Product name: 4',5,7-Trimethoxyflavone
Synonym name: Apigenin-4',5,7-trimethyl ether
Catalogue No.: BP4183
Cas No.: 5631-70-9
Formula: C18H16O5
Mol Weight: 312.321
Botanical Source:
Physical Description:
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 4',5,7-Trimethoxyflavone
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
57.9000
3.0945
3.0945
.0024
3.4833
30.8369
High
89.3450
2.0162
Yes
No
Yes
No
Yes
No
0.6
No
Yes
No
Yes
Apigenin trimethyl ether (4',5,7-trimethoxyflavone, CAS No.: 5631-70-9) is a typical methoxyflavone compound. Due to its unique chemical structure and diverse bioactivity, it has attracted widespread attention in the field of natural product pharmacology in recent years. As a flavonoid ether naturally present in various plants, apigenin trimethyl ether not only exhibits good pharmacological activity but also possesses relatively ideal druggability parameters, making it a potential candidate for drug development.
Flavonoids are important components of plant secondary metabolites, widely distributed in vegetables, fruits, tea, and traditional Chinese medicinal materials, possessing antioxidant, anti-inflammatory, antitumor, and neuroprotective activities. Apigenin trimethyl ether, as a flavonoid derivative, significantly affects its physicochemical properties and biological activity through modification of methoxy groups, especially showing advantages in lipid solubility and cell membrane permeability. This paper aims to systematically review the chemical structure and physicochemical properties of apigenin trimethyl ether, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to explore its clinical application prospects, aiming to provide a theoretical foundation and research direction for subsequent development.
The chemical structure of apigenin trimethyl ether is based on a flavonoid backbone, specifically a flavonoid substituted with 4',5,7-trimethoxy. Its molecular formula is C18H16O5, and its molecular weight is 312.3210. In the structure, three methoxy groups (-OCH3) are located at positions 5 and 7 of the flavonoid A ring and 4' of the B ring, giving it unique physicochemical properties.
In terms of physicochemical properties, apigenin trimethyl ether exhibits high lipid solubility, with a LogP value of 3.0945, indicating good lipid solubility and cell membrane penetration ability. The polar surface area (TPSA) is 57.9 Ų, and moderate polarity helps its absorption and distribution within living organisms. Water solubility is relatively low, only 0.0024 mg/mL, indicating limited solubility in the aqueous phase and potentially affecting oral bioavailability. Notably, this compound has a high ability to penetrate the blood-brain barrier, indicating its potential advantage in treating central nervous system diseases.
In terms of safety, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity; The Ames mutagenic test value was 0.6, indicating a low genotoxicity risk and meeting drug safety requirements.
Apigenin trimether is mainly found in various medicinal and edible plants, especially in Apiaceae species such as celery (Apium graveolens), parsley (Petroselinum crispum), and some traditional Chinese medicinal materials rich in flavonoids. Although its content is not as high as the main active ingredient, as a secondary metabolite, it has important biological functions.
The extraction method typically uses organic solvent extraction combined with chromatography separation technology. Traditional extraction mostly uses methanol, ethanol, or ethyl acetate as solvents, followed by ultrasound-assisted extraction or reflux extraction to improve extraction efficiency. Purification and separation are then performed using silica gel column chromatography, high-performance liquid chromatography (HPLC), and other methods. In recent years, supercritical CO2 extraction and microwave-assisted extraction technologies have also been applied to the extraction of these flavonoids, significantly improving extraction efficiency and purity, and better aligning with green chemical principles.
During extraction, temperature, solvent polarity, and pH value significantly affect the stability and yield of apigenin trimethyl ether. To prevent demethylation of methoxy groups and degradation of the flavonoid backbone, extraction conditions must be strictly controlled, usually recommended for operation at low temperatures, protected from light, and in neutral to slightly acidic environments.
Apigenin trimethyl ether, as a multifunctional flavonoid compound, has demonstrated rich pharmacological activity in various in vitro and in vivo models, covering anti-inflammatory, anti-tumor, neuroprotective, antioxidant, and antimicrobial aspects.
Multiple studies have shown that apigenin trimethyl ether has inhibitory effects on various tumor cell lines, including breast cancer, lung cancer, colorectal cancer, and prostate cancer. Its mechanisms mainly involve inducing tumor cell apoptosis, inhibiting cell proliferation, and blocking the tumor cell cycle. In vitro experiments, this compound significantly reduced tumor cell survival rates and showed low toxicity to normal cells, demonstrating good selectivity.
Apigenin trimethyl ether can inhibit the release of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO), thereby reducing inflammatory responses. Its anti-inflammatory effects are evident in both acute and chronic inflammation models, suggesting its potential application value in inflammatory diseases such as arthritis and inflammatory bowel disease.
Due to its excellent blood-brain barrier penetration, apigenin trimethyl ether has attracted significant attention in research on neurological diseases. Research shows that this compound can alleviate oxidative stress, inhibit neuroinflammation, and promote nerve cell survival, providing protective effects against neurodegenerative diseases such as Parkinson's and Alzheimer's.
As a flavonoid compound, apigenin trimethyl ether has significant free radical scavenging capabilities, reducing oxidative damage and maintaining intracellular redox balance. Its antioxidant effects not only help prevent and treat chronic diseases but also provide the molecular basis for its anti-inflammatory and neuroprotective effects.
Preliminary studies have shown that apigenin trimethyl ether exhibits certain inhibitory effects on various bacteria and fungi, especially showing strong antibacterial activity against Gram-positive bacteria, suggesting its potential application in the field of anti-infection.
The multi-target mechanism of apigenin trimethyl ether forms the basis of its various pharmacological effects. By regulating multiple signaling pathways, this compound achieves comprehensive regulation of cellular function.
NF-κB pathway inhibition: Apigenin trimethyl ether can inhibit activation of the nuclear factor κB (NF-κB) signaling pathway, reduce the expression of inflammatory factors, and exert anti-inflammatory effects.
PI3K/Akt pathway regulation: This compound promotes cell apoptosis and inhibits tumor cell proliferation by modulating the PI3K/Akt signaling pathway.
MAPK pathway influence: Apigenin trimethyl ether regulates the activity of mitogen-activated protein kinase (MAPK) family members and participates in cellular stress responses and apoptosis processes.
Antioxidant-related pathways: By activating the Nrf2/ARE signaling pathway, cells enhance their antioxidant defenses and reduce oxidative damage.
Cell cycle regulatory proteins: such as Cyclin D1, CDK4/6, and apigenin trimethyl ether block the cell cycle by downregulating the expression of these proteins.
Apoptosis-related proteins: regulate the expression of Bcl-2 family proteins and promote apoptosis.
Inflammatory mediators: Inhibit the activity of enzymes such as iNOS and COX-2, reducing the formation of inflammatory mediators.
Neuroprotective targets: Regulates the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), promoting nerve repair.
Apigenin trimethyl ether showed relatively ideal characteristics in druggability evaluation. Its molecular weight of 312.3210 conforms to the Lipinski rule, with a LogP of 3.0945, indicating moderate lipid solubility and favorable cell membrane penetration. TPSA is 57.9 Ų, indicating moderate polarity and facilitating oral absorption. Lower water solubility (0.0024 mg/mL) may limit its oral bioavailability, but it can be improved through formulation optimization.
Its high permeability of the blood-brain barrier is its advantage in treating central nervous system diseases. hERG channels have no inhibitory effects, reducing the risk of cardiotoxicity. Ames test results indicate that it carries a low genotoxicity risk and is relatively safe.
Pharmacokinetics, although there is currently limited research on in vivo metabolism and kinetics of apigenin trimethyl ether, data indicate good oral absorption and widespread distribution in the body, especially high concentrations in brain tissue. The metabolic pathway mainly involves oxidation and methyl transfer reactions in the liver, with excretion primarily via bile and urine. Future studies are needed to systematically study its pharmacokinetic parameters, including half-life, bioavailability, and the activity and toxicity of metabolites.
Apigenin trimethyl ether, with its multi-target and multi-mechanism pharmacological activity, demonstrates broad clinical application potential. It holds significant development value especially in the fields of anti-tumor, anti-inflammation, and neuroprotection.
In the anti-tumor field, apigenin trimethyl ether can be used as an adjunct to chemotherapy, enhancing the efficacy of traditional drugs and reducing side effects. Its anti-inflammatory properties give it potential in treating chronic inflammatory diseases, especially autoimmune diseases and inflammation-related metabolic disorders.
Due to its excellent blood-brain barrier penetration, apigenin trimethyl ether offers unique advantages in treating neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In the future, combining nanocarrier technology with targeted drug delivery strategies is expected to enhance therapeutic efficacy and safety.
Additionally, the antioxidant and antimicrobial activities of apigenin trimethyl ether offer potential applications in preventing chronic and infectious diseases. With the continuous advancement of natural product drug development, structural optimization, formulation development, and preclinical evaluation of apigenin trimethyl ether will become key research priorities.
Future research should focus on:
Apigenin trimethyl ether, as a typical natural product of methoxyflavonoids, shows broad research and application prospects in the field of natural product pharmacology due to its unique chemical structure and diverse biological activities. Its excellent druggability parameters and safety have laid a solid foundation for its drug development. In the future, through multidisciplinary collaboration, in-depth exploration of its mechanism of action and clinical application potential is expected to promote the transformation of apigenin trimethyl ether into a novel drug, benefiting human health.
