Ingredients5,7-Dimethoxyflavone (abbreviated 5,7-DMF) is a naturally occurring polymethoxylated flavone belonging to the broader class of polyphenolic plant secondary metabolites. Its molecular formula is C17H14O4, and it is assigned PubChem CID 88881. Systematic synonyms include 5,7-Dimethoxy-2-phenyl-4H-1-benzopyran-4-one and chrysin dimethyl ether, with a CAS registry number of 21392-57-4 and a molecular weight of 282.29 g/mol. It is also commonly abbreviated as 5,7-DMF.
Chemically, 5,7-dimethoxyflavone is a dimethoxyflavone that is the 5,7-dimethyl ether derivative of chrysin. It belongs to the flavone subclass of flavonoids, distinguished by the presence of two methoxy (–OCH3) groups substituted at the C-5 and C-7 positions of the A-ring of the 2-phenylchromen-4-one (flavone) scaffold — positions that are hydroxylated in the parent compound chrysin. In its isolated form, it presents as a white crystalline powder soluble in organic solvents such as methanol, ethanol, and DMSO.
5,7-DMF is a pharmacologically active compound abundant in plant sources such as Kaempferia parviflora, Piper caninum, and Leptospermum scoparium, all of which have been used as folk medicine. Among these, the rhizome of K. parviflora is the primary commercial and scientific source.
Kaempferia parviflora Wall. ex Baker is a medicinal plant found in the upper northeastern regions of Thailand, belonging to the Zingiberaceae family. The most prominent botanical source of 5,7-DMF is the rhizome of Kaempferia parviflora, commonly known as black ginger or Thai ginseng. Polymethoxyflavones are identified as phytochemicals of the plant rhizomes with 5,7-dimethoxyflavone (DMF), 3,5,7-trimethoxyflavone (TMF), and 3,5,7,3′,4′-pentamethoxyflavone (PMF) as the main constituents.
Kaempferia parviflora (Krachaidum) is a Thai herb whose rhizomes have been used in folk medicine and ritual ceremonies, and its increasing commercial use has raised concerns regarding variation in the quality, potency, and efficacy of products derived from it. Analysis of the bioactive compounds in black ginger has identified more than 140 individual ingredients.
5,7-DMF occurs in the plant material predominantly as part of a complex mixture of polymethoxyflavones and is not typically isolated as a single ingredient in commercial preparations; rather, it is a key analytical marker of standardized extracts.
Black ginger, the rhizome of Kaempferia parviflora (Zingiberaceae), has traditionally been used as a food and folk medicine for more than 1,000 years in Thailand. In Thai traditional medicine, the rhizome, known locally as Krachaidum or black ginger, has been utilized for centuries to treat a variety of ailments through decoctions prepared by boiling the rhizome. These preparations are commonly employed to alleviate allergies, asthma, gout, diarrhea, peptic ulcers, and colic, reflecting its role as a versatile remedy in folk healing practices.
K. parviflora, originally found in the north and northeast of Thailand, is popular as a health-promoting herb and has traditionally been used as folk medicine for managing a variety of diseases, including inflammation, ulcers, gout, colic disorder, abscesses, allergy, and osteoarthritis. The rhizomes of Kaempferia parviflora have been used in Thai traditional medicine for health promotion and for the treatment of digestive disorders and gastric ulcer.
Beyond medicinal use, the rhizomes of Kaempferia parviflora (Krachaidum) have been used in folk medicine and ritual ceremonies. Wine preparations made from the fresh rhizome are increasingly used in Thailand as a tonic and as an aphrodisiac.
Ethnopharmacologically, the plant rhizomes have long been used as community medicines among hill tribe people to promote health and increase life-longevity. In folk medicine, K. parviflora rhizomes are used to improve blood flow and treat inflammatory, allergic, and gastrointestinal disorders.
Reputed for its aphrodisiac effect, rhizomes of Kaempferia parviflora have been used as traditional medicine for various medicinal purposes including a tonic for rectifying male erectile dysfunction. In traditional medicine, rhizomes are brought to boil or soaked with alcohol, and used to drink as an elixir to improve sexual performance.
Kaempferia parviflora, Piper caninum, and Leptospermum scoparium — all sources of 5,7-DMF — have been used as folk medicine to treat gastrointestinal disorders, infections, and hypertension. Extracts from K. parviflora have traditionally been used to treat asthma, rheumatoid arthritis, skin diseases, and wounds for decades.
5,7-DMF is one member of a broader family of polymethoxyflavones (PMFs) found in K. parviflora. Black ginger extract is rich in polymethoxy flavonoids (PMF), which exhibit various bioactivities. The major co-occurring methoxyflavones include 3,5,7-trimethoxyflavone (TMF), 5,7,4′-trimethoxyflavone, and 3,5,7,3′,4′-pentamethoxyflavone (PMF). 5,7-Dimethoxyflavone is a major compound from Kaempferia parviflora.
Structure–activity relationship analysis shows that the methoxyl group at the C-5 position of 7-methoxyflavones is necessary for PDE5 inhibition. The presence and positioning of the two methoxy groups at C-5 and C-7 on the flavone A-ring distinguish 5,7-DMF from its unmethylated parent chrysin and confer distinct biological properties, including improved lipophilicity and metabolic stability relative to hydroxylated flavones.
5,7-Dimethoxyflavone has been identified as a potential lead compound for the development of selectively potent PDE5 inhibitors for clinically efficacious treatment of erectile dysfunction. This investigation arose from the question of whether traditional aphrodisiac plants might contain substantial amounts of PDE5 inhibitors. Forty-one plant extracts and eight 7-methoxyflavones from Kaempferia parviflora were screened for PDE5 and PDE6 inhibitory activities using a two-step radioactive assay. This finding provides an explanation for enhancing sexual performance in the traditional use of Kaempferia parviflora; moreover, 5,7-dimethoxyflavones were identified as useful lead compounds to further develop clinically efficacious PDE5 inhibitors. The PDE5 inhibition observed for 5,7-DMF is characterized as low-affinity relative to approved pharmaceutical agents.
The anti-inflammatory activity of 5,7-DMF has been formally assessed; it was found to possess a comparable effect to aspirin on the rat paw edema model, though it showed no inhibition of cotton pellet-induced granuloma formation. On the rat pleurisy model, 5,7-DMF exhibited an antiexudative effect, interfered with leukocyte migration, and markedly inhibited prostaglandin biosynthesis. In addition, 5,7-DMF caused marked lowering of the rectal temperature of rats. This prostaglandin synthesis inhibition, antiexudation, and leukocyte migration suppression together represent the documented mechanistic basis for the compound's anti-inflammatory profile.
The antiobesity effect of 5,7-DMF was evaluated in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese C57BL/6J mice. 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 PPARγ, C/EBPα, and SREBP-1c, as well as lipid synthesis enzymes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), and HMG-CoA reductase (HMGR).
Polymethoxy flavonoids in K. parviflora extract including 5,7-dimethoxyflavone enhanced the expression of GLUT4 and PGC-1α, and 5,7-dimethoxyflavone enhanced the phosphorylation of 5′AMP-activated protein kinase (AMPK). AMPK is a master regulator of energy homeostasis; its activation by 5,7-DMF is proposed to underlie the compound's effects on glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.
DMF stimulated the PI3K–Akt pathway, consequently activating the mTOR–4EBP1–p70S6K pathway for protein synthesis. DMF reduced the mRNA expression of E3 ubiquitin ligase- and autophagy-lysosomal-related genes involved in proteolysis via the phosphorylation of FoxO3. DMF upregulated PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM), along with the increase of relative mitochondrial DNA content.
K. parviflora extract was studied for its effect on endothelial function. Studies in human umbilical vein endothelial cells (HUVEC) showed that it dose-dependently increased nitrite concentrations in culture media after 48 h incubation, and eNOS mRNA and protein expression were also enhanced. The induction of eNOS mRNA was detected at 4 h and reached a plateau at 48 h, while iNOS expression was not observed.
5,7-Dimethoxyflavone inhibits cytochrome P450 (CYP) 3As and is also a potent Breast Cancer Resistance Protein (BCRP) inhibitor. Compared to control animals, 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.
5,7-DMF is a natural flavonoid that was reported to be a potent BCRP inhibitor. The effect of 5,7-DMF on the disposition of sorafenib, a tyrosine kinase inhibitor that is a good substrate of BCRP, was investigated both in vitro in efflux transporter-expressing cells and in vivo in mice. 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-Dimethoxyflavone (DMF) and 5,7,4′-trimethoxyflavone (TMF) are natural methoxyflavones known for their potential neuroprotective properties. Target proteins for DMF predicted through in silico modeling include GABRA1, GABRG2, 5-HT2A, IGF1R, and 5-HT2C. Both DMF and TMF significantly reduced Aβ, IL-1β, IL-6, and TNF-α levels, while DMF-treated groups significantly increased BDNF levels in LPS-induced memory-impaired mice.
Evidence level: Preclinical (in vivo animal models and in vitro). No controlled human trials specifically on 5,7-DMF as an isolated compound.
The anti-inflammatory activity of 5,7-DMF has been assessed; it was found to possess a comparable effect to aspirin on the rat paw edema model (though with no inhibition of cotton pellet-induced granuloma formation), and on the rat pleurisy model, it exhibited an antiexudative effect, interfered with leukocyte migration, and markedly inhibited prostaglandin biosynthesis. These results — published in a 1989 study in Planta Medica — represent foundational preclinical evidence. All anti-inflammatory data for the isolated compound are from animal or cell-based models; no randomized controlled trials (RCTs) have been conducted specifically with isolated 5,7-DMF in human subjects.
Evidence level: Preclinical (cell lines and rodent models) and limited human clinical evidence from K. parviflora extract studies.
In cell and animal research, the antiobesity effect of 5,7-DMF was evaluated in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese C57BL/6J mice, demonstrating dose-dependent suppression of lipid droplet and triglyceride accumulation through inhibition of adipogenesis.
At the clinical level, evidence derives from trials using whole K. parviflora extract (KPE), not isolated 5,7-DMF. One study examined the safety and efficacy of K. parviflora extract (SIRTMAX®) on obesity, glucose and lipid metabolism, and arterial stiffness in humans using a randomized, double-blind, placebo-controlled crossover design. Twenty-seven healthy volunteers received either a test product containing 100 mg of SIRTMAX® or placebo by oral administration for 7 weeks. Body weight and fasting blood glucose declined significantly (P=0.0033 and P=0.04, respectively) in the SIRTMAX® group. Another RCT — a randomized, double-blind, placebo-controlled clinical study — found that daily intake of K. parviflora extract decreased abdominal fat in overweight and pre-obese Japanese subjects, as indexed in the Cochrane Central Register.
These clinical results are promising but methodologically limited: sample sizes were small, and the active constituent responsible for the effects cannot be attributed solely to 5,7-DMF because KPE contains multiple PMFs.
Evidence level: In vitro and animal studies for 5,7-DMF specifically; human evidence is for KPE, not the isolated compound.
DMF stimulated the PI3K-Akt pathway, activating the mTOR–4EBP1–p70S6K protein synthesis cascade, reduced mRNA expression of proteolysis-related genes via FoxO3 phosphorylation, upregulated PGC-1α, NRF1, and TFAM along with increased mitochondrial DNA content, alleviated inflammatory responses by reducing TNF-α and IL-6, and — collectively — was proposed as a natural agent to inhibit sarcopenia via improving protein turnover and mitochondrial function.
An in vitro test using C2C12 myoblasts showed that several PMFs including 5,7-dimethoxyflavone improved muscular metabolism and suppressed muscular inflammatory responses. Physical fitness performance and muscular endurance were superior in mice orally administered KPE (45 mg/kg/day) for 4 weeks compared to control mice. Moreover, KPE enhanced physical fitness — including grip strength, leg muscle strength, balance, endurance, and locomotor activity — in athletes, the elderly, and healthy individuals in human trials.
Evidence level: Mechanistic in vitro data and limited pilot clinical data for KPE; isolated 5,7-DMF identified as a low-affinity PDE5 inhibitor in preclinical assays.
5,7-Dimethoxyflavone has been identified as a potential lead compound for PDE5 inhibitor development, and the investigation arose from the intent to determine whether traditional aphrodisiac plants might contain substantial amounts of PDE5 inhibitors. PDE5 is the enzymatic target of pharmaceutical agents such as sildenafil used for erectile dysfunction. The affinity of 5,7-DMF for PDE5 was described as low relative to pharmaceutical-grade inhibitors.
From current clinical trials using KPE, results found that Krachaidum significantly enhanced sexual erotic stimuli, but these findings were based on only one study. A 2018 pilot study mentioned in the literature administered K. parviflora ethanol extract for 30 days to 14 elderly adult men with erectile dysfunction, and the majority reported statistically significant improvements in erectile function on self-assessed questionnaires. This pilot study is preliminary, unblinded, and insufficient to establish efficacy.
It is necessary to conduct high-quality clinical trials to verify the dosage, targeted patients, and therapeutic effects, and further pharmacology experiments are also needed to identify the active compounds.
Evidence level: In silico and animal model studies. No human clinical data available for 5,7-DMF in this indication.
A recent study investigated neuroprotective mechanisms of DMF through in silico target predictions and memory-impaired mice. Ligand-based and proteochemometric models were used to predict potential protein targets, followed by molecular docking. DMF and TMF (10/20/40 mg/kg) were administered to LPS-induced mice for 21 days, and Morris Water Maze and Open Field Test were conducted to assess cognitive functions. TMF enhanced spatial memory in the Morris Water Maze, while both compounds reduced anxiety-related measures. DMF significantly upregulated hippocampal mRNA of GABRA1, 5-HT2A, and 5-HT2C. Additionally, both compounds significantly reduced Aβ, IL-1β, IL-6, and TNF-α levels, while DMF-treated groups significantly increased BDNF levels. These findings suggest that DMF and TMF exert neuroprotective effects acting through distinct molecular targets involved in neurotransmission and inflammation. Their multi-target activity makes them described as promising candidates for early intervention in Alzheimer's disease, based on these preclinical findings.
Evidence level: In vitro cell lines and in vivo animal models. No human clinical trials.
5,7-DMF has demonstrated many beneficial pharmacological effects in vitro, including anti-inflammatory, anti-oxidant, cardioprotection effects, as well as chemopreventive and chemosensitizing properties. The chemosensitizing activity is primarily mechanistically linked to its inhibition of BCRP. Bcrp1-mediated DMF–drug interactions occur both in vitro and in vivo. 5,7-DMF represents a novel and very promising chemosensitizing agent for BCRP-mediated multidrug resistance due to its low toxicity and potent BCRP inhibition.
Structural modifications of 5,7-DMF have been explored. Two oxime derivatives synthesized from 5,7-DMF exhibited cytotoxicity against HepG2 cell line with IC50 values of 36.38 and 25.34 μg/mL, respectively, and against T47D cell line with IC50 values of 41.66 and 22.94 μg/mL; one compound showed cytotoxicity against HepG2 and T47D cell lines with IC50 values of 21.36 and 25.00 μg/mL. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. These results are from in vitro experiments on derivative compounds, not 5,7-DMF itself, and have no established clinical applicability.
Evidence level: In vitro only.
An oxime derivative of 5,7-DMF exhibited antifungal activity against Candida albicans with an IC50 value of 48.98 μg/mL in preclinical cell-based testing. Antifungal data apply to synthetic derivatives rather than the parent 5,7-DMF molecule.
Evidence level: Animal model studies. No dedicated human trials for 5,7-DMF.
5,7-Dimethoxyflavone is a major bioactive in Kaempferia parviflora, which has been used as food and folk medicine to treat digestive disorders, gastric ulcer, and oral diseases. Preclinical research has demonstrated anti-gastric ulcer effects of K. parviflora in animal models.
In contrast to extensive in vitro investigations, pharmacokinetic (PK) profile data for 5,7-DMF in vivo are limited. In one study, the PK and tissue distribution of 5,7-DMF in mice following a single oral dose of 10 mg/kg were investigated. Mouse plasma, heart, lung, liver, kidney, intestine, brain, spleen, muscle, and fat tissues were collected and analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Maximal 5,7-DMF concentrations in plasma and tissues were reached within 30 minutes.
Among peripheral organs, the AUCs of 5,7-dimethoxyflavone were found in descending order as follows: liver > kidney > spleen > heart > lung. This distribution pattern indicates preferential accumulation in metabolically active organs. These data derive from mouse studies and may not directly reflect human pharmacokinetics.
The following dosages have been specifically reported in published research. These are descriptive and derive exclusively from cited studies; no established therapeutic dose for humans exists for isolated 5,7-DMF.
Note that all human trial doses are for whole plant extracts standardized to include 5,7-DMF among other PMFs, not for isolated 5,7-DMF. The contribution of pure 5,7-DMF at these extract doses has not been determined in controlled human studies.
Of 683 records identified in one systematic review, only 7 studies were included. From current clinical trials, Krachaidum showed positive benefits but remained inconclusive since only small studies were included. The major bioactive compounds — the methoxyflavones — have been investigated for their anti-obesity, anti-diabetes, physical performance, and aphrodisiac properties; however, clinical studies are limited.
The scientific literature as a whole reflects a substantial body of in vitro and animal research with promising mechanistic findings, but human clinical trial evidence is sparse, small in sample size, and almost exclusively pertains to whole extracts of K. parviflora rather than isolated 5,7-DMF. Attribution of specific clinical effects to 5,7-DMF alone — versus to the full PMF mixture — has not been established in any human trial to date.
In a randomized double-blind placebo-controlled safety study, there were no adverse events related to KPE intake or any abnormalities compared with placebo group in anthropometric, cardiovascular, blood, and urine parameters during the course of the study; daily KPE ingestion was found to be safe in healthy Japanese men and women.
In the 2016 systematic review of clinical studies, no adverse events were reported even when Krachaidum was used at 1.35 g/day.
A well-documented and pharmacologically significant concern is the inhibition of cytochrome P450 3A (CYP3A) enzymes. Kaempferia parviflora extract has attracted attention as a dietary supplement in Japan, but there is little information regarding food–drug interactions (FDIs). The key FDI concern is inhibition of CYP3A, a typical drug-metabolizing enzyme. The inhibitory effects of KP extract and its main ingredients, 5,7-DMF and 3,5,7,3′,4′-PMF, on CYP3A-mediated midazolam 1′-hydroxylation activity were investigated in human liver microsomes.
KP extract competitively inhibited MDZ 1′-OH activity with an inhibition constant value of 78.14 µg/mL, which was lower than the estimated concentration in the small intestine after ingestion. Furthermore, KP extract, 5,7-DMF, and 3,5,7,3′,4′-PMF inhibited the activity in a time-, NADPH-, and concentration-dependent manner.
In one in vivo mouse study, the area under the curve (AUC) of midazolam (a CYP3A substrate) increased by 130% and its biological half-life was extended by approximately 100 minutes in the group administered 5,7-DMF. 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.
Mechanism-based inhibition (MBI) is an important drug interaction mechanism in which a reactive metabolic intermediate produced by CYP irreversibly inactivates this enzyme, potentially leading to long-lasting severe adverse effects. Even foods can cause this severe inhibition — as is the case with grapefruit juice — and it is therefore important to investigate whether KP extract causes MBI of CYP3A, since this enzyme is involved in the metabolism of many clinically important drugs.
5,7-DMF is implicated in the inhibition of the Breast Cancer Resistance Protein (BCRP), also known as ABCG2. BCRP is an ATP-binding cassette (ABC) transporter that plays a significant role in multidrug resistance in cancer by actively pumping chemotherapeutic drugs out of cancer cells. This inhibitory effect of 5,7-DMF on efflux transporters like P-gp and BCRP suggests its potential use as a chemosensitizing agent to overcome multidrug resistance in cancer therapy and to improve the oral bioavailability of certain drugs. Conversely, this effect creates a risk of altered plasma levels of drugs that are BCRP substrates (including certain tyrosine kinase inhibitors and antibiotics) when co-administered with 5,7-DMF or KPE.
Hippocratic screening revealed that 5,7-DMF possesses a weak CNS depressant activity. This finding, from preclinical pharmacological screening, has not been investigated in human studies; its clinical significance is unknown.
Health conditions that 5,7-dimethoxyflavone may help support.
Body systems that 5,7-dimethoxyflavone may help support.
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