pubmed
    ..Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days...
  23. Baeshko A, Zhuk G, Orlovskiĭ I, Ulezko E, Savitskaia T, Goretskaia I, et al. [Congenital anomalies of the inferior vena cava: diagnosis and medical treatment]. Angiol Sosud Khir. 2007;13:91-5 pubmed
    ..When the diagnosis of IVC aplasia is confirmed, primary medical treatment should consist in prescribing venotonic agents, elastic compression and in cases of deep veins thrombosis -anticoagulant therapy. ..
  24. Filho L, Menezes P, Santana D, Lima B, Saravanan S, Almeida G, et al. Effect of Pulsed Therapeutic Ultrasound and Diosmin on Skeletal Muscle Oxidative Parameters. Ultrasound Med Biol. 2018;44:359-367 pubmed publisher
    ..From this perspective, the present study aimed to study the inclusion complexes of diosmin in ?-cyclodextrin, chemically quantify the diosmin-in-gel preparation and analyze the stability of the gels...
  25. Perumal S, Langeshwaran K, Selvaraj J, Ponnulakshmi R, Shyamaladevi B, Balasubramanian M. Effect of diosmin on apoptotic signaling molecules in N-nitrosodiethylamine-induced hepatocellular carcinoma in experimental rats. Mol Cell Biochem. 2018;449:27-37 pubmed publisher
    The aim of the present study was to evaluate the antioxidant and chemopreventive efficiency of diosmin against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in adult male rats...
  26. Perera N, Liolitsa D, Iype S, Croxford A, Yassin M, Lang P, et al. Phlebotonics for haemorrhoids. Cochrane Database Syst Rev. 2012;:CD004322 pubmed publisher
    ..However methodological limitations were encountered. In order to enhance our conclusion further, more robust clinical trials which take into account these limitations will need to be performed in the future. ..
  27. Tsukanov I, Tsukanov A. [Results of administering Phlebodia 600 in fertile women with orthostasis-dependent phlebopathy]. Angiol Sosud Khir. 2007;13:107-12 pubmed
    ..Noted was positive dynamics of the preparation with the necessity of continuing to take oral contraceptives by the medical indications. ..
  28. Di Pierro F, Spinelli G, Monsù G, Alvisi G, Bacci G, Baiocchi C, et al. Clinical effectiveness of a highly standardized and bioavailable mixture of flavonoids and triterpenes in the management of acute hemorroidal crisis. Acta Biomed. 2011;82:35-40 pubmed
    ..Moreover, the treatment with Emospid shows to be more effective, if compared with MMDH, in counteracting acute haemorrhoidal crisis. (www.actabiomedica.it) ..
  29. Ahmed S, Mundhe N, Borgohain M, Chowdhury L, Kwatra M, Bolshette N, et al. Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy. Inflammation. 2016;39:1783-97 pubmed publisher
    ..Hence, the present study was designed to explore the nephroprotective nature of diosmin by assessing the various biochemical parameters, markers of oxidative stress and proinflammatory cytokine levels ..
  30. de Souza M, Cyrino F, Mayall M, Virgini Magalhães C, Sicuro F, De Carvalho J, et al. Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon® 500 mg) on microvascular damage elicited by sclerotherapy. Phlebology. 2016;31:50-6 pubmed publisher
    ..This study warrants further investigation for its use in clinical conditions. ..
  31. Cesarone M, Belcaro G, Pellegrini L, Ledda A, Vinciguerra G, Ricci A, et al. Venoruton vs Daflon: evaluation of effects on quality of life in chronic venous insufficiency. Angiology. 2006;57:131-8 pubmed
    ..independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related ..
  32. Parker Athill E, Luo D, Bailey A, Giunta B, Tian J, Shytle R, et al. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol. 2009;217:20-7 pubmed publisher
    ..The current study investigated the effects of luteolin, a citrus bioflavonoid, and its structural analog, diosmin, on IL-6 induced JAK2/STAT3 (Janus tyrosine kinase-2/signal transducer and activator of transcription-3) ..
  33. Rajasekar M, Suresh K, Sivakumar K. Diosmin induce apoptosis through modulation of STAT-3 signaling in 7,12 dimethylbenz(a)anthracene induced harmster buccal pouch carcinogenesis. Biomed Pharmacother. 2016;83:1064-1070 pubmed publisher
    b>Diosmin is naturally found flavanoid in many citrus fruits known to have anti-inflammatory, antihyperglycemic, antioxidant and antimutagenic properties...
  34. Inan A, Sen M, Koca C, Akpinar A, Dener C. The effect of purified micronized flavonoid fraction on the healing of anastomoses in the colon in rats. Surg Today. 2006;36:818-22 pubmed
    ..Although the micronized purified flavonoid fraction has some inhibitory properties on the healing of the anastomosis, its net effect was to obtain a better anastomotic healing of the colon in rats. ..
  35. Saeidi I, Hadjmohammadi M, Peyrovi M, Iranshahi M, Barfi B, Babaei A, et al. HPLC determination of hesperidin, diosmin and eriocitrin in Iranian lime juice using polyamide as an adsorbent for solid phase extraction. J Pharm Biomed Anal. 2011;56:419-22 pubmed publisher
    Solid phase extraction (SPE) and HPLC were used for simultaneous determination of hesperidin, diosmin and eriocitrin in Iranian lime juice samples...
  36. Nicolaides A. From symptoms to leg edema: efficacy of Daflon 500 mg. Angiology. 2003;54 Suppl 1:S33-44 pubmed
    ..Daflon 500 mg, a well-established oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin, may be prescribed from the very beginning of the disease for the ..
  37. Cengiz A, Tabak S, Kuru S, Demirel A, Barlas A, Altun T, et al. Effects of diosmine-hesperidine on experimental colonic anastomosis. Bratisl Lek Listy. 2012;113:692-7 pubmed
    ..The administration of diosmine-hesperidine increased the amount of collagen and bursting pressures at the anastomotic site and thus had favorable influences on the healing of colonic anastomosis (Tab. 1, Fig. 3, Ref. 33). ..
  38. Sakalli S, Burkina V, Pilipenko N, Zlabek V, Zamaratskaia G. In vitro effects of diosmin, naringenin, quercetin and indole-3-carbinol on fish hepatic CYP1A1 in the presence of clotrimazole and dexamethasone. Chemosphere. 2018;192:105-112 pubmed publisher
    ..Therefore, this study was designed to determine the effects of diosmin, naringenin, quercetin and idole-3-carbinol on CYP1A-dependent 7-ethoxyresorufin-O-deethylase (EROD) activity on ..
  39. Mendel M, Chłopecka M, Dziekan N, Karlik W. Antispasmodic effect of selected Citrus flavonoids on rat isolated jejunum specimens. Eur J Pharmacol. 2016;791:640-646 pubmed publisher
    ..Hesperetin and diosmetin, but not hesperidin and diosmin, dose-dependently (10-100µM) and reversibly inhibited acetylcholine (1µM) and KCl (80mM) induced contractile ..
  40. Lewinska A, Adamczyk Grochala J, Kwasniewicz E, Deregowska A, Wnuk M. Diosmin-induced senescence, apoptosis and autophagy in breast cancer cells of different p53 status and ERK activity. Toxicol Lett. 2017;265:117-130 pubmed publisher
    ..PR-, HER2-) and SK-BR-3 (ER-, PR-, HER2+), and diosmin, a citrus fruit flavonoid belonging to a flavone subclass, was selected...
  41. Marin F, Del Rio J. Selection of hybrids and edible citrus species with a high content in the diosmin functional compound. Modulating effect of plant growth regulators on contents. J Agric Food Chem. 2001;49:3356-62 pubmed
    ..of this study is to identify species, hybrids, and cultivars of edible Citrus species with high contents of diosmin as a functional compound and also to identify the developmental progress of the fruit in which it reaches maximum ..
  42. Galley P, Thiollet M. A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility. Int Angiol. 1993;12:69-72 pubmed
    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, ..
  43. Hosseinimehr S, Ahmadi A, Mahmoudzadeh A, Mohamadifar S. Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytes. Environ Mol Mutagen. 2009;50:749-52 pubmed publisher
    ..These findings suggest the possible application of Daflon for the protection of human lymphocytes from the genetic damage and side effects induced by gamma irradiation. ..
  44. Bedada S, Neerati P. Modulation of CYP3A enzyme activity by diosmin and its consequence on carbamazepine pharmacokinetics in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391:115-121 pubmed publisher
    b>Diosmin is a widely used flavonoid for the treatment of varicose veins and hemorrhoids...
  45. Trent J, Falabella A, Eaglstein W, Kirsner R. Venous ulcers: pathophysiology and treatment options. Ostomy Wound Manage. 2005;51:38-54; quiz 55-6 pubmed
    ..The epidemiology, pathophysiology, diagnosis, and management options regarding venous ulcers are reviewed. ..
  46. Bouskela E, Cyrino F, Lerond L. Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation. J Vasc Res. 1999;36 Suppl 1:11-4 pubmed
    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...
  47. Struckmann J. Clinical efficacy of micronized purified flavonoid fraction: an overview. J Vasc Res. 1999;36 Suppl 1:37-41 pubmed
    ..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 ..
  48. Ting A, Cheng S, Wu L, Cheung G. Clinical and hemodynamic outcomes in patients with chronic venous insufficiency after oral micronized flavonoid therapy. Vasc Surg. 2001;35:443-7 pubmed
    ..In this regard, Daflon would be especially useful for symptomatic relief in patients with functional venous insufficiency who do not have clinical evidence of varicose veins but suffer from symptoms of venous insufficiency. ..
  49. Ishikawa M, Kawasaki M, Shiono Y, Koseki T. A novel Aspergillus oryzae diglycosidase that hydrolyzes 6-O-?-L-rhamnosyl-?-D-glucoside from flavonoids. Appl Microbiol Biotechnol. 2018;102:3193-3201 pubmed publisher
    ..However, no activity was found with naringin, diosmin, monoglycosylated chromogenic substrates, and polymeric laminarin substrate...
  50. Başoğlu M, Eren E, Aslan H, Bingölballı A, Oztürkcan S, Katilmiş H. Prevention of cisplatin ototoxicity: Efficacy of micronized flavonoid fraction in a guinea pig model. Int J Pediatr Otorhinolaryngol. 2012;76:1343-6 pubmed publisher
    ..01). Micronized flavonoid fraction (Daflon) is effective against cisplatin-induced ototoxicity in guinea pigs. ..
  51. Kuznetsov M, Sapelkin S, Boldin B, Leont ev S, Neskhodimov L. [Recanalization of lower-limb deep veins as an index of efficacy of treatment for acute venous thrombosis]. Angiol Sosud Khir. 2016;22:82-8 pubmed
    ..followed by switching to indirect anticoagulants (warfarin) combined with venotonics (original highly-purified diosmin 600 mg once daily)...
  52. Korthui R, Gute D. Anti-inflammatory actions of a micronized, purified flavonoid fraction in ischemia/reperfusion. Adv Exp Med Biol. 2002;505:181-90 pubmed
    ..In addition, it appears that these compounds prevent the expression of specific adhesion molecules involved in leukocyte recruitment, observations which provide the molecular basis for the anti-adhesive properties of these compounds. ..
  53. Pokrovsky A, Saveljev V, Kirienko A, Bogachev V, Zolotukhin I, Sapelkin S, et al. Surgical correction of varicose vein disease under micronized diosmin protection (results of the Russian multicenter controlled trial DEFANS). Angiol Sosud Khir. 2007;13:47-55 pubmed
    ..The main group (n=200) received micronized diosmin (Detralex, 1000 mg/day) for 2 weeks before and 30 days after the procedure; control group (n=45) did not receive ..
  54. Rehman M, Tahir M, Quaiyoom Khan A, Khan R, Lateef A, Hamiza O, et al. Diosmin protects against trichloroethylene-induced renal injury in Wistar rats: plausible role of p53, Bax and caspases. Br J Nutr. 2013;110:699-710 pubmed publisher
    b>Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties...
  55. Tanrikulu Y, Kismet K, Serin Kilicoglu S, Devrim E, Erel S, Sen Tanrikulu C, et al. Diosmin ameliorates intestinal injury induced by hepatic ischemia reperfusion in rats. Bratisl Lek Listy. 2011;112:545-51 pubmed
    Hepatic ischemia-reperfusion causes histologic injury to the intestinal mucosa. We investigated the effects of diosmin, a phelobotrophic drug with antioxidant and antiinflammatory effects, on intestinal injury in the experimental liver ..
  56. Rajnarayana K, Reddy M, Vidyasagar J, Krishna D. Study on the influence of silymarin pretreatment on metabolism and disposition of metronidazole. Arzneimittelforschung. 2004;54:109-13 pubmed
    ..Urinary excretions of acid-metronidazole (AM), HM as well as metronidazole in 48 h were decreased. The results indicate that silymarin might induce both intestinal P-glycoprotein and CYP3A4 upon multiple dose administration. ..
  57. Freag M, Elnaggar Y, Abdallah O. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation. Int J Nanomedicine. 2013;8:2385-97 pubmed publisher
    b>Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma...
  58. Jain D, Bansal M, Dalvi R, Upganlawar A, Somani R. Protective effect of diosmin against diabetic neuropathy in experimental rats. J Integr Med. 2014;12:35-41 pubmed publisher
    The present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats...
  59. Murashov A, Buriukov R, Khokhlova O, Medvedev O. [Effect of daflon on the transcapillary fluid exchange in hindlimbs of anesthesized Wistar rats]. Eksp Klin Farmakol. 2001;64:67-8 pubmed
    ..The treatment reduced the level of fluid filtration from the vascular channel to the interstitial space, but did not affect the level of reabsorption. ..
  60. Pascarella L, Lulic D, Penn A, Alsaigh T, Lee J, Shin H, et al. Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg. Eur J Vasc Endovasc Surg. 2008;35:102-10 pubmed
    ..MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension. ..
  61. Smith P. Daflon 500 mg and venous leg ulcer: new results from a meta-analysis. Angiology. 2005;56 Suppl 1:S33-9 pubmed
    ..These results confirm that venous ulcer healing is accelerated by Daflon 500 mg treatment. Daflon 500 mg might be a useful adjunct to conventional therapy in large and longstanding ulcers that might be expected to heal slowly. ..
  62. Zhang Y, Jiang S, Xu K, Shi H, Zhou Y, Deng W, et al. [Chemical constituents contained in seeds of Notopterygium franchetii]. Zhongguo Zhong Yao Za Zhi. 2012;37:941-5 pubmed
    ..V (23), 8-O-beta-D-glucopyranosyl-5-hydroxypsoralen (24), 8-O-beta-D-glucopyranosyl-5-methoxylpsoralen (25), diosmin (26), alaschanioside C (27), kynurenic acid (28) and mannitol (29)...
  63. Godfraind T. Effect of a flavonoid preparation (S 5682) on experimental capillary permeability increase in rat paw and rabbit skin. Int Angiol. 1988;7:17-9 pubmed
    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...
  64. Kilicoglu S, Tanrikulu Y, Kismet K, Devrim E, Erel S, Tanrikulu C, et al. The effect of diosmin on pancreatic injury induced by hepatic ischemia reperfusion in rats. Bratisl Lek Listy. 2013;114:119-24 pubmed
    ..Antibacterial suture is not superior to the conventional suture. It is concluded that cyanoacrylate is not an appropriate molecule for abdomen closure (Tab. 1, Fig. 3, Ref. 17). ..
  65. Frick R. Three treatments for chronic venous insufficiency: escin, hydroxyethylrutoside, and Daflon. Angiology. 2000;51:197-205 pubmed
    ..With regard to similarity, no differences in effect have been established among these phlebotonics. ..
  66. Nolte D, Pickelman S, Schütze E, Möllmann M, Messmer K. Effects of Daflon 500mg on postischemic macromolecular leak syndrome in striated skin muscle of the hamster. Int J Microcirc Clin Exp. 1997;17 Suppl 1:6-10 pubmed
    We have recently shown that the purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) Daflon 500 mg attenuates reperfusion injury in the striated skin muscle of the hamster...
  67. Martinez C, Vicente V, Yanez J, Alcaraz M, Castells M, Canteras M, et al. The effect of the flavonoid diosmin, grape seed extract and red wine on the pulmonary metastatic B16F10 melanoma. Histol Histopathol. 2005;20:1121-9 pubmed publisher
    ..Swiss mice were inoculated with 500000 melanocytes B16F10 and given oral doses of diosmin, grape seed extract (GSE) and red wine...
  68. Sirlak M, Akar A, Eryilmaz S, Cetinkanat E, Ozcinar E, Kaya B, et al. Micronized purified flavonoid fraction in pretreating CABG patients. Tex Heart Inst J. 2010;37:172-7 pubmed
    ..Orally administered Daflon might provide better outcomes for patients who have impaired cardiac function before undergoing cardiac operations that require cardiopulmonary bypass. ..
  69. Bertozzi M, Rossaneis A, Fattori V, Longhi Balbinot D, Freitas A, Cunha F, et al. Diosmin reduces chronic constriction injury-induced neuropathic pain in mice. Chem Biol Interact. 2017;273:180-189 pubmed publisher
    ..The flavonoid diosmin is a safe compound with good tolerability and low toxicity...
  70. Pehlivan M, Hazinedaroglu S, Kayaoglu H, Erkek A, Keklik T, Canbolat O, et al. The effect of diosmin hesperidin on intestinal ischaemia--reperfusion injury. Acta Chir Belg. 2004;104:715-8 pubmed
    The effect of Diosmin Hesperidin on intestinal ischaemia reperfusion injury was evaluated in an experimental model in rats...
  71. Pokrovskii A, Sapelkin S. [Derivatives of semi-synthetic diosmine in the treatment of patients with chronic venous insufficiency. The results of a prospective study--using phlebodia 600]. Angiol Sosud Khir. 2005;11:73-9 pubmed
    ..The authors analyze the reports concerning the use of the above-indicated drug in European phlebological practice. ..
  72. Ma Y, Ma C. [Studies on pharmacokinetics of diosmin in rats]. Zhongguo Zhong Yao Za Zhi. 2007;32:418-20 pubmed
    To establish a HPLC method for the determination of diosmin in Rats plasma and to study the pharmacokinetics of diosmin in Rats. Rats were given diosmin with 3 doses as 225, 325, 425 mg x kg(-1)...
  73. Freag M, Elnaggar Y, Abdallah O. Development of novel polymer-stabilized diosmin nanosuspensions: in vitro appraisal and ex vivo permeation. Int J Pharm. 2013;454:462-71 pubmed publisher
    Scanty solubility and permeability of diosmin (DSN) are perpetrators for its poor oral absorption and high inter-subject variation...
  74. Raffetto J, Khalil R. Ca(2+)-dependent contraction by the saponoside escin in rat vena cava: implications in venotonic treatment of varicose veins. J Vasc Surg. 2011;54:489-96 pubmed publisher
    Saponosides (horse chestnut seed extract, escin) and flavonoids (diosmin, Daflon 500, Servier, France) exhibit venotonic properties that have been utilized in treatment of varicose veins...
  75. Tahir M, Rehman M, Lateef A, Khan A, Khan R, Qamar W, et al. Diosmin abrogates chemically induced hepatocarcinogenesis via alleviation of oxidative stress, hyperproliferative and inflammatory markers in murine model. Toxicol Lett. 2013;220:205-18 pubmed publisher
    ..In the present study, we have shown that diosmin attenuates 2-AAF induced hepatic toxicity and early tumor promotion markers (ODC, PCNA and Ki67), its ..
  76. Coleridge Smith P. From skin disorders to venous leg ulcers: pathophysiology and efficacy of Daflon 500 mg in ulcer healing. Angiology. 2003;54 Suppl 1:S45-50 pubmed
    ..There is clinical evidence that MPFF modifies venous leg ulcer healing. ..
  77. Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol. 2005;3:1-9 pubmed
    ..An explanation for the ability to speed ulcer healing comes from the protection Daflon 500 mg exerts on the microcirculation. ..
  78. Simsek M, Burak F, Taskin O. Effects of micronized purified flavonoid fraction (Daflon) on pelvic pain in women with laparoscopically diagnosed pelvic congestion syndrome: a randomized crossover trial. Clin Exp Obstet Gynecol. 2007;34:96-8 pubmed
    ..The mean scores were significantly less at the end of six months, respectively, p < 0.05. Pharmacologic enhancement of venous tonus may restore pelvic circulation and relieve pelvic symptomatology. ..
  79. Oganov R, Savel ev V, Shal nova S, Kirienko A, Zolotukhin I. [Risk factors of chronic venous insufficiency of the lower extremities and possibilities of its medication in therapeutic practice]. Ter Arkh. 2006;78:68-72 pubmed
    ..The effect was achieved in the detralex group. Many outpatients had symptoms of chronic venous insufficiency but had no complaints. Detralex therapy proved highly effective in outpatient practice. ..
  80. Veverkova L, Kalac J, Jedlicka V, Wechsler J. [Analysis of surgical procedures on the vena saphena magna in the Czech Republic and an effect of Detralex during its stripping]. Rozhl Chir. 2005;84:410-2, 414-6 pubmed
    ..High quality venoactive drugs administered 14 days prior to the surgery improve postoperative course in patients indicated for surgical treatment of varices. ..
  81. Zhou Y, Wang Y, Wang R, Guo F, Yan C. Two-dimensional liquid chromatography coupled with mass spectrometry for the analysis of Lobelia chinensis Lour. using an ESI/APCI multimode ion source. J Sep Sci. 2008;31:2388-94 pubmed publisher
    ..were detected and 6 of them were identified as apigenin 7-O-rutinoside, luteolin, lobetyolinin, lobetyolin, diosmin, and linarin, respectively, according to their UV spectrum and mass spectrum...
  82. Rajnarayana K, Venkatesham A, Nagulu M, Srinivas M, Krishna D. Influence of diosmin pretreatment on the pharmacokinetics of chlorzoxazone in healthy male volunteers. Drug Metabol Drug Interact. 2008;23:311-21 pubmed
    ..The second part of the study was conducted after a wash-out period of 7 days; 500 mg of diosmin (Venex 500) was administered daily for 9 days. On day 10, 250 mg of chlorzoxazone was administered...
  83. Sirotin B, Zhmerenetskĭ K. [Microcirculation end effect of detralex in patients with chronic venous insufficiency of the lower extremities]. Angiol Sosud Khir. 2003;9:60-5 pubmed
    ..Also, there was marked the lowering of intramuscular red blood cell aggregation. ..
  84. Mukherjee G, Gajaraj A, Mathias J, Marya D. Treatment of abnormal uterine bleeding with micronized flavonoids. Int J Gynaecol Obstet. 2005;89:156-7 pubmed
  85. Browning A, Walle U, Walle T. Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular uptake and hydrolysis to the aglycones. J Pharm Pharmacol. 2005;57:1037-42 pubmed
    ..b>Diosmin, the 7-rutinoside of diosmetin, surprisingly, was more potent and effective than diosmetin...
  86. Gongal skiĭ V, Prokopovich E. [Possibility of the regulation of venous outflow from deep brain structures]. Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105:62-3 pubmed
  87. Forte R, Cennamo G, Bonavolonta P, Pascotto A, de Crecchio G, Cennamo G. Long-term follow-up of oral administration of flavonoids, Centella asiatica and Melilotus, for diabetic cystoid macular edema without macular thickening. J Ocul Pharmacol Ther. 2013;29:733-7 pubmed publisher
    ..To evaluate long-term follow-up of the orally administered combination of flavonoids with Centella asiatica and Melilotus for treatment of diabetic cystoid macular edema (CME) without macular thickening...
  88. Korthuis R, Gute D. Adhesion molecule expression in postischemic microvascular dysfunction: activity of a micronized purified flavonoid fraction. J Vasc Res. 1999;36 Suppl 1:15-23 pubmed
    ..The micronized purified flavonoid fraction (450 mg diosmin, 50 mg hesperidin) prevents I/R-induced leukocyte adhesion in skeletal muscle...
  89. Araujo A, Araujo M, Swoboda K. Vascular perfusion abnormalities in infants with spinal muscular atrophy. J Pediatr. 2009;155:292-4 pubmed publisher
    ..Poor perfusion, autonomic dysfunction, and position-dependent factors may all play a role in the development of this complication. ..