Methyl hesperidin
[CAS# 11013-97-1]

Identification

• Classification: API >> Circulatory system medication >> Regulating blood lipids
• Name: Methyl hesperidin
• Synonyms: (2S)-2-(3,4-dimethoxyphenyl)-5-hydroxy-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]oxy-2,3-dihydrochromen-4-one
• Molecular Formula: C₂₉H₃₆O₁₅
• Molecular Weight: 624.59
• CAS Registry Number: 11013-97-1
• EC Number: 600-945-4
• 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(=C4C(=O)C[C@H](OC4=C3)C5=CC(=C(C=C5)OC)OC)O)O)O)O)O)O)O

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 900.4±65.0 ºC 760 mmHg (Calc.)^*
• Flash point: 293.0±27.8 ºC (Calc.)^*
• Index of refraction: 1.668 (Calc.)^*

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

Safety Data

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

Discovory and Applicatios

Methyl hesperidin is a flavonoid derivative of hesperidin, a naturally occurring bioflavonoid predominantly found in citrus fruits. Chemically, it is characterized as the 4′-O-methylated form of hesperidin, which enhances its lipophilicity and potential bioavailability compared to the parent compound. The compound has been recognized for its therapeutic properties and has been investigated in various pharmacological contexts.

The discovery of methyl hesperidin can be traced back to studies exploring citrus flavonoids and their derivatives. Researchers identified that methylation of the hydroxyl groups in hesperidin could modify its physicochemical properties, including solubility and metabolic stability. This structural modification aimed to improve the biological efficacy of the compound while maintaining the beneficial activities observed in natural hesperidin.

Methyl hesperidin has been explored for its antioxidant activity, which is one of the primary mechanisms underlying its therapeutic potential. The compound can scavenge reactive oxygen species and reduce oxidative stress, which is implicated in aging, cardiovascular diseases, and neurodegenerative conditions. Its antioxidant activity also contributes to anti-inflammatory effects by modulating pathways that regulate pro-inflammatory cytokines and enzymes. These properties suggest potential applications in preventing or mitigating chronic inflammatory diseases and oxidative stress-related conditions.

In addition to antioxidant and anti-inflammatory activities, methyl hesperidin has been studied for its cardiovascular protective effects. Experimental models have shown that it can improve endothelial function, enhance nitric oxide bioavailability, and modulate lipid metabolism. Such effects support its use as a dietary supplement or therapeutic agent in managing hyperlipidemia, hypertension, and other cardiovascular disorders. Methyl hesperidin's ability to influence blood lipid profiles and vascular tone further highlights its role as a bioactive flavonoid with potential preventive applications.

The metabolism and pharmacokinetics of methyl hesperidin differ from those of hesperidin due to the methylation. The modification generally increases resistance to enzymatic hydrolysis in the gastrointestinal tract, leading to improved systemic absorption. Studies indicate that methyl hesperidin can reach target tissues more efficiently and maintain therapeutic concentrations for longer durations, enhancing its overall efficacy.

In the field of nutraceuticals and functional foods, methyl hesperidin has gained attention as an ingredient that combines natural origin with improved pharmacological properties. It is incorporated into formulations aimed at supporting cardiovascular health, antioxidant defenses, and metabolic regulation. The compound is generally considered safe, with low toxicity observed in preclinical studies, although long-term clinical evaluations are limited.

Overall, methyl hesperidin represents a chemically modified flavonoid with enhanced bioavailability and a broad spectrum of pharmacological activities. Its antioxidant, anti-inflammatory, and cardiovascular protective effects make it a compound of interest in both research and applied health contexts. Continued studies on its mechanisms, bioavailability, and potential clinical applications will further define its role in promoting human health.

References

2022. Amentoflavone and methyl hesperidin, novel lead molecules targeting epitranscriptomic modulator in acute myeloid leukemia: in silico drug screening and molecular dynamics simulation approach. Journal of Molecular Modeling, 28(12).
DOI: 10.1007/s00894-022-05407-1

2019. Development of nobiletin-methyl hesperidin amorphous solid dispersion: Novel application of methyl hesperidin as an excipient for hot-melt extrusion. International Journal of Pharmaceutics, 559.
DOI: 10.1016/j.ijpharm.2018.12.092

2015. Hydrolyzed Methylhesperidin Induces Antioxidant Enzyme Expression via the Nrf2-ARE Pathway in Normal Human Epidermal Keratinocytes. Journal of Agricultural and Food Chemistry, 63(35).
DOI: 10.1021/acs.jafc.5b01992