IngredientsDimethyl chrysin is most precisely known in the scientific literature as 5,7-dimethoxyflavone (abbreviated 5,7-DMF or DMF). It is also called chrysin dimethyl ether or chrysin 5,7-di-O-methyl ether, reflecting its direct structural derivation from the parent flavone chrysin (5,7-dihydroxyflavone). The compound's formal chemical name is 5,7-dimethoxyflavone (chrysin 5,7-di-O-methyl ether). Its CAS registry number is 21392-57-4.
The parent molecule, chrysin, is a yellow powder with the chemical name 5,7-dihydroxy-2-phenyl-4H-chromen-4-one, with molecular formula C15H10O4 and molecular weight 254.24. It is a dihydroxyflavone in which the two hydroxy groups are located at positions 5 and 7. In 5,7-dimethoxyflavone, both of these hydroxyl groups have been methylated — that is, each phenolic —OH has been replaced by a methoxy group (—OCH3) — yielding a structurally more lipophilic analogue. Under conditions employing excess electrophile (typically more than two equivalents), both hydroxyl groups can be alkylated, allowing for further structural diversification. The resulting compound is a light tan powder with melting point 147–149 °C.
Flavonoids are phenolic compounds that form a subclass of phenylpropanoids characterized by a common skeleton composed of three rings (C6-C3-C6); these rings can be enzymatically modified to generate chalcones, flavanones, flavones, isoflavones, flavonols, anthocyanidins, and flavanols. Dimethyl chrysin belongs to the flavone subclass. The specific bioactivity and potency of flavonoids depend on the decoration of the basic scaffold, mainly with hydroxyl, methoxyl, glycosyl, and acyl groups. The dimethylation of chrysin's hydroxyls represents one such modification, with documented consequences for metabolic stability and bioavailability compared to the parent compound.
5,7-Dimethoxyflavone occurs naturally in the plant kingdom, most prominently in the rhizomes of Kaempferia parviflora Wall. ex Baker. Kaempferia parviflora is a medicinal plant found in the upper northeastern regions of Thailand, which belongs to the Zingiberaceae family. It is also known as black ginger or "krachai dum" in Thai. 5,7-Dimethoxyflavone is a major compound from Kaempferia parviflora. K. parviflora contains several flavonoids, including 5,7-dimethoxyflavone, 5-hydroxy-3,7,4′-trimethoxyflavone, and 5-hydroxy-3,7-dimethoxyflavone.
The compound also appears, in smaller amounts, as a constituent in the broader flavonoid chemical space of the genus Passiflora and other plants that produce chrysin and its methylated derivatives. The parent flavone chrysin itself is found in honey, propolis, the passion flowers Passiflora caerulea and Passiflora incarnata, and in Oroxylum indicum. The amount of chrysin in honey from various plant sources is about 0.2 mg per 100 g; a 2010 study found the amount of chrysin was 0.10 mg/kg in honeydew honey, and 5.3 mg/kg in forest honeys. A 2010 study found the amount of chrysin in propolis was as much as 28 g/L. 5,7-DMF is the O-methylated counterpart of this parent scaffold. Because the dimethylated form requires methyltransferase-mediated biosynthetic steps not present in all plant taxa, it is concentrated primarily in K. parviflora.
In research settings, 5,7-dimethoxyflavone is used as an isolated, purified compound. The present study aims to investigate the standardization parameters, to analyze chemical constituents of volatile oil by gas chromatography-mass spectrometry, and to determine the content of 5,7-dimethoxyflavone in K. parviflora rhizomes by thin-layer chromatography (TLC)-densitometry. As a dietary supplement, DMF is typically delivered as an ethanolic or standardized extract of K. parviflora rhizome, often in capsule or powder form. The percent yield of ethanolic extracts of K. parviflora rhizomes was 9.57 ± 1.49 g/100 g by dry weight. Synthetic preparation of the compound is also possible via standard methylation of chrysin with dimethyl sulfate and a base. 5,7-Dimethoxyflavone is prepared similarly to monomethylated chrysin derivatives, but with excess dimethyl sulphate.
Like its parent molecule chrysin, 5,7-dimethoxyflavone's clinical translation is hampered by poor aqueous solubility, low bioavailability, and rapid metabolic clearance; to address these limitations, extensive synthetic efforts have focused on generating structurally diverse chrysin derivatives that possess improved drug-like properties. Advanced delivery systems such as solid lipid nanoparticles and polymer-based nanoformulations are under investigation for chrysin-class flavones more broadly.
The traditional use of dimethyl chrysin as an isolated compound is not documented in historical herbalism; the historical record concerns K. parviflora rhizome as a whole plant material, with 5,7-DMF subsequently identified as its principal bioactive constituent. Black ginger, scientifically known as Kaempferia parviflora, has a long history of use in traditional medicine, particularly in Southeast Asia. Black ginger is a food crop and herbal plant native to Southeast Asia; it has been used for centuries in traditional Asian medicine for its numerous health benefits, particularly antioxidant and anti-inflammatory activities.
In Thailand, where the plant is native and most intensively cultivated, traditional preparations employed the dried or fresh rhizome (underground stem). In herbal medicine, it is generally used to promote health and to cure gastrointestinal disorder and anti-inflammation; it is also used as an aphrodisiac for stimulating sexual performance in males; it has traditionally been used to improve vitality and treat metabolic ailments; K. parviflora could be eaten either fresh or as dry rhizome before physical performance to improve physical work capacity. Rhizomes of black ginger have traditionally been used to relieve symptoms of gastrointestinal disorder and inflammation. It has been traditionally used as a health-promoting alternative medicine with anti-inflammatory, anti-allergic, anticholinesterase, adaptogenic, and anti-obesity effects.
The rhizome was most commonly prepared as a decoction (boiled in water), blended into rice whisky-based tonics, or consumed directly as sliced dried root. Traditionally, K. parviflora was used for gastrointestinal disorders, allergies, as sexual stimulants, and body nourishment. The plant's traditional role as an energizing tonic and aphrodisiac in Thai folk medicine has subsequently attracted scientific investigation into the mechanisms of its major methoxyflavone constituents, foremost among them 5,7-DMF.
Dimethyl chrysin (5,7-DMF) is the fully O-methylated analogue of chrysin. 5,7-Dimethoxyflavone (DMF) is a methylated analog of chrysin. This distinction is pharmacologically important: chrysin's two free hydroxyl groups at positions 5 and 7 render it susceptible to phase II conjugation (glucuronidation and sulfation) in the gut and liver, dramatically limiting its oral bioavailability. Methylation blocks these conjugation sites.
Recent findings indicate that methylated flavones have the advantage of increased metabolic stability; one such compound, the naturally-occurring 5,7-dimethoxyflavone (5,7-DMF), has been shown to be a potential chemopreventive agent in human cancer originating from the liver, mouth, esophagus and lung. Studies directly comparing the two analogues in biological models confirm the advantage: 5,7-DMF accumulated 20-fold to 100-fold in all tissues examined, with the highest accumulation in liver and brain, whereas chrysin was barely detectable in any tissues except the liver. The bile of chrysin-exposed fish contained very low concentrations of unchanged chrysin but high concentrations of two glucuronic acid conjugates. In the bile of 5,7-DMF-exposed fish, the parent compound was detectable in significant amounts along with glucuronic acid conjugates of O-demethylated 5,7-DMF. The investigators concluded that 5,7-DMF demonstrated high tissue accumulation and limited metabolism compared to chrysin in vivo, making this flavone a promising chemopreventive molecule.
Upon metabolism in vivo, DMF undergoes partial O-demethylation back to chrysin or mono-methoxyflavone intermediates. Two metabolites of DMF — chrysin and 5-methoxy-7-hydroxyflavone — were found after incubating DMF with human intestinal bacteria or orally administering K. parviflora. This means some of DMF's pharmacological activity in vivo may be mediated by these demethylated metabolites.
The rhizome of K. parviflora is most popularly used and investigated, with polymethoxyflavones as the main bioactive phytoconstituent. Additional methoxyflavones isolated from the rhizome include 5,7,4′-trimethoxyflavone and 3,5,7,3′,4′-pentamethoxyflavone. 5,7-Dimethoxyflavone and 5,7,4′-trimethoxyflavone are key constituents of K. parviflora extract and are highly absorbable into the body. For the purposes of this article, the focus is on the 5,7-dimethoxyflavone component.
5,7-DMF, like its parent chrysin, exerts anti-inflammatory effects through suppression of key transcriptional and enzymatic regulators of inflammation. Chrysin demonstrates anti-inflammatory action through several mechanisms: it suppresses cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis that promotes inflammation; it inhibits phosphorylation and degradation of IκB-α, as well as the translocation of NF-κB. Studies have shown that chrysin inhibits monocyte secretion of IL-1β, IL-2, IL-6, IL-12, and TNF-α, promotes IL-4 secretion, and reduces metabolically active succinate dehydrogenase activity in LPS-stimulated PBMCs, while down-regulating the expression of iNOS, COX-2, and NF-kB. The dimethylated form recapitulates these pathways with improved tissue penetration.
The biological activity of flavonoids has been attributed mainly to their intrinsic antioxidant capacity; this allows them to scavenge free radicals and thus reduce or prevent damage to cells. For chrysin-class flavones, the antioxidant mechanism involves enhancement of endogenous antioxidant enzymes. Chrysin modulates critical signalling pathways, such as PI3K/Akt/mTOR and JNK, while enhancing antioxidant defences through increased activity of enzymes like superoxide dismutase and glutathione peroxidase.
A mechanistic feature of particular interest for 5,7-DMF is its inhibition of phosphodiesterase type 5 (PDE5), the enzyme that degrades cyclic GMP (cGMP) and is the target of pharmaceutical agents used for erectile dysfunction. The most potent PDE5 inhibitor in K. parviflora was 5,7-dimethoxyflavone, with an IC50 of 10.64 ± 2.09 μM and a selectivity for PDE5 over PDE6 of 3.71. Structure activity relationship showed that the methoxyl group at the C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition; K. parviflora rhizome extract and its 7-methoxyflavone constituents had moderate inhibitory activity against PDE5; this finding provides an explanation for enhancing sexual performance in the traditional use of Kaempferia parviflora.
5,7-Dimethoxyflavone (5,7-DMF) is an inhibitor of cytochrome P450 (CYP) 3As that markedly decreases the expression of CYP3A11 and CYP3A25 in the liver. This compound is also a potent Breast Cancer Resistance Protein (BCRP, ABCG2) inhibitor. These enzyme-interaction properties have important implications for drug metabolism and are discussed in the safety section below.
5,7-Dimethoxyflavone is a natural flavonoid that is a potent BCRP inhibitor. In a study examining the effect of 5,7-DMF on the disposition of sorafenib — a tyrosine kinase inhibitor and BCRP substrate — 5,7-DMF significantly inhibited Bcrp1-mediated sorafenib efflux in a concentration-dependent manner in MDCK/Bcrp1 cells, with an EC50 value of 8.78 μM. 5,7-DMF can also increase the accumulation of doxorubicin in A549 cells as a result of suppression of multidrug resistance proteins (MRPs).
In many studies chrysin-class compounds have been shown to exert beneficial pharmacological activities: they suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), upregulated apoptotic pathways, inhibited angiogenesis and metastasis formation, suppressed DNA topoisomerases and histone deacetylase, downregulated tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β). The anti-tumour mechanism may include inhibition of PI3K/AKT signalling pathway and mitochondrial dysfunction.
The accumulation of lipid droplets and triglycerides in adipocytes was dose-dependently suppressed by DMF through inhibition of adipogenesis. DMF downregulated the adipogenic transcription factors (peroxisome proliferator-activated receptor [PPAR]γ, CCAAT/enhancer binding protein [C/EBP]α, and sterol regulatory element-binding protein-1c [SREBP-1c]) and lipid synthesis enzymes (fatty acid synthase [FAS], acetyl-CoA carboxylase [ACC], lipoprotein lipase [LPL], and HMG-CoA reductase [HMGR]). AMP-activated protein kinase (AMPK) and AMPK-related lipolytic proteins in differentiated adipocytes were activated by DMF.
In the context of skeletal muscle, DMF stimulated the phosphatidylinositol 3-kinase-Akt pathway, consequently activating the mammalian target of rapamycin–eukaryotic initiation factor 4E-binding protein 1–70-kDa ribosomal protein S6 kinase pathway for protein synthesis; DMF also reduced the mRNA expression of E3 ubiquitin ligase- and autophagy-lysosomal-related genes involved in proteolysis via phosphorylation of Forkhead box O3.
The anticancer evidence for 5,7-dimethoxyflavone consists almost entirely of in vitro cell line studies and preclinical animal experiments. No clinical trials in humans have been identified in the peer-reviewed literature for this specific compound.
In vitro evidence: The efficacy of 5,7-dimethoxyflavone (DMF) as a therapeutic agent to treat acute lymphoblastic leukaemia (ALL) was investigated using a panel of ALL cell lines; the IC50 varied between 2.8 and 7.0 μg/mL; DMF induced G0/G1 cell cycle arrest, concomitant with a decreased expression of phosphorylated retinoblastoma-associated protein 1; DMF increased the rate of apoptosis, although it was apparent only after a long period of exposure (96 h). However, the accumulation of oxidative stress was not involved in the growth-inhibitory effects of DMF in that model, and notably, DMF also antagonized the cytotoxicity of co-administered conventional anticancer drugs, limiting its therapeutic utility in combination regimens.
Chrysin dimethyl ether (5,7-DMF) is a natural compound that has been found to inhibit skin cancer in mice, and it has been shown to inhibit the growth of human carcinoma cell lines and other cancer cells. The mechanism of action for this compound is not yet fully known, but it has been shown to affect energy metabolism, mitochondrial membrane potential, and enzyme activities in vitro.
5,7-Dimethoxyflavone has been shown to be a potential chemopreventive agent in human cancer originating from the liver, mouth, esophagus, and lung in cell-based studies. 5,7-DMF can prevent hepatic carcinogenesis by inhibiting cytochrome P450 (CYP) 1A1 activity, which subsequently decreased the carcinogen benzo[a]pyrene (BaP)-induced DNA adduct formation, a mechanistically relevant chemopreventive observation.
A 2014 study published in Cancer Prevention Research examined a chrysin derivative (compound 69407, structurally related to chrysin dimethyl ether) in a two-stage skin carcinogenesis model in mice. Compound 69407 was identified as a novel MSK1 inhibitor; it was more potent and less toxic than chrysin in suppressing proliferation and TPA-induced neoplastic transformation of JB6 P+ cells; moreover, using a two-stage skin carcinogenesis protocol with DMBA as initiator and TPA as the promoter, compound 69407 exerted a significant anti-promotion effect; further studies revealed that it appeared to exert its inhibitory effects on TPA-induced skin tumour promotion through direct inhibition of MSK1/histone H3 signalling.
Evidence strength: Overall, the oncology evidence for 5,7-DMF is preliminary and preclinical. No randomized clinical trials or phase I/II studies in human cancer patients have been published for this specific compound as of the available literature.
5,7-Dimethoxyflavone was reported to induce apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway (Phytotherapy Research, 2020). This in vitro study is the primary evidence base for this indication; no clinical studies have been identified. Evidence strength is very preliminary (single in vitro study).
A 2020 peer-reviewed study published in Nutrients (Kim & Hwang, Yonsei University) used an aged mouse model to investigate DMF's effects on sarcopenia. Eighteen-month-old mice were orally administered DMF at the dose of 25 mg·kg−1·day−1 or 50 mg·kg−1·day−1 for 8 weeks; DMF not only stimulated grip strength and exercise endurance but also increased muscle mass and volume. Mechanistically, DMF upregulated peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A along with the increase of relative mitochondrial DNA content; DMF also alleviated inflammatory responses by reducing the tumour necrosis factor-alpha and interleukin-6 serum and mRNA levels. The investigators concluded that DMF can be used as a natural agent to inhibit sarcopenia via improving protein turnover and mitochondria function.
Bei et al. provided scientific evidence that DMF was distributed to several tissues, such as the intestine, the liver, the brain, and fats, as well as the muscle through blood circulation after a single oral administration of DMF; since the aging process seizes not just the muscle but also all other tissues, DMF may not only directly improve the cell signalling in the sarcopenic muscle but also affect the aging process of other tissues.
Evidence strength: This is an animal-only study. No human clinical trials for DMF's effects on sarcopenia have been published in the available peer-reviewed literature.
A study published in Journal of Medicinal Food (2016) evaluated DMF's anti-obesity properties in cell culture and a high-fat diet (HFD) mouse model. In the animal model, oral administration of DMF at 50 mg/kg/day for 6 weeks significantly decreased body weight gain without affecting food intake. At the molecular level, this was attributed to suppression of the transcription factors PPARγ, C/EBPα, and SREBP-1c, along with AMPK activation. 5,7-Dimethoxyflavone also decreased HFD-induced body weight gain, reducing the protein expression of transcription factors involved in lipogenesis such as PPARγ, C/EBP/α, and SREBP-1c in adipose tissue.
Evidence strength: Evidence is preclinical (in vitro and rodent models only). No human clinical trials have been identified for this indication.
The traditional use of K. parviflora as an aphrodisiac has been investigated biochemically. The most potent PDE5 inhibitor identified in a screening of K. parviflora constituents was 5,7-dimethoxyflavone (IC50 = 10.64 ± 2.09 μM, selectivity on PDE5 over PDE6 = 3.71). This finding provides an explanation for enhancing sexual performance in the traditional use of Kaempferia parviflora; moreover, 5,7-dimethoxyflavones are considered useful lead compounds to further develop clinically efficacious PDE5 inhibitors.
Evidence strength: The PDE5 inhibitory mechanism is established in vitro, but PDE5 inhibitory potency at 10.64 μM is considerably weaker than approved pharmaceutical PDE5 inhibitors (e.g., sildenafil, IC50 ~3.5 nM). Evidence for clinical efficacy in sexual dysfunction is absent from the peer-reviewed literature at this time.
K. parviflora extract results from a study using a monoiodoacetic acid rat osteoarthritis (OA) model revealed that the extract reduced pain threshold and severity of osteoarthritic cartilage lesions; the mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes; the extract, as well as 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage.
Evidence strength: Preclinical animal model and in vitro chondrocyte data only. No human trials identified.
Chrysin (the parent of DMF) has been extensively studied for neuropsychiatric effects. Chrysin exerts a neuropharmacological effect in brain structures such as the amygdala, hippocampus, prefrontal cortex, and raphe nucleus; the effects include the activation of the GABAergic system by modulating the GABAA/benzodiazepine receptor complex, changes in serotonin levels and modification in the expression of their receptors such as 5-HT1A and 5-HT2A in the raphe nucleus and hippocampus, and restoration of dopamine and noradrenaline levels in the CNS. Tissue distribution studies confirm that 5,7-DMF accumulated 20-fold to 100-fold in all tissues examined, with the highest accumulation in liver and brain, suggesting DMF reaches CNS targets more effectively than chrysin. However, direct clinical human data on DMF's neurological effects remain absent from the literature.
No human clinical dosing data are available for dimethyl chrysin (5,7-DMF). The following dosages appear in published preclinical studies only and cannot be extrapolated to humans:
The most thoroughly characterized safety concern for 5,7-DMF is its inhibition of the cytochrome P450 3A (CYP3A) enzyme family, which is responsible for metabolizing a large proportion of pharmaceutical drugs. 5,7-DMF markedly decreased the expression of CYP3A11 and CYP3A25 in the liver; these results suggest that continued ingestion of 5,7-DMF decreases the expression of CYP3As in the liver, consequently increasing the blood concentrations of drugs metabolized by CYP3As. In the experimental model, the AUC of midazolam (a CYP3A substrate) increased by 130% and its biological half-life was extended by approximately 100 minutes in 5,7-DMF-treated mice compared to controls. This finding implies a clinically significant potential for pharmacokinetic drug–drug interactions in any human co-administering 5,7-DMF with CYP3A-metabolized drugs such as immunosuppressants, statins, benzodiazepines, or certain antiretrovirals.
5,7-DMF can increase the accumulation of doxorubicin in A549 cells as a result of suppression of MRPs; 5,7-DMF demonstrated very potent BCRP inhibition both in vitro and in vivo even at low micromolar concentrations. The plasma and tissue concentrations of mitoxantrone, an anticancer drug with high affinity to BCRP, were significantly increased in vivo with the co-administration of 5,7-DMF. This broad inhibitory effect on P-gp, BCRP, and MRPs represents a second clinically relevant interaction pathway: co-administration with anticancer drugs that are substrates of these efflux pumps could lead to elevated drug concentrations and toxicity, though in oncological contexts this could also be exploited to overcome multidrug resistance.
In the acute lymphoblastic leukaemia in vitro study, while DMF reduced cell proliferation, DMF increased the rate of apoptosis only after a long period of exposure (96 h) and was found to antagonize the cytotoxic activity of co-administered standard chemotherapy agents in ALL cell lines. This represents a potential concern for patients undergoing cancer treatment who might consider self-supplementing with K. parviflora extracts.
Chrysin, a naturally occurring flavonoid, exhibits a broad spectrum of biological activities, including anticancer properties; however, its clinical application is limited by poor bioavailability and low solubility. The methylated form, 5,7-DMF, addresses the bioavailability limitations but simultaneously gains the CYP3A and BCRP inhibitory properties to a greater degree than chrysin, given its higher tissue accumulation. Methylated flavones have the advantage of increased metabolic stability, but this same property means the compound persists longer in tissues and systemic circulation, potentially amplifying enzyme-inhibitory interactions with co-medications.
No systematic clinical safety trials, Phase I pharmacokinetic studies in humans, or regulatory-level toxicological assessments have been identified in the peer-reviewed literature for isolated 5,7-dimethoxyflavone as a dietary supplement. The evidence base consists exclusively of preclinical (in vitro and animal) studies. Despite promising therapeutic potential, limitations such as low bioavailability and the lack of comprehensive clinical studies warrant further investigation.
Dimethyl chrysin (5,7-dimethoxyflavone) is a well-characterized natural compound with a defined chemical identity (CAS 21392-57-4), a principal botanical source (Kaempferia parviflora rhizome), a coherent mechanistic profile spanning anti-inflammatory, antioxidant, PDE5-inhibitory, CYP3A-inhibitory, and BCRP-inhibitory activities, and a growing body of preclinical evidence across oncology, metabolic disease, sarcopenia, and sexual health. Its pharmacokinetic advantage over chrysin — markedly improved tissue accumulation and metabolic stability — makes it scientifically interesting as a bioavailability-enhanced polyphenol.
However, across all proposed health applications, the evidence is confined to in vitro cell studies and animal models. The use of 5,7-DMF for metabolic syndrome is primarily supported by preclinical scientific studies, rather than historical or traditional medicine; animal studies and in vitro experiments have reported that DMF may exert beneficial effects on several features of metabolic syndrome. K. parviflora demonstrated antioxidant, anti-inflammatory, anti-obesity, anticancer, vascular relaxation, and antimicrobial effects; in humans, there is evidence of its general benefits on physical fitness — though this relates to whole-plant extract studies rather than isolated DMF. No published randomized controlled trials, dose-finding studies, or formal safety assessments in humans have been identified for 5,7-dimethoxyflavone as an isolated compound as of the current literature review.
Health conditions that Dimethyl chrysin may help support.
Body systems that Dimethyl chrysin may help support.
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