Hesperidin methylchalcone
[CAS# 24292-52-2]

Identification

• Classification: Biochemical >> Antibody >> Immunity and inflammation
• Name: Hesperidin methylchalcone
• Synonyms: (E)-1-(4-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-hydroxy-6-methoxyphenyl)-3-(3-hydroxy-4-methoxyphenyl)-2-propen-1-one
• Molecular Formula: C₂₉H₃₆O₁₅
• Molecular Weight: 624.59
• CAS Registry Number: 24292-52-2
• EC Number: 246-128-2
• SMILES: 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(=C(C(=C3)OC)C(=O)/C=C/C4=CC(=C(C=C4)OC)O)O)O)O)O)O)O)O

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Melting point: 120 °°C (dec.) (Expl.)
• Boiling point: 953.0±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 309.5±27.8 °C (Calc.)^*
• Index of refraction: 1.672 (Calc.)^*
• Alpha: -71 ° (c=1 in ethanol) (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Hesperidin methylchalcone is a semisynthetic derivative of hesperidin, a naturally occurring flavonoid predominantly found in citrus fruits. It is formed by methylation and chalcone modification of the parent hesperidin molecule, which improves its solubility, bioavailability, and pharmacological activity. These chemical modifications enhance the compound's ability to exert biological effects while maintaining the structural features responsible for its therapeutic properties.

The discovery of hesperidin methylchalcone emerged from studies aimed at optimizing the efficacy of citrus flavonoids for vascular health. Hesperidin itself has been extensively studied for its antioxidant, anti-inflammatory, and venotonic effects. By introducing methyl and chalcone groups, researchers were able to improve the compound’s absorption in the gastrointestinal tract and increase its systemic bioavailability, which addressed the limitations of hesperidin’s relatively low oral bioavailability.

Hesperidin methylchalcone exhibits a broad spectrum of pharmacological activities, particularly in the cardiovascular system. It has been shown to strengthen venous tone, improve microcirculation, and reduce capillary permeability and fragility. These effects are beneficial in conditions such as chronic venous insufficiency, varicose veins, and hemorrhoidal disease. By enhancing venous return and reducing edema, the compound helps alleviate symptoms like heaviness, swelling, and discomfort in the lower limbs.

In addition to its vascular benefits, hesperidin methylchalcone demonstrates anti-inflammatory properties. It modulates inflammatory mediators, including cytokines and enzymes involved in inflammatory pathways, thereby reducing tissue inflammation and oxidative stress. Its antioxidant activity allows the compound to scavenge reactive oxygen species and protect endothelial cells from oxidative damage, which contributes to long-term vascular and cardiovascular health.

Pharmacokinetic studies suggest that methylation and chalcone modification enhance hesperidin methylchalcone’s solubility and metabolic stability, allowing it to maintain therapeutic plasma levels over extended periods. This property makes it suitable for oral administration and supports its use in pharmaceutical and nutraceutical formulations targeting vascular disorders.

Clinically, hesperidin methylchalcone is employed as a venotonic and microcirculation-supporting agent. It is commonly included in preparations for managing chronic venous insufficiency, varicose veins, and related inflammatory or circulatory conditions. The compound has been found to be well tolerated, with low incidence of adverse effects reported in preclinical and clinical evaluations, making it appropriate for long-term use.

Overall, hesperidin methylchalcone is a semisynthetic flavonoid derivative with enhanced pharmacological and pharmacokinetic properties compared to its parent compound hesperidin. Its venotonic, anti-inflammatory, antioxidant, and microcirculatory benefits make it a valuable therapeutic agent for vascular disorders. Continued research into its mechanisms of action and clinical applications is likely to expand its utility in both medicinal and nutraceutical contexts.

References

2025. Role of TRPV1+ and TRPA1+ nociceptive neurons in delayed-onset muscle soreness: inhibition by hesperidin methyl chalcone. Inflammopharmacology.
DOI: 10.1007/s10787-025-01762-6

2023. Hesperidin Methyl Chalcone reduces extracellular Aβ(25-35) peptide aggregation and fibrillation and also protects Neuro 2a cells from Aβ(25-35) induced neuronal dysfunction. Bioorganic & Medicinal Chemistry, 97.
DOI: 10.1016/j.bmc.2023.117536

2023. Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiO2 in Mice: Targeting Inflammation, Oxidative Stress, Cytokine Production, and Nociceptor Sensory Neuron Activation. Molecules (Basel, Switzerland), 28(2).
DOI: 10.3390/molecules28020872