Product name: 5,7,3',4'-Tetramethoxyflavone
Synonym name: Luteolin tetramethylether; Tetramethylluteolin;Tetramethoxyluteolin 
Catalogue No.: BP4209
Cas No.: 855-97-0
Formula: C₁₉H₁₈O₆
Mol Weight: 342.347
Botanical Source:
Type of Compound: Flavonoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of 5,7,3',4'-Tetramethoxyflavone

HNMR of 5,7,3',4'-Tetramethoxyflavone

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

Introduction/Overview

Oleander Tetramethoxyflavone (5,7,3 ', 4' - Tetramethoxyflavone, CAS number: 855-97-0) is a naturally occurring methoxylated flavonoid compound widely distributed in various Chinese medicinal herbs and plants. As a derivative of flavonoids, luteolin methyl ether has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and biological activity. Its significant antioxidant activity and interactions with multiple key molecular targets make it potentially valuable for the prevention and treatment of oxidative stress-related diseases. This article aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, and pharmacological evaluation of luteolin tetramethyl ether, and explore its potential clinical applications and development directions in the future.

Chemical structure and physicochemical properties

Osmanthus fragrans methyl ether belongs to the methoxy derivatives of flavonoids, and its chemical structure is based on the flavonoid skeleton, with four methoxy substituents at positions 5, 7, and 3 ', 4'. The molecular formula is C19H18O6 and the molecular weight is 342.3470. Its structural characteristics endow the molecule with unique physicochemical properties:

• hydrophobicity The LogP value is 2.9812, indicating moderate lipid solubility that facilitates its penetration through cell membranes and the blood-brain barrier.
• Polarized surface area (TPSA)67.13 Å ² indicates that its molecules have a certain polarity, which facilitates binding with biomolecules.
• Water solubility Extremely low (0.0028 mg/mL), indicating limited solubility in aqueous phase, which may affect its bioavailability.
• Blood-brain barrier penetration ability High indicates its potential central nervous system activity.
• safety indicator HERG channel inhibition is negative, and the Ames test result is 0.9, indicating a low risk of genetic toxicity and a good safety basis.

In summary, the physicochemical properties of luteolin tetramethyl ether demonstrate its good membrane permeability and safety in vivo, but its poor water solubility may limit its oral absorption and bioavailability, which needs to be improved through formulation optimization or structural modification.

Plant sources and extraction methods

Oleander methyl ether is mainly found in the genus Lonicera spp., flavonoids rich traditional Chinese medicinal materials, and certain aromatic plants. Common plant sources include:

• Osmanthus (Lonicera japonica)Traditional Chinese medicinal herbs contain abundant flavonoids.
• Honeysuckle (Lonicera macranthoides)Its flower buds contain various methoxyflavones.
• Other plants with high flavonoid content Like some Rutaceae plants.

The extraction method usually uses organic solvent extraction combined with chromatographic separation technology:

1. Solvent selection Methanol, ethanol, or ethyl acetate are commonly used as extraction solvents due to their good solubility in flavonoids.
2. extraction process Adopting reflux extraction, ultrasound assisted extraction, or microwave-assisted extraction to improve extraction efficiency.
3. Purification and Separation High purity luteolin tetramethyl ether was obtained through methods such as silica gel column chromatography and high-performance liquid chromatography (HPLC).
4. Structural Identification Confirm the structure of the compound using techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, green extraction techniques such as supercritical CO2 extraction and deep eutectic solvent assisted extraction have gradually been applied to the extraction of such compounds, aiming to improve extraction efficiency and reduce environmental pollution.

Pharmacological activity research

The pharmacological activity research of luteolin tetramethyl ether mainly focuses on its antioxidant effect, but its biological activity range is constantly expanding.

antioxidant activity

As a natural flavonoid methoxy derivative, luteolin tetramethyl ether exhibits significant free radical scavenging ability. In vitro experiments have shown that it can effectively scavenge DPPH radicals, superoxide anions, and hydroxyl radicals, and alleviate oxidative stress damage. Its antioxidant activity is closely related to the electron supply ability of multiple methoxy groups in its structure.

anti-inflammatory effect

Oxidative stress is closely related to inflammation, and luteolin tetramethyl ether indirectly inhibits the release of inflammatory mediators by regulating the redox state. Some studies have shown that it can inhibit the expression of inflammatory factors such as TNF - α and IL-6, and alleviate inflammatory reactions.

Cellular protective effect

In various cell models, luteolin tetramethyl ether enhances intracellular antioxidant enzyme activity, protects cells from oxidative damage, and promotes cell survival. Its protective effect on nerve cells and myocardial cells is particularly significant, indicating its potential applications in neurodegenerative diseases and cardiovascular diseases.

Other activities

Preliminary studies have also found that luteolin tetramethyl ether has certain anti-tumor activity, which can inhibit tumor cell proliferation by regulating the cell cycle and inducing apoptosis. In addition, its regulatory effect on certain enzyme activities also provides a basis for its multi-target pharmacological mechanism.

Mechanism of action and molecular targets

The biological activity of luteolin tetramethyl ether is closely related to its regulation of various key molecular targets, especially in the antioxidant pathway where its mechanism of action is relatively clear.

Antioxidant related targets

• Tyrosinase (TYR)Osmanthus fragrans methyl ether may affect melanin synthesis and redox balance by regulating TYR activity.
• Matrix metalloproteinases 1 and 3 (MMP1, MMP3)By inhibiting the overexpression of MMPs, reducing tissue matrix degradation, and protecting extracellular matrix stability.
• NFE2L2/NRF2 signaling pathway As the main intracellular antioxidant transcription factor, NRF2 regulates the expression of various antioxidant enzyme genes. Oleander methyl ether can activate NRF2, promote the expression of downstream antioxidant enzymes such as SOD1, SOD2, CAT, GPX1, and HMOX1, and enhance cellular antioxidant defense ability.
• Superoxide dismutase (SOD1, SOD2)、Catalase (CAT)、Glutathione peroxidase 1 (GPX1)and Heme Oxygenase 1 (HMOX1)These enzymes are the main antioxidant enzymes in cells, and luteolin tetramethyl ether enhances their activity, reduces reactive oxygen species (ROS) levels, and alleviates oxidative damage.

Other potential targets and mechanisms

In addition to the antioxidant pathway, luteolin tetramethyl ether may also exert anti-inflammatory and cell protective effects by regulating cellular signaling pathways such as NF - κ B and MAPK. In addition, its methoxy structure may affect its binding affinity with enzyme proteins, regulate enzyme activity, and gene expression.

Evaluation of drug properties and pharmacokinetics

The pharmacological analysis of luteolin tetramethyl ether is based on its physicochemical properties and in vivo behavior, and its potential as a candidate drug is comprehensively evaluated.

Absorption and distribution

• Moderate lipid solubility(LogP is about 2.98), which is beneficial for oral absorption and cell membrane penetration.
• High blood-brain barrier permeability It suggests that it can be used for the treatment of central nervous system diseases.
• Low water solubility It is the main limiting factor for its absorption, which may lead to a decrease in bioavailability.

Metabolism and excretion

At present, there is limited research on the metabolic pathway of luteolin tetramethyl ether, and it is speculated that it may be metabolized by the liver cytochrome P450 enzyme system, producing metabolites such as methoxydemethylation. The activity and toxicity of metabolites need further evaluation.

safety

• HERG channel inhibition negative Reduce the risk of cardiac toxicity.
• The Ames test result is 0.9 Indicating no significant genetic toxicity.
• In vivo toxicology research still needs to be systematically conducted to comprehensively evaluate its safety.

Pharmacokinetic challenges and strategies

The low water solubility limits its oral bioavailability, and in the future, its solubility and absorption can be improved through technologies such as nano formulations, liposome encapsulation, and solid dispersions. Meanwhile, structural modification to enhance polarity or introduce hydrophilic groups is also an effective strategy to improve its pharmacokinetic performance.

Clinical application prospects and prospects

Based on the significant antioxidant and cell protective effects of luteolin tetramethyl ether, it has potential clinical application value in various oxidative stress-related diseases:

• Neurodegenerative diseases For diseases such as Alzheimer's and Parkinson's, luteolin tetramethyl ether reduces neuronal oxidative damage and protects neural function by activating the NRF2 pathway.
• cardiovascular disease Its antioxidant and anti-inflammatory effects help prevent atherosclerosis and myocardial ischemia-reperfusion injury.
• Skin diseases and beauty field By inhibiting tyrosinase activity and antioxidant mechanisms, luteolin tetramethyl ether can be used to prevent and treat skin aging and pigmentation.
• neoadjuvant therapy Its anti-tumor potential deserves further in-depth research, especially in the application of combination chemotherapy.

Future research should focus on:

• Pharmacokinetic and toxicological evaluation of the system.
• Validation of efficacy and safety in preclinical animal models.
• Formulation development and optimization of administration routes.
• In depth analysis of multi-target mechanisms of action.

Conclusion

As a natural flavonoid methoxy derivative with unique structure and multiple biological activities, luteolin tetramethyl ether exhibits excellent antioxidant, anti-inflammatory, and cell protective effects. It enhances cellular antioxidant defense by regulating key molecular targets such as NRF2, providing new ideas for the prevention and treatment of oxidative stress-related diseases. Although its low water solubility limits its pharmacokinetic performance, it is expected to overcome this bottleneck through modern pharmaceutical formulation technology and structural optimization. In the future, combined with systematic pharmacological research and preclinical evaluation, luteolin tetramethyl ether is expected to become an important candidate molecule for natural product drug development, promoting the application and development of natural flavonoids in modern medicine.