Ingredients7-Methoxyflavone (systematic IUPAC name: 7-methoxy-2-phenyl-4H-1-benzopyran-4-one, also rendered as 7-methoxy-2-phenylchromen-4-one or 2-phenyl-7-methoxy-4H-1-benzopyran-4-one) is a naturally occurring, oxygen-methylated member of the flavone subclass of polyphenolic flavonoids.
Its molecular formula is C₁₆H₁₂O₃ and it is listed in PubChem under Compound ID (CID) 466268. It carries the Chemical Abstracts Service (CAS) Registry Number 22395-22-8, the molecular formula C₁₆H₁₂O₃, and a formula weight of approximately 252.3 daltons. According to ChEBI classification, 7-methoxyflavone is a member of the flavonoids and an ether.
Structurally, the compound is built on the classical 2-phenylchromen-4-one (flavone) backbone — a benzopyranone fused bicyclic ring system bearing an unsubstituted phenyl (B-ring) at the 2-position — with a single methoxy (–OCH₃) substituent at the 7-position of the A-ring. This distinguishes it from close structural analogs such as chrysin (5,7-dihydroxyflavone) and 7-hydroxyflavone, from which it can be regarded as a methyl-ether derivative. In its pure form it is a crystalline solid, soluble in DMF (30 mg/ml), DMSO (15 mg/ml), and ethanol (5 mg/ml). Reference-grade commercial material appears as a white to light-yellow powder or crystal, with a reported melting point range of 109–113°C and purity of ≥98.0% by gas chromatography.
Among its synonyms in the chemical literature are: 7-methoxy-2-phenyl-chromone; 7-methoxoyflavone; METHOXYFLAVONE, 7-; and 4H-1-Benzopyran-4-one, 7-methoxy-2-phenyl-.
7-Methoxyflavone is a flavonoid compound that can be isolated from Zornia brasiliensis. This member of the Fabaceae (legume) family is the principal documented natural source from which the pure compound has been isolated for research purposes.
Zornia brasiliensis Vogel (Leguminosae) is a species popularly known in Brazil as "urinária", "urinana", and "carrapicho". According to the Royal Botanic Gardens Kew (Plants of the World Online), the native range of this species is the Venezuelan Antilles to Brazil, and it is a subshrub growing primarily in the seasonally dry tropical biome. Z. brasiliensis is distributed in the North, Northeast, Center-West, and Southeast regions of Brazil, and is associated with the Amazon, Caatinga, Cerrado, and Atlantic Forest phytogeographic domains.
The compound is not exclusive to Z. brasiliensis. 7-Methoxyflavone is found in various plant species, including Zornia brasiliensis, Conchocarpus heterophyllus, and Pimelea simplex. Some methoxylated flavones, the broader group to which 7-methoxyflavone belongs, are particularly abundant in citrus fruits. Though methylated flavonoids are widely present in plants, their levels are usually low.
The historical use of 7-methoxyflavone as an isolated compound is essentially absent from the ethnobotanical record, as isolated single-molecule preparations are a product of modern organic chemistry. However, the plants from which it has been isolated carry documented traditional histories.
Zornia brasiliensis Vogel (Fabaceae), popularly known as "urinária," "urinana," and "carrapicho," is used in Brazilian northeast folk medicine to treat venereal diseases and as a diuretic. The whole plant is used as a diuretic and to treat disorders of the urinary system, and is also used in the treatment of venereal diseases; a traditional preparation involves a handful of the plant decocted in a litre of water, drunk instead of water until symptoms disappear. The plant is harvested from the wild for local use as a medicine.
Several secondary metabolites have been isolated from Zornia brasiliensis (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal effects.
It is important to note that Z. brasiliensis preparations used in traditional medicine are whole-plant or whole-extract preparations; the attribution of any traditional therapeutic effect specifically to 7-methoxyflavone is an inference made by contemporary researchers and is not documented in traditional ethnobotanical records as such.
7-Methoxyflavone is itself the active compound under investigation, not a crude extract. It belongs to the methoxylated flavone (also termed polymethoxyflavone) subgroup within the broader flavonoid polyphenol class. Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation.
Chemically, the distinction of 7-methoxyflavone from its unmethylated parent (7-hydroxyflavone) is pharmacologically significant. Methylation of free phenolic hydroxyl groups produces derivatives not susceptible to glucuronic acid or sulfate conjugation, resulting in increased metabolic stability. Methylation also leads to greatly improved transport through biological membranes, such as in intestinal absorption, and much increased oral bioavailability.
The most thoroughly documented mechanism of 7-methoxyflavone is competitive inhibition of aromatase (cytochrome P450 19A1, CYP19A1), the enzyme responsible for converting androgens (including testosterone and androstenedione) to estrogens. 7-Methoxyflavone is a natural, non-steroidal compound because it binds reversibly with aromatase, an enzyme that helps produce estrogen through the conversion of androgen (testosterone) to estrogen.
The foundational work on flavone-mediated aromatase inhibition was published in 1984 by Kellis and Vickery in the journal Science. Several naturally occurring and synthetic flavones were found to inhibit the aromatization of androstenedione and testosterone to estrogens catalyzed by human placental and ovarian microsomes. These flavones include (in order of decreasing potency) 7,8-benzoflavone, chrysin, apigenin, flavone, flavanone, and quercetin; 5,6-benzoflavone was not inhibitory. 7,8-Benzoflavone and chrysin were potent competitive inhibitors and induced spectral changes in the aromatase cytochrome P-450 indicative of substrate displacement. Flavones may thus compete with steroids in their interaction with certain monooxygenases and thereby alter steroid hormone metabolism.
A key 2007 study by Ta and Walle, published in the Journal of Steroid Biochemistry and Molecular Biology, specifically investigated methylated flavones including 7-methoxyflavone as aromatase inhibitors. Previous studies had shown chrysin, 7-hydroxyflavone and 7,4′-dihydroxyflavone to be the most potent flavonoid inhibitors of aromatase. However, very poor oral bioavailability is a major limitation for the successful use of dietary flavonoids as chemopreventive agents. The researchers showed that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone, and 7,4′-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have much higher intestinal absorption. In this study, they examined these fully methylated flavones as potential aromatase inhibitors for the prevention and/or treatment of hormone-dependent cancers.
Whereas 5,7-dimethoxyflavone had poor effect compared to its unmethylated analog chrysin, 7-methoxyflavone and 7,4′-dimethoxyflavone were almost equipotent to their unmethylated analogs, with IC₅₀ values of 2 to 9 μM. A separate source reports the aromatase inhibition IC₅₀ for 7-methoxyflavone as 1.9 µM in a cell-free assay.
7-Methoxyflavone activates androgen and/or glucocorticoid receptor transcriptional activity in a reporter assay. This was demonstrated in a study using an in vitro reporter gene system. The effect of 32 flavonoids on androgen (AR) and glucocorticoid receptors (GR) was investigated using an MDA-kb2 human breast cancer cell line to predict potential AR and GR activities. Among the compounds tested, 5-hydroxyflavone had the highest AR antagonistic activity with an IC₅₀ value of 0.3 µM, whereas 6-methoxyflavone had the highest induced luciferase activity with an EC₁₅₀ value of 0.7 µM. These findings provide evidence of a fundamental property of the structure-activity relationship of flavonoids with AR and/or GR. This receptor modulation study is significant but confined to an in vitro cell line model; results in this assay involving 7-methoxyflavone (as opposed to 6-methoxyflavone) are referenced as supporting data in several commercial research databases.
Natural flavonoids with bioactivity as secondary plant metabolites are mostly found in fruits, vegetables, tea, and herbs; their distribution and bioavailability in vivo depends on the interaction and successive binding with carrier proteins in the systemic circulation. The binding behavior of 7-methoxyflavone (7-MF) with human serum albumin (HSA) has been studied with the aid of multi-spectroscopic methods, molecular docking, and molecular dynamic simulation. The results of multi-spectroscopic experiments revealed that 7-MF interacted with HSA predominantly via fluorescence static quenching and the microenvironment around the fluorophore Trp residues in HSA became more hydrophilic with the binding of 7-MF. Thermodynamic analysis demonstrated that hydrogen bonds and van der Waals forces played a dominant role in stabilizing the HSA-7-MF complex. This study (He et al.) provides physicochemical evidence for how 7-methoxyflavone is likely transported in human blood.
7-Methoxyflavone inhibits LPS-induced nitric oxide (NO) production by 17.74% in RAW 264.7 macrophages when used at a concentration of 20 µM. This inhibitory effect on lipopolysaccharide-stimulated macrophage NO production is preliminary (in vitro, single cell line) and the magnitude of effect is modest at the tested concentration.
7-Methoxyflavone is effective against chemical pain but has no significant effect on thermal pain. The proposed mechanism is peripheral in nature, engaging pathways triggered by chemical algogenic stimuli (including glutamatergic nociception) rather than central opioid or thermal pathways. See Section 6.2 for detail on the preclinical study supporting this.
In experiments using human liver S9 fraction, 7-methoxyflavone was relatively stable compared to its unmethylated analogs, indicating high resistance to hepatic metabolism. The low bioavailability of unmethylated flavones is mainly due to highly efficient glucuronic acid and sulfate conjugation in the intestinal/hepatic barrier. Methyl capping of all free hydroxyl groups results in dramatically increased metabolic stability, as the metabolism is shifted to less efficient CYP-mediated oxidation.
In Caco-2 intestinal cell experiments, methylated flavones showed approximately 5- to 8-fold higher apparent permeability (Papp 22.6–27.6 × 10⁻⁶ cm s⁻¹) of apical to basolateral flux than unmethylated flavones (Papp 3.0–7.8 × 10⁻⁶ cm s⁻¹). Similarly, 7-methoxyflavone, 7,4′-dimethoxyflavone, and 5,7,4′-trimethoxyflavone were much more metabolically stable and had higher transport rates than the corresponding unmethylated flavones.
Evidence type: In vitro (biochemical cell-free assays, cell line reporter assays). No human clinical trials identified in the scientific literature.
The aromatase-inhibitory potential of 7-methoxyflavone has been documented in enzyme-based biochemical assays. Studies have shown that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone, and 7,4′-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have much higher intestinal absorption. These fully methylated flavones were examined as potential aromatase inhibitors for the prevention and/or treatment of hormone-dependent cancers. Whereas 5,7-dimethoxyflavone had poor effect compared to its unmethylated analog chrysin, 7-methoxyflavone and 7,4′-dimethoxyflavone were almost equipotent to their unmethylated analogs, with IC₅₀ values of 2–9 µM.
The significance of this finding rests partly on the bioavailability advantage of methoxylated flavones over hydroxylated ones. The oral bioavailability of chrysin was lacking circumstantial clinical evidence. By contrast, methoxylated analogs like 7-methoxyflavone display greater metabolic stability, potentially making them better candidates for in vivo aromatase inhibition — though this has not yet been confirmed in human trials.
Evidence strength: Preliminary. All evidence is in vitro (cell-free enzyme or cell line). No randomized controlled trials or clinical pharmacokinetic/pharmacodynamic studies in humans have been identified in the peer-reviewed literature. The clinical relevance of in vitro IC₅₀ values for aromatase inhibition is uncertain without corresponding human data.
Evidence type: Animal studies (mice, in vivo). No human clinical trials identified.
The most detailed preclinical investigation of 7-methoxyflavone's analgesic potential was published in Natural Product Research in 2013 by da Silva et al. In this study, the antinociceptive effect of 7-methoxyflavone (7MF) in mice was investigated using the following tests: acetic acid-induced writhing, glutamate- and formalin-induced nociception, and hotplate.
It has been reported that 7-methoxyflavone (7MF) isolated from Zornia brasiliensis reduces abdominal constriction behavior, inhibits the neurogenic phase of the formalin pain response, and decreases glutamate-induced nociception without affecting the thermal response latency in the hotplate test. The inability of 7MF to modify hotplate latency may be ascribed to the use of lower doses (≤300 µmol/kg, i.p.).
Evidence strength: Preliminary preclinical only. All studies are in rodent models, with intraperitoneal administration. No human clinical evidence exists. The peripheral selectivity of the antinociceptive effect (effective against chemical, not thermal, pain) is a mechanistically interesting finding but requires human translation studies.
Evidence type: In vitro (cell lines) and in vivo (rodent models) for the broader class of methoxylated flavones; indirect for 7-methoxyflavone specifically. No human clinical trials identified.
Dietary flavones have promising chemoprotective properties, in particular with regard to cancer, but problems with low oral bioavailability and sometimes unacceptable toxicity have made their use as protective additives to normal diets questionable. However, methylation of free phenolic hydroxyl groups leads to derivatives not susceptible to glucuronic acid or sulfate conjugation, resulting in increased metabolic stability. Methylation also leads to greatly improved transport through biological membranes, and much increased oral bioavailability. Recent studies also indicate that methylation results in derivatives with increasing potency to kill cancer cells. They also show high potency towards inhibition of hormone-regulating enzymes such as aromatase, which is important in the causation of breast cancer.
Studies on closely related methoxylated flavones have demonstrated anti-proliferative activity: In human oral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone were both ten times more potent inhibitors of cell proliferation (IC₅₀ values 5–8 µM) than the corresponding unmethylated analogs chrysin and apigenin. Flow cytometry indicated that both methylated flavones arrested the SCC-9 cells in the G1 phase with a concomitant decrease in the S phase, dramatically different from the unmethylated analogs, which promoted G2/M phase arrest. While these findings involve dimethoxylated rather than monomethoxylated analogs, they are relevant to the mechanistic class.
Epidemiological context has been noted in the literature: A very recent (at time of publication) epidemiological study provided support for methoxylated flavones as potential cancer chemopreventive dietary agents. This prospective study in 42,311 men in the Health Professionals Follow-up Study convincingly showed that histologically diagnosed oral premalignant lesions were suppressed by consumption of citrus fruits and citrus fruit juices (a 30–40% lower risk), whereas, surprisingly, vegetables provided no protection — this was described as the first epidemiological study providing evidence of protective effects of a subclass of dietary fruits and vegetables. However, this study pertains to methoxylated flavones from citrus broadly, not 7-methoxyflavone specifically, and is observational in nature.
Evidence strength: For 7-methoxyflavone specifically, evidence is in vitro and in vitro/cell-free only. The class-level evidence for methoxylated flavones in chemoprevention is more developed but remains largely preclinical. No clinical trials of 7-methoxyflavone in any cancer indication have been identified.
Evidence type: In vitro only (macrophage cell lines).
As noted above, 7-methoxyflavone inhibits LPS-induced nitric oxide (NO) production by 17.74% in RAW 264.7 macrophages at a concentration of 20 µM. This constitutes a modest inhibitory effect at a relatively high concentration in an in vitro inflammation model. No in vivo animal or human anti-inflammatory studies using 7-methoxyflavone specifically as the test compound have been identified in peer-reviewed literature.
Evidence strength: Weak and preliminary. A single in vitro finding at one concentration in a macrophage cell line model; the clinical significance is entirely unknown.
Evidence type: No clinical or human data identified. The proposed rationale is mechanistic (via aromatase inhibition).
Some athletes and bodybuilders are interested in 7-methoxyflavone for increasing testosterone levels, building muscle, and improving athletic performance. 7-Methoxyflavone might change how the body breaks down chemicals called hormones. Some people think this might cause the body to have more of the hormone called testosterone. However, more evidence is needed to rate 7-methoxyflavone for these uses. The theoretical pathway — aromatase inhibition → reduced testosterone-to-estrogen conversion → elevated circulating testosterone — is plausible in principle but has not been tested in any human trial.
Evidence strength: No human evidence. The claim is mechanistically extrapolated from in vitro aromatase inhibition data.
The pharmacokinetic profile of 7-methoxyflavone is one of its more extensively studied attributes, explored specifically in the context of the bioavailability advantage of methoxylated versus hydroxylated flavones.
The low bioavailability of unmethylated flavones is mainly due to highly efficient glucuronic acid and sulfate conjugation of these mono- or polyhydroxylated agents in the intestinal/hepatic barrier. Methyl capping of all free hydroxyl groups results in dramatically increased metabolic stability, as the metabolism is shifted to less efficient CYP-mediated oxidation. This was demonstrated using the human liver S9 fraction with an appropriate selection of cofactors. In addition, intestinal transport of flavones was much improved through methylation, as shown in Caco-2 cell Transwell experiments.
In vivo in the rat, oral administration of one methylated flavone resulted in high bioavailability and tissue distribution, with no detectable levels of its unmethylated analogue. In addition to increased metabolic stability, methylation resulted in markedly increased inhibition of cancer cell proliferation.
The binding behavior of 7-MF with human serum albumin (HSA) has been characterized via multi-spectroscopic methods, molecular docking, and molecular dynamic simulation. 7-MF interacted with HSA predominantly via fluorescence static quenching; thermodynamic analysis demonstrated that hydrogen bonds and van der Waals forces played a dominant role in stabilizing the HSA–7-MF complex. This binding interaction is pharmacologically relevant because HSA serves as the primary transport protein for many small molecule phytochemicals in circulation.
No human pharmacokinetic data (e.g., bioavailability fraction, elimination half-life, volume of distribution, or Cmax in human volunteers) for 7-methoxyflavone have been identified in the peer-reviewed literature.
The appropriate dose of 7-methoxyflavone depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for 7-methoxyflavone.
The only peer-reviewed dose data for 7-methoxyflavone pertain exclusively to animal experiments. The following doses are reported specifically in these studies:
Commercial dietary supplement formulations containing 7-methoxyflavone exist, typically as oral powder or capsule forms. However, no clinical dose-ranging studies have been published, and any doses listed on supplement products have not been validated in controlled human studies.
There is not enough reliable information to determine whether 7-methoxyflavone is safe or to characterize its side effects. Formal human safety studies have not been published in the peer-reviewed literature.
Available preclinical safety data come from the source plant's extract rather than the isolated compound. For the ethanolic extract of Z. brasiliensis aerial parts, the concentration that produced 50% hemolysis (HC₅₀) was 1,954 µg/ml, indicating low cytotoxicity. In acute toxicity assay in mice, no deaths or behavioral changes were recorded at 2,000 mg/kg of the extract. Regarding repeated-dose evaluation, after 28 days of treatment with the extract (250, 500, and 1,000 mg/kg, oral gavage), weak toxicity signs on biochemical, hematological, and neurological parameters were observed, especially for the highest dose tested. These data pertain to the whole plant extract, not 7-methoxyflavone as a pure compound.
Aromatase inhibitor medications: 7-Methoxyflavone might have effects that are similar to some medications used for estrogen-sensitive cancers (aromatase inhibitors); caution is warranted with this combination. Concurrent use with pharmaceutical aromatase inhibitors (such as anastrozole, letrozole, or exemestane) could potentially produce additive or unpredictable effects on estrogen levels.
Prostate conditions: 7-Methoxyflavone might cause the body to have more of the hormone testosterone. This hormone might worsen symptoms of an enlarged prostate (benign prostatic hyperplasia).
Cytochrome P450 interactions: Because 7-methoxyflavone is itself a modulator of CYP19A1 (aromatase) and falls within a chemical class that interacts with multiple CYP enzymes, potential interactions with CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4-metabolized drugs are theoretically possible, though no direct interaction data for this specific compound in human systems have been published.
There is not enough reliable information about the safety of taking 7-methoxyflavone if pregnant or breast-feeding. Avoidance of use is recommended on the precautionary principle.
7-Methoxyflavone occupies an ambiguous regulatory position. It is sold as a dietary supplement ingredient in some markets, often in formulations targeting hormone balance or athletic performance. 7-Methoxyflavone is a chemical found in certain plants. It can also be produced in a laboratory. Synthetic production allows for purity levels typically used in research settings.
Methylation of flavones may also result in derivatives with diminished toxic side-effects and improved aqueous solubility — an advantage cited in the research context. However, the compound has not received monograph status from major pharmacopoeial bodies (USP, European Pharmacopoeia, WHO, or ESCOP), and no regulatory body (FDA, EFSA, EMA) has issued a formal opinion on its use as a dietary supplement ingredient. No entry for 7-methoxyflavone was identified in the NIH Office of Dietary Supplements fact sheets or NCCIH resources at the time of writing.
The table below summarizes the quality and strength of evidence for 7-methoxyflavone's investigated activities:
Overall, 7-methoxyflavone is a pharmacologically active natural compound with a scientifically interesting profile — particularly its dual advantage of aromatase inhibitory potency and superior metabolic stability relative to unmethylated analogs — but the totality of its evidence base remains confined to in vitro and preclinical animal models. As of the available literature, no human clinical trials have been conducted or completed evaluating efficacy, safety, or pharmacokinetics of 7-methoxyflavone as an isolated compound.
Health conditions that 7-methoxyflavone may help support.
Body systems that 7-methoxyflavone may help support.
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