Aryl hydrocarbon receptor (AhR) [1]

Adduct formation increased in response to diosmin treatment in a dose-dependent manner (adduct formation increased up to 7-fold at 5 μM diosmin). The cytotoxicity of 7,12-dimethylbenzo(a)anthracene is increased by diosmin at 5 μM, resulting in a change in the IC50 from an estimated 1.2 μM to 400 nM. At the studied concentrations, diosmin is not cytotoxic in and of itself. In MCF-7 cells, diosmin increased CYPIAI activity in a dose- and time-dependent manner. After 24 hours of incubation, diosmin generates a dose-dependent rise in CYPIAI mRNA, which results in a persistent increase in CYPIAI mRNA accumulation that peaks after 48 hours of incubation [1].

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- Effect on carcinogen activation pathway: In MCF - 7 human breast epithelial cancer cells, treatment with Diosmin led to a dose - dependent increase in the metabolism of the mammary carcinogen 7,12 - dimethylbenz(a)anthracene (DMBA). This was evaluated by an increase in the formation of DMBA - DNA adducts and DMBA - induced cytotoxicity. Diosmin also caused a dose - and time - dependent increase in cytochrome P450 1A1 (CYP1A1) activity in intact cells, comparable to that induced by DMBA or the aryl hydrocarbon benzo(a)pyrene. It increased the transcription of the CYP1A1 gene, as measured by elevated levels of CYP1A1 mRNA and activated the DNA - binding capacity of the AhR for the xenobiotic - responsive element of CYP1A1 [1]

- Protection against retina ischemia/reperfusion injury: In a rat model of retina ischemia/reperfusion injury, Diosmin protected the rat retina. It reduced the levels of malondialdehyde (MDA), a marker of oxidative stress, and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), which are antioxidant enzymes. It also decreased the expression of caspase - 3, a key enzyme in apoptosis, and reduced the number of TUNEL - positive apoptotic cells in the retina [2]

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In the rat retina, diosmin markedly boosted glutathione peroxidase (GSH) and total superoxide dismutase (T-SOD) levels and dramatically decreased malondialdehyde (MDA) levels as compared to the ischemia group. P<0.05), catalase (CAT) activity, and the reduction in electroretinogram (ERG) a- and b-wave amplitude brought on by ischemia/reperfusion (I/R) were all suppressed. The entire retina's thickness, the inner nuclear layer, the inner plexiform layer, the outer retinal layer, and the quantity of cells in the ganglion cell layer all considerably decreased (P<0.05) following I/R injury, and diosin significantly improved these alterations. shape of the retina. In the rat retina, diosmin can also lessen the loss of retinal ganglion cells (RGC) brought on by I/R (P<0.05)[2].

CYP1A1 activity assay: Microsomes were isolated from DMBA - treated MCF - 7 cells. The activity of CYP1A1 was assayed by ethoxyresorufin - O - deethylase activity. Treatment of intact MCF - 7 cells with Diosmin led to an increase in CYP1A1 activity in a dose - and time - dependent manner. However, Diosmin did not directly inhibit CYP1A1 activity in microsomes, in contrast to its aglycone form diosmetin [1]

- Carcinogen metabolism and CYP1A1 - related assays in MCF - 7 cells: MCF - 7 human breast epithelial cancer cells were treated with different concentrations of Diosmin. To assess the metabolism of DMBA, the formation of DMBA - DNA adducts was measured using appropriate techniques. The cytotoxicity induced by DMBA was evaluated by methods such as MTT assay. For CYP1A1 activity, the cells were incubated with Diosmin for various time periods, and then the activity of CYP1A1 in intact cells was determined. The levels of CYP1A1 mRNA were measured by quantitative polymerase chain reaction (qPCR) to assess the transcriptional regulation of the CYP1A1 gene [1]
- Oxidative stress and apoptosis - related assays in retinal cells: In an in vitro model of retina ischemia/reperfusion injury using retinal cells, the cells were treated with Diosmin. The levels of MDA were measured using a colorimetric assay kit. The activities of SOD and GPx were determined using specific enzymatic assay kits. The expression of caspase - 3 was analyzed by western blot, and the number of apoptotic cells was detected by TUNEL assay [2]

Retina ischemia/reperfusion injury model: Rats were anesthetized. Retina ischemia was induced by increasing the intraocular pressure. After a certain period of ischemia, the intraocular pressure was released to allow reperfusion. Diosmin was dissolved in an appropriate vehicle (not specified in detail in the literature) and administered to rats by intragastric gavage at a certain dose (not clearly given in the literature) once a day for a specific number of days (not clearly stated in the literature). After the treatment period, the rats were sacrificed, and the retinas were collected for further analysis, including measurement of MDA, SOD, GPx, caspase - 3, and TUNEL assay [2]

Absorption, Distribution and Excretion
Diosmin is rapidly absorbed in the gastrointestinal tract. A study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that after a single oral dose of 900 mg diosmin in healthy volunteers, the Cmax was 4.2 ± 3.8 ng·mL⁻¹, the Tmax was 18.7 ± 9.9 hours, and the AUC0–96 was 185.4 ± 166.2 ng·mL⁻¹. Another pharmacokinetic study in 5 adults showed a Cmax of 417 ± 94.1 ng/dL. Pharmacokinetic data indicate that diosmin and its aglycone diosmin are not excreted in the urine. Secondary metabolites are excreted in the urine as glucuronide conjugates. A pharmacokinetic study in 5 adults showed a volume of distribution of 62.1 ± 7.9 L. Metabolites/Metabolites: Degradation products of diosmin, such as alkylphenolic acids, confirm that its metabolic pattern is similar to that of other flavonoids. Biological Half-Life: The half-life of diosmin is 26 to 43 hours. A study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that the half-life of diosmin after a single dose of 900 mg in healthy volunteers was 60.2 ± 85.7 hours.

Protein Binding
Diosmin binds to serum albumin.

[1]. Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affectcytochrome P450 1A1 activity. Cancer Res. 1998 Jul 1;58(13):2754-60.

[2]. Diosmin protects rat retina from ischemia/reperfusion injury. J Ocul Pharmacol Ther. 2012 Oct;28(5):459-66.

Diosmin is a flavonoid glycoside. Its effects on the aryl hydrocarbon receptor (AhR)-mediated carcinogen activation pathway in cancer cells and its protective effect against retinal ischemia/reperfusion injury have been studied. It is a natural dietary agonist of AhR and can increase the transcription and activity of CYP1A1, thereby potentially affecting the metabolism of carcinogens. In terms of retinal ischemia/reperfusion injury, it exerts a protective effect through antioxidant and anti-apoptotic mechanisms [1][2]. Diosmin is a disaccharide derivative formed by replacing diosmin at the 7-position with 6-O-(α-L-rhamnosyl)-β-D-glucopyranosyl via a glycosidic bond. It has antioxidant and anti-inflammatory effects. It is a glycosyloxyflavonoid, rutin, disaccharide derivative, monomethoxyflavonoid, and dihydroxyflavanone. Its function is related to diosmin. Chronic venous insufficiency is common in Western populations. Compression therapy and pharmacological therapy are commonly used to treat chronic venous insufficiency, improve blood circulation, and alleviate symptoms of venous disease. Diosmin is a bioflavonoid isolated from various plants or synthesized from hesperidin. It is used to improve capillary fragility or venous insufficiency, including chronic venous insufficiency (CVI) and hemorrhoids. Diosmin is a widely used over-the-counter drug with a good safety profile. It has been reported to be found in Angelica sinensis, Abies repens, and several other organisms with relevant data. It is a bioflavonoid that strengthens blood vessel walls. See also: Birch leaf (partial). Drug Indications Diosmin can be used alone or in combination with other ingredients such as hesperidin and diosmin to support venous and capillary function. Mechanism of Action Diosmin helps maintain the structure and function of the circulatory system, particularly the strength and patency of veins. The molecular mechanism of action of diosmin is not yet fully understood. Some studies suggest that diosmin binds to aryl hydrocarbon receptors, but its clinical significance for vascular function remains unclear. A study suggests that oral diosmin can affect the in vitro metabolism of norepinephrine in varicose vein cells, potentially benefiting vascular health.

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Pharmacodynamics
Diosmin is a venously active drug that supports circulatory health through multiple effects on blood vessels; it promotes lymphatic drainage, improves microcirculation, and enhances venous tone and elasticity. Therefore, patients with chronic venous disease often take diosmin to support vascular health and it has been shown to improve quality of life. In addition to the above effects, diosmin also has antioxidant activity, scavenging oxygen free radicals and reducing oxidative stress levels typically detected by biomarkers such as prostaglandins and isoprostane precursors. In a clinical study, diosmin treatment reduced the average levels of TNF-α, VEGF-C, VEGF-A, IL-6, and FGF2; these results were statistically significant. Furthermore, a clinical study observed a reduction in edema and average leg circumference in patients taking diosmin for three months. Diosmin has also been shown to enhance glucose metabolism in diabetic patients.

C28H32O15

608.54

608.174

C, 55.26; H, 5.30; O, 39.44

520-27-4

5281613

Light yellow to light brown solid powder

1.7±0.1 g/cm3

926.8±65.0 °C at 760 mmHg

277-278°C

305.2±27.8 °C

0.0±0.3 mmHg at 25°C

1.712

2.05

8

15

7

43

995

10

C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)OC[C@@H]2[C@H]([C@@H]([C@H]([C@@H](O2)OC3=CC(=C4C(=C3)OC(=CC4=O)C5=CC(=C(C=C5)OC)O)O)O)O)O)O)O)O

GZSOSUNBTXMUFQ-YFAPSIMESA-N

InChI=1S/C28H32O15/c1-10-21(32)23(34)25(36)27(40-10)39-9-19-22(33)24(35)26(37)28(43-19)41-12-6-14(30)20-15(31)8-17(42-18(20)7-12)11-3-4-16(38-2)13(29)5-11/h3-8,10,19,21-30,32-37H,9H2,1-2H3/t10-,19+,21-,22+,23+,24-,25+,26+,27+,28+/m0/s1

5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one

diosmin; 520-27-4; Barosmin; Diosmine; Venosmine; Flebosten; Tovene; Ven-Detrex;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~164.33 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (4.11 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)