Synonym name: Barosmin; Diosmetin-7-O-rutinoside
Catalogue No.: BP0508
Cas No.: 520-27-4
Formula: C₂₈H₃₂O₁₅
Mol Weight: 608.549


Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

We provide the impurities of Diosmin, including the follow compounds:

• 6-Iodo Diosmin(Impurity D)
  1431536-92-3
• Acaciin(Impurity E)
  480-36-4
• Diosmetin(Impurity F)
  520-34-3
• Diosmin
  520-27-4
• Didymin
  14259-47-3
• Hesperetin(Impurity G)
  520-33-2
• Hesperidin(Impurity B)
  520-26-3
• Isorhoifolin(Impurity C)
  552-57-8
• Isoacetovanillone(Impurity A)
  6100-74-9
• Narirutin
  14259-46-2

HPLC of Diosmin

HNMR of Diosmin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Diosmin (CAS No.: 520-27-4) is a flavonoid compound naturally found in citrus fruits, classified as a flavonoid disaccharide derivative. As a functional bioactive molecule, Diosmin demonstrates broad application potential in the prevention and treatment of vascular-related diseases such as venous insufficiency due to its remarkable antioxidant and anti-inflammatory properties. In recent years, with in-depth research into its molecular mechanisms, diosmine has been found to exert pharmacological effects by regulating various inflammatory and vascular homeostasis-related targets, especially its function as an aromatic hydrocarbon receptor (AhR) agonist, providing new perspectives on its mechanism of action in vascular pathology.

This review aims to systematically summarize the chemical structure and physicochemical properties of diosmin, plant origin and extraction methods, pharmacological activity and mechanism of action, efficacy evaluation and pharmacokinetic characteristics, as well as its prospects and development directions in clinical application, aiming to provide comprehensive and in-depth reference materials for researchers in the field of natural product pharmacology.

Chemical structure and physicochemical properties

Diosmine is a flavonoid disaccharide derivative whose chemical structure is based on the Diosmetin backbone, with a glycosidic bond at position 7 linked to the 6-O-(α-L-rhamnosid group)-β-D-pyranglucose group. Its molecular weight is 608.5490, and its molecular formula is C_28H_32O_15. Diosmin's structure contains functional groups such as monomethoxyflavonoids, rutin, and dihydroxyflavones, endowing it with multiple biological activities.

In terms of physicochemical properties, Diosmin's LogP value is about -0.0599, indicating strong hydrophilicity, water solubility of 2.6865, and a polar surface area (TPSA) of 238.2 Ų, indicating high polarity and good water solubility. Its blood-brain barrier penetration ability is relatively low, suggesting it mainly acts on the peripheral vascular system rather than the central nervous system. hERG channel inhibition assays showed that diosmine poses no significant cardiotoxicity risk, while Ames-induced mutagenic tests showed a value of 0.6, indicating low genotoxicity and good safety.

Plant Origins and Extraction Methods

Diosmin is mainly found in the peel and fruit of citrus plants, especially bitter orange (Citrus aurantium), sweet orange (Citrus sinensis), and pomelo (Citrus paradisi). Its content is greatly influenced by variety, maturity, and growing environment. Traditionally, the extraction of Diosmin has relied on organic solvent extraction and separation purification technologies.

Common extraction methods include:

1. Solvent extraction involves extracting citrus peels using ethanol, water, or a mixture of solvents, combined with ultrasound assistance to improve extraction efficiency.
2. Liquid-liquid distribution: Disperses by distributing solvents of different polarities to remove impurities and enrich the diasmine component.
3. Chromatographic separation: Purifying the extract using high-performance liquid chromatography (HPLC) or reversed-phase column chromatography to obtain high-purity diaosmine.
4. Enzymatic hydrolysis: For flavonoid glycoside structures, specific enzymatic hydrolysis can be used to partially hydrolyze glycosides, further analyzing and utilizing diosmine and its derivatives.

In recent years, green extraction technologies such as supercritical CO_2 extraction and microwave-assisted extraction have also been attempted to extract Diosmin to improve yield and purity while reducing environmental pollution.

Pharmacological activity research

The pharmacological activity of diosmine is mainly reflected in its antioxidant, anti-inflammatory, and vascular-protective effects, especially in the treatment of venous insufficiency and related vascular diseases.

Antioxidant effects

Diosmin can effectively eliminate free radicals, inhibit lipid peroxidation, and protect cell membranes and vascular endothelial cells from oxidative damage. Its antioxidant mechanism involves activating endogenous antioxidant enzyme systems, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), which lowers reactive oxygen species (ROS) levels and thereby alleviates cellular damage caused by oxidative stress.

Anti-inflammatory effects

Diosmine exerts significant anti-inflammatory effects by inhibiting the release of inflammatory mediators and activating inflammatory signaling pathways. Research shows that diosmine can downregulate the expression of pro-inflammatory cytokines (such as TNF-α, IL-1β, IL-6) and adhesion molecules (ICAM-1, VCAM-1, SELE), reducing vascular wall inflammatory responses and improving vascular permeability and blood circulation.

Vascular protection

Dioximin is especially important in the treatment of venous insufficiency. By regulating vasomotor and contractile functions, inhibiting matrix metalloproteinases (MMP2, MMP9) activity, promoting collagen synthesis (COL1A1, COL3A1), and enhancing vascular wall structural integrity. At the same time, Diosmin can also promote nitric oxide synthase (NOS3) activity, increase nitric oxide (NO) release, improve vasodilatory function, and reduce venous pressure and vascular stagnation.

Additionally, Diosmin's regulation of the vascular endothelial cell adhesion molecule PECAM1 helps reduce leukocyte adhesion and inflammatory exudation, further protecting vascular function.

Mechanism of action and molecular targets

The mechanism of action of diasmine is complex, involving multiple signaling pathways and molecular targets, mainly including:

Effects of aromatic hydrocarbon receptor (AhR) agonists

As an agonist of aromatic hydrocarbon receptors, diosmine can regulate intracellular transcriptional activity, affecting inflammatory responses and cellular metabolism. After activation, AhR can regulate the expression of various genes, participate in immune regulation and detoxification processes, and thereby exert anti-inflammatory and antioxidant effects.

Matrix metalloproteinases (MMP2, MMP9)

MMPs play a key role in vascular remodeling and inflammation. Diosmine reduces collagen degradation by inhibiting the expression and activity of MMP2 and MMP9, maintains the integrity of the vascular basement membrane, and prevents structural damage to the vessel wall.

angiotensin-converting enzyme (ACE)

ACE is an important enzyme that regulates vasoconstriction and blood pressure. Diosmin partially inhibits ACE activity, helps lower angiotensin II levels, alleviates vasoconstriction, and improves venous function.

Nitric oxide synthase (NOS3)

Diosmin promotes the activity of endothelial nitric oxide synthase (eNOS, NOS3), increases NO production, dilates blood vessels, improves hemodynamics, and reduces pressure on vessel walls.

Adhesion molecules (ICAM1, VCAM1, SELE, PECAM1)

Diosmin downregulates the expression of adhesion molecules on the surface of vascular endothelial cells, inhibits the adhesion and penetration of white blood cells to the vessel wall, reduces inflammatory responses, and protects vascular endothelial function.

Collagen (COL1A1, COL3A1)

By regulating collagen synthesis and degradation, Diosmine enhances the mechanical strength and elasticity of blood vessel walls, preventing varicose veins and vasodilation.

Druggability evaluation and pharmacokinetics

The druggability parameters of Diosmin indicate good safety and potential clinical value.

Physicochemical properties and pharmacokinetics

• Molecular weight: 608.5490; a larger molecular weight may affect oral absorption.
• LogP: -0.0599, indicating that Diosmin is highly hydrophilic and facilitates dissolution in the blood.
• TPSA: 238.2 Ų. Its higher polarity may limit membrane permeability, but it is beneficial for water solubility and distribution.
• Water solubility: 2.6865, indicating good solubility in water.
• Blood-brain barrier penetration: low, indicating it mainly acts on peripheral tissues, reducing the risk of central nervous system side effects.

Safety evaluation

• hERG channel inhibition: no significant inhibition, low risk of cardiotoxicity.
• Ames mutagenic test: 0.6, low genotoxicity, relatively high safety.

Pharmacokinetic characteristics

After oral administration, Diosmine is mainly hydrolyzed in the intestines into its active ingredient, aromatin, which is then absorbed into the bloodstream. Its bioavailability is limited by the hydrolysis efficiency of glycoside structures and gut microbial metabolism. Dioximin and its metabolites are mainly metabolized by the liver, with some excreted by the kidneys. Its half-life is moderate, making it suitable for daily medication.

Prospects and outlooks for clinical applications

As a safe and effective natural product, Dioximin has been widely used in the treatment of venous insufficiency, hemorrhoids, chronic venous diseases, and related inflammatory vascular lesions. Through multi-target and multi-mechanism synergistic effects, it improves the structure and function of blood vessel walls, reduces inflammation and oxidative stress, significantly alleviates symptoms, and enhances patients' quality of life.

In the future, the clinical application prospects of Dioximin will mainly be reflected in the following aspects:

1. Combination therapy strategy: combined with other vasoactive drugs and anti-inflammatory drugs to exert synergistic effects and improve treatment outcomes.
2. New dosage form development: Improving the bioavailability and targeting of Diosmin through nanocarriers, sustained-release formulations, and other technologies to enhance efficacy.
3. Indication expansion: Based on its anti-inflammatory and antioxidant properties, explore potential applications in diabetic vascular lesions, atherosclerosis, and neurovascular diseases.
4. In-depth research on molecular mechanisms: further elucidating the interactions between diosmine and aromatic hydrocarbon receptors and other signaling pathways to guide the design of precision therapy plans.
5. Individualized medication: Combining pharmacogenomics to optimize the dosage and regimen of diosmin, enhancing treatment safety and efficacy.

Conclusion

As a natural flavonoid dighanoid derivative, Diosmin demonstrates significant value in vascular protection and anti-inflammatory fields due to its unique chemical structure and multi-target pharmacological effects. Its excellent safety and druggability make it an ideal candidate for treating venous insufficiency and related diseases. In the future, by deepening research into its mechanisms of action and optimizing drug formulations, Diosumin is expected to realize greater potential in clinical treatment and promote the development and application of natural product pharmacology.

In summary, diosmine is not only an important active ingredient in citrus fruits but also a key molecule in the pharmacological research of natural products and the treatment of vascular diseases, worthy of ongoing attention and in-depth exploration.