Diosmin is a naturally occurring flavone glycoside used in the treatment of venous diseases. In this review, we present the clinical aspects of the use of diosmin preparations in venous stasis, hemorrheologic disorders and vein wall remodeling. Because of its multiple applications in biology and its many therapeutic activities, research on isolation and identification of diosmin is of high relevance. The aim of this review is to present an overview of techniques of isolation and separation of diosmin in plant material, pharmaceutical formulations such as Daflon®, Diosed® and Dioven® tablets, and biological fluids.
El-ShafaeAM, El-DomiatyMM. (2001) Improved LC methods for the determination of diosmin and/or hesperidin in plant extracts and pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 26, 539–545
2.
Londoño-LondoñoJ, Rodrigues de LimaV, LaraO, GilA, Crecsynski PasaTB, ArangoGJ, PinedaJRR. (2010) Clean recovery of antioxidant flavonoids from citrus peel: Optimizing an aqueous ultrasound-assisted extraction method. Food Chemistry, 119, 81–87
3.
SaeidiI, HadjmohammadiMR, PeyroviM, IranshahiM, BarfiB, BabaeiAB, DustAM. (2011) HPLC determination of hesperidin, diosmin and eriocitrin in Iranian lime juice using polyamide as an adsorbent for solid phase extraction. Journal of Pharmaceutical and Biomedical Analysis, 56, 419–422
4.
KanazeFI, BounartziMI, NiopasI. (2004) A validated HPLC determination of the flavone aglycone diosmetin in human plasma. Biomedical Chromatography, 18, 800–804
5.
KanazeFI, GabrieliC, KokkalouE, GeorgarakisM, NiopasI. (2003) Simultaneous reversed-phase high-performance liquid chromatographic method for the determination of diosmin, hesperidin and naringin in different citrus fruit juices and pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 33, 243–249
6.
CampaneroMA, EscolarM, PerezG, Garcia-QuetglasE, SadabaB, AzanzaJR. (2010) 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. Journal of Pharmaceutical and Biomedical Analysis, 51, 875–881
7.
JaneczkoZ, HubickaU, KrzekJ, PodolakI. (2003) Qualitative and quantitative analysis of diosmin in tablets by thin-layer chromatography with densitometric UV detection. Journal of Planar Chromatography, 16, 377–380
8.
ShawkyE. (2012) Development and validation of an HPTLC method for the simultaneous determination of diosmin and hesperidin in different citrus fruit extracts and pharmaceutical formulations. Journal of Planar Chromatography – Modern TLC, 25/2, 138–144
9.
DugoP, PrestiML, OhmanM, FazioA, DugoG, MondelloL. (2005) Detemination of flavonoids in citrus fruits juices by micro-HPLC-ESI/Ms. Journal of Separation Science, 28, 1149–1156
10.
SpanakisM, KasmasS, NiopasI. (2009) Simultaneous determination of the flavonoid aglycones diosmetin and hesperetin in human plasma and urine by a validated GC/MS method: in vivo metabolic reduction of diosmetin to hesperetin. Biomedical Chromatography, 23, 124–131.
11.
BatchvarovIV, BatselovaMG, DamyanovII. (2010) One-year diosmin therapy (600 mg) in patiens with chronic venous insufficiency – results and analysis. Journal of Biomedical and Clinical Research, 3/1, 51–54
12.
BoccalonH, SalvadoriC, BenedittiniD, SteruD, VilainC. (1996) Therapeutic equivalence of two dosage forms of a micronized flavonoid fraction in patients with chronic venous insufficiency. Current Therapeutic Research, 57, 757–766
13.
Lyseng-WilliamsonKA, PerryCM. (2003) Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs, 63, 71–100
14.
ShoabSS, ScurrJH, Coleridge-SmithPD. (1999) Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction - a pilot study. European Journal of Vasccular and Endovascular Surgery, 18/4, 334–338
15.
BerganJJ, Schmid-SchönbeinGW, SmithPD, NicolaidesAN, BoisseauMR, EklofB. (2006) Chronic venous disease. The New England Journal of Medicine, 355, 488–498
16.
ShoabSS, PorterJB, ScurrJH, Coleridge-SmithPD. (2000) Effect of oral micronized purified flavonoid fraction treatment on leukocyte adhesion molecule expression in patients with chronic venous disease: a pilot study. Journal of Vascular Surgery, 31/3, 456–461.
17.
Monographs. (2004) Diosmin. Alternative Medicine Review, 9/3, 308–311.
18.
IvashevMN, AndreevaOA, BandyukovaVA, DragalevaTD. (1995) Isolation of diosmin from plants of the genus Vicia and Hyssopus officinalis and its influence on blood coagulation. Pharmaceutical Chemistry Journal, 29/10, 707–709.
19.
SilambarasanT, RajaB. (2012) Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats. European Journal of Pharmacology, 679, 81–89.
20.
DholakiyaSL, BenzeroualKE. (2011) Protective effect of diosmin on LPS-induced apoptosis in PC12 cells and inhibition of TNF-a expression. Toxicology in Vitro, 25, 1039–1044.
21.
SrinivasanS, PariL. (2012) Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chemico-Biological Interactions, 195/1, 43–51.
22.
GlinskiW, ChodynickaB, RoszkiewiczJ, BogdanowskiT, Lacewicz-ToruńB, KaszubaA, BowszycJ, NowakA, WnorowskiJ, WšsikF, Glińska-FerenzM, BłaszczykM, StrzygaP, PachockiR. (1999) The beneficial augmentative effect of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: an open, multicenter, controlled, randomized study. Phlebology, 14, 151–157.
23.
CovaD, De AngelisL, GiavariniF, PalladiniG, PeregoR. (1992) Pharmacokinetics and metabolism of oral diosmin in healthy volunteers. International Journal of Clinical Pharmacology, Therapy and Toxicology, 30, 29–33.
24.
European Pharmacopoeia 5.0 (2005) Monographs D-E. Diosmin. Council of Europe, Strasbourg, 1452–1453.
25.
MoldovanZ, Aboul-EneinHY. (2011) A sensitive spectrophotometric method for determination of diosmin using sodium nitroprusside as a chromogenic reagent. Instrumentation Science and Technology, 39/2, 135–148
26.
BunaciuAA, UdristioiuGE, RutaLL, FleschinS, Aboul-EneinHY. (2009) Determination of diosmin in pharmaceutical formulations using Fourier transform infrared spectrophotometry. Saudi Pharmaceutical Journal, 17, 303–306
27.
MoldovanZ, BunaciuAA, Al-OmarMA, Aboul-EneinHY. (2010) A spectrophotometric method for diosmin determination. The Open Chemical and Biomedical Methods Journal, 3, 123–127.
28.
El-ShahawiMS, BashammakhAS, El-MogyT. (2006) Determination of trace levels of diosmin in a pharmaceutical preparation by adsorptive stripping voltammetry at a glassy carbon electrode. Analytical Sciences, 22, 1351–1354
29.
HanuštiakP, MikelováR, PotéšilD, HodekP, SiborovàM, KizekR. (2005) Electrochemical behaviour of flavonoids on a surface of a carbon paste electrode. Biomedical Papers (Supplement 1), 149, 44–47
30.
AdamV, MikelovaR, HubalekJ, HanustiakP, BeklovaM, HodekP, HornaA, TrnkovaL, StiborovaM, ZemanL, KizekR. (2007) Utilizing of square wave voltammetry to detect flavonoids in the presence of human urine. Sensors, 7, 2402–2418.
31.
TsymonianisEC, FlorasG, AntoniouN, PapanikolaouN, SiakasRTassisA. (1996) Low- molecular-weight heparins and Daflon for prevention of postoperative thrombo- embolism. World Journal of Surgery, 20, 968–972
32.
LabridC. (1987) Proprietes pharmacologiques de Daflon 500 mg. Journal of Internal Medicine, 85 (suppl), 30–36
33.
TsouderosY. (1992) Efficacy of Daflon 500 mg in the treatment of chronic venous insufficiency. Phlebology, 7 (suppl 2), 45–52
34.
LaurentR, GillyR, FrileuxC. (1988) Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg. International Angiology: a Journal of the International Union of Angiology, 7 (suppl 2), 39–43
35.
DuhaultJ, PillonG. (1992) Mecanisme d'action de Daflon 500 mg sur le tonus veineux noradrenergique. Arteres Veines, 11, 217–218
36.
GargouilYM. (1989) Effects of Daflon 500 mg on bovine vessel contractility. International Journal of Angiology, 8 (suppl 4), 19–22
37.
CotonatA. (1989) Lymphagogue and pulsatile activities of Daflon 500 mg on canine thoracic lumph duct. International Journal of Angiology, 8 (suppl 4), 15–18
38.
BouskelaE, DonyoKA, VerbeurenTJ. (1995) Effects of Daflon 500 mg on increased microvascular permeability in normal hamsters. International Journal of Microcirculation: Clinical and Experimental, 15 (Suppl. 1), 22–26
39.
PascarellaL, LulicD, PennAH, AlsaighT, LeeJ, ShinH, KapurV, BerganJJ, Schmid-SchönbeinGW. (2008) Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg. European Journal of Vascular and Endovascular Surgery, 35/1, 102–110
40.
Boisneau-GeniauxD. (1988) Activite thérepeutique de Daflon 500 mg sur les troubles trophiques de l'insuffisance veineuse. Angiologie, 5 (suppl 73), 20–23
41.
LacombeC, BuchererC, LelevrieJC. (1988) Hemorheological improvement after Daflon 500 mg treatment in diabetes. International Angiology, 7 (suppl 2), 21–24
42.
StuekerO. (1989) Daflon 500 mg depresses bradykinin-ischemia-induced microvascular leakage of FITC Dextran in rat cremaster muscle. International Angiology, 8 (suppl 4), 39–44
43.
McHaleNG, HollywoodMA. (1994) Control of lymphatic pumping: interest of Daflon 500 mg. Phlebology, (suppl 1), 23–25
44.
BlumeJ, LangehbahnH, de ChampvallinsM. (1992) Quantification of edema using the volumeter technique: therapeutic application of Daflon 500 mg in chronic venous insufficiency. Phlebology, 7 (suppl 2), 37–40
45.
GuilhouJJ, DereureO, MarzinL, OuvryP, ZuccarelliF, DebureC, Van LanduytH, Gillet-TerverMN, GuillotB, LevesqueH, MiqnotJ, PillionG, FévrierB, DubeauxD. (1997) Efficacy of Daflon 500 mg in venous leg ulcer healing: A double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology, 48/1, 77–85.
46.
BujanJ, Jimenez-CossioJA, JuradoF, GimenoMJ, PascualG, Garcia-HonduvillaN, DominguezB, BellonJM. (2000) Evaluation of the smooth muscle cell component and apoptosis in the varicose vein wall. Histology and Histopathology, 15, 745–752
47.
KowalewskiR, GńowihskiS, SobolewskiK, WolańskaM, PłońskiA. (2000) Przebudowa macierzy miȩdzykomórkowej w ścianie żylaków. Polski Przeglqd Chirurgiczny (in Polish), 72, 912–920
48.
Badier-CommanderC, CouvelardA, HeninD, VerbeurenT, MichelJB, JacobMP. (2001) Smooth muscle cell modulation and cytokine overproduction in varicose veins. An in situ study. The Journal of Pathology, 193/3, 398–407
49.
KowalewskiR, MalkowskiA, SobolewskiK, GackoM. (2009) Evaluation of aFGF/bFGF and FGF signaling pathway in the wall of varicose veins. Journal of Surgical Research, 155/1, 165–172.
50.
NarayanaKR, ReddyMS, ChaluvadiMR, KrishnaDR. (2001) Bioflavonoids classification, oharmacological, biochemical effects and therapeutic potential. Indian Journal of Pharmacology, 33, 2–16
51.
HerreraMD, ZarzueloA, JiménezJ, MarhuendaE, DuarteJ. (1996) Effects of flavonoids on rat aortic smooth muscle contractility: structure - activity relationships. General Pharmacology, 27/2, 273–277.
52.
PascarellaL, Schmid-SchönbeinGW, BerganJ. (2005) An animal model of venous hypertension: the role of inflammation in venous valve failure. Journal of Vascular Surgery, 41/2, 303–311
53.
TakaseS, LerondL, BerganJJ, Schmid-SchönbeinGW. (2000) The inflammatory reaction during venous hypertension in the rat. Microcirculation, 7/1, 41–52.
54.
CyrinoFZ, BottinoDA, LerondL, BouskelaE. (2004) Micronization enhances the protective effect of purified flavonoid fraction against postischaemic microvascular injury in the hamster cheek pouch. Clinical and Experimental Pharmacology & Physiology, 31/3, 159–162.
55.
MiaoH, HuYL, ShiuYT, YuanS, ZhaoY, KaunasR, WangY, JinG, UsamiS, ChienS. (2005) Effects of flow patterns on the localization and expression of VE- cadherin at vascular endothelial cell junctions: in vivo and in vitro investigations. Journal of Vascular Research, 42/1, 77–89.
56.
Garcia-CardenaG, ComanderJ, AndersonKR, BlackmanBR, GimboreMAJr. (2001) Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proceedings of the National Academy of Sciences USA, 98/8, 4478–4485.
