IngredientsFlavones are a discrete subclass within the broader superfamily of flavonoids — low molecular weight polyphenolic phytochemicals secreted as secondary metabolites in plants. The basic structure of flavonoids has a skeleton of diphenyl propane containing 15 carbon atoms: two 6-membered rings (A and B) linked with 3 carbon units that may or may not be part of a third ring, the heterocyclic oxygen-containing pyrone ring — a configuration referred to as the C6-C3-C6 structure.
What distinguishes flavones specifically within this family is a precise set of structural features. Flavones differ from other flavonoids in that they have a double bond between C2 and C3 in the flavonoid skeleton, there is no substitution at the C3 position, and they are oxidized at the C4 position. Among flavonoids, flavones do not have oxygen-containing groups at the "3" position; if there is a hydroxyl or other oxygen-containing group at the "3" position, they are known as flavonols. This structural distinction is chemically important, because the presence or absence of this C3 hydroxyl group dramatically influences reactivity, antioxidant capacity, and biological activity.
Luteolin and apigenin are the most abundant flavones occurring in nature. Other characterized flavones include baicalein, scutellarein, lucenin-2, vicenin-2, diosmetin, nobiletin, tangeretin, and 5-O-methyl-scutellarein. Additionally, chrysin and wogonin are well-studied members of this structural class.
In chemical nomenclature these compounds carry systematic IUPAC names reflecting their hydroxylation and methoxylation patterns. As illustrative examples: luteolin is 3′,4′,5,7-tetrahydroxyflavone and apigenin is 4′,5,7-trihydroxyflavone. Apigenin bears three phenolic hydroxyl groups, while luteolin carries four OH-groups including an ortho-dihydroxy structure in the B ring — a feature essential for effective free radical scavenging.
In natural sources, flavonoids may occur in free forms (aglycones), as glycosylated or acylated derivatives, and as oligomeric and polymeric structures. Almost all natural flavonoids exist in plants in O-glycosides or C-glycosides forms; C-glycosides are sugar moieties combined directly to the flavonoid backbone as C–C covalent bonds. Several thousand flavonoids have been identified in plant sources, and the number of compounds increases when considering the flavonoid-derived products that can be formed during the processing and storage of foodstuffs, and the metabolites and conjugates produced in the human organism after their intake.
In their ecological role within plants, flavones serve multiple functions. They play a variety of roles in plants: along with flavonols, they are the primary pigments in white- and cream-colored flowers and act as copigments with anthocyanins in blue flowers. Flavones and other flavonoids can also act as UVB protectants in plants, because they absorb in the 280- to 315-nm range. Their synthesis can be upregulated by UV light in parsley cells, resulting in apigenin and luteolin concentrations in celery leaves more than 20 times higher than those in stalks; field-grown plants have higher concentrations than greenhouse-grown plants. Flavones can also act as natural pesticides in plants, providing protection against insects and fungal diseases.
Flavonoids are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. More specifically for the flavone subclass, luteolin and apigenin are the main flavones found in food, such as onions, celery, red pepper, and grapes. Luteolin is found in cereals and herbs, and glycosylated luteolin in vegetables such as carrots and broccoli.
Chamomile and parsley have the highest flavone concentrations, with as much as 5,320 mg apigenin O-glycosides/100 g dried chamomile flowers or 1,350 mg/100 g dried parsley leaf. Fresh parsley had the highest flavone concentrations of the fresh foods, with up to 1,484 mg apigenin/100 g.
The apigenin conjugates in chamomile have been identified as acetyl, malonyl, and caffeoyl derivatives of apigenin 7-O-glucoside, whereas those in parsley are predominantly apigenin 7-O-malonyl apiosylglucoside (malonylapiin) and apigenin 7-O-apiosylglucoside (apiin).
Teas are another significant dietary source. Luteolin 8-C-glucoside (orientin) and luteolin 6-C-glucoside (isoorientin) are most abundant in rooibos tea. Green, black, and oolong teas contain orientin and isoorientin, as well as a variety of apigenin mono- and di-C-glycosides.
Citrus fruits, juices, and related products stand out as classical sources of flavones, owing to the fact that they are grown almost everywhere and are commonly part of the diet of people from the vast majority of countries and cultures. The polymethoxylated flavones nobiletin and tangeretin are found predominantly in citrus peel.
Scutellaria baicalensis Georgi, known as "Huangqin" in its dried root form, is a herb widely used in traditional Chinese medicine. Baicalin, baicalein, wogonin, and wogonoside are the main flavonoid compounds found in it. These include baicalin (5,6,7-trihydroxyflavone 7-O-β-D-glucuronide), baicalein (5,6,7-trihydroxyflavone), wogonoside (5,7-dihydroxy-8-methoxyflavone 7-O-β-D-glucuronide), and wogonin (5,7-dihydroxy-8-methoxyflavone).
Humans consume, on average, between 0.45 and 1.17 mg of apigenin daily. Overall flavonoid intake from the diet is modest: an estimated less than 80 mg of flavonoids are taken each day across all subclasses by the average person, though this varies greatly with diet and geographic region.
Chamomile is one of the most ancient medicinal herbs known to mankind. The dried flowers of chamomile contain many terpenoids and flavonoids contributing to its medicinal properties. Chamomile preparations have been commonly used for many human ailments such as hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Many different preparations of chamomile have been developed, the most popular of which is in the form of herbal tea consumed more than one million cups per day. At present, 26 countries around the world have included this plant in their pharmacopoeia.
A total of fifty flavonoids have been isolated from chamomile and are its main active components; they include quercetin, apigenin, luteolin, and rutin. These compounds exhibit antibacterial, antioxidant, anticancer, and other pharmacological effects. The flavone apigenin is particularly concentrated in chamomile flowers, where it occurs primarily as glycoside derivatives including apigenin 7-O-glucoside.
Scutellaria baicalensis is a member of the Labiataceae family and its dried roots have long been used in traditional Chinese medicine. It is known as "Huangqin" in its dried root form and has been used for "clearing away heat, removing dampness, purging fire and detoxification." Wogonin extracted from the root of Scutellaria baicalensis has long been used as a traditional medicine in East Asian countries.
In traditional Chinese medicine, flavonoid-containing herbs have been used for a variety of medicinal purposes, including treatment or prevention of cardiovascular disease, cancer, and inflammation. This ancient practice reflects a deep-rooted understanding of using flavonoid-rich botanicals alongside other natural compounds to create synergistic healing effects.
Parsley (Petroselinum crispum) — among the densest dietary sources of apigenin — has been used in European herbal traditions for diuretic, digestive, and anti-inflammatory purposes for centuries. Researchers worldwide have been interested in discovering the potential of flavonoids and other polyphenols, used in traditional medicines and taken from medicinal plants, in relation to medical and pharmaceutical applications.
Oroxylum indicum (L.) Benth. ex Kurz, known as Pheka, is a plant in the Bignoniaceae family with various traditional uses. The mature fruits promote anti-helminthic and stomachic effects, while the seeds have been used as a purgative and for the relief of tonsil pain. The young fruits are popularly consumed as vegetables, while the seeds are one of the components in traditional drink formulations. The pods, seeds, and root bark of this plant contain many flavonoids such as baicalein, biochanin A, oroxylin A, chrysin, apigenin, and their glycosides.
It is important to note that traditional uses were for the whole plant or crude extract, not for isolated flavones specifically. The attribution of historical therapeutic effects to individual flavone constituents is a retroactive scientific interpretation, as the concept of isolating and identifying individual flavone molecules emerged only in the 20th century. Many studies on the health benefits of flavonoids and other polyphenols have been tested using in silico, in vitro, and in vivo models; however, few studies have been carried out using clinical trials that have trustworthy subject sizes and are in accordance with clinical practice guidelines.
Apigenin (4′,5,7-trihydroxyflavone) is one of the most studied dietary flavones. Apigenin is a natural plant flavone abundantly common in chamomile, parsley, onions, grapefruit, oranges, and plant-derived beverages, with antioxidative and antiproliferative effects reported in human cancers of the breast, cervix, colon, lung, ovary, prostate, skin, thyroid, and liver in preclinical studies.
Luteolin (3′,4′,5,7-tetrahydroxyflavone) is the structurally closely related counterpart to apigenin, differing by the presence of one additional hydroxyl group. Luteolin is widely found in fruits, vegetables, flowers, and herbs, and exhibits a variety of beneficial pharmacological properties with significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, and anti-cardiovascular aspects.
Baicalein, a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi and fruits of Oroxylum indicum, has been shown to exhibit strong free radical scavenging. Baicalin is the glucuronide glycoside of baicalein and the predominant form found in the plant. Among Scutellaria compounds, flavonoids such as baicalein, baicalin, wogonin, wogonoside, and oroxylin-A attract the most attention because of their high concentration and excellent effects.
Wogonin (5,7-dihydroxy-8-methoxyflavone) is isolated from Scutellaria baicalensis Georgi and has positive activities on insulin sensitivity, blood glucose, and lipid metabolism through selective AMPK and PPARα signals.
Chrysin (5,7-dihydroxyflavone) is found in propolis, passionflower, and honey. It is one of the simplest naturally occurring flavones and has been investigated for antioxidant and anti-inflammatory properties, though its oral bioavailability is notably poor.
Nobiletin and tangeretin are polymethoxylated flavones found in citrus peel that differ from the more common hydroxylated flavones in that their phenolic hydroxyl groups are replaced by methoxy groups, altering their pharmacokinetics and activities. Wogonin and tangeretin increase claudin-1 and zonula occludens-1 in tight junctions; they also reduce IL-6, IL-1β, IL-8, iNOS, and COX-2; and TLR4, MyD88, TAK1, IL-23, and TNF-α expression. Tangeretin also decreases T-helper cells in Th1 and Th17 differentiation.
Many luteolin-containing plants possess antioxidant properties associated with the capacity to scavenge reactive oxygen and nitrogen species (ROS, RNS), to inhibit pro-oxidant enzymes, and to induce antioxidant enzymes, as observed in vitro and in vivo. Apigenin, with three phenolic hydroxyl groups, has a lower Trolox equivalent antioxidant capacity (TEAC) than luteolin, which bears four OH-groups including an ortho-dihydroxy structure in the B ring — a configuration essential for effective free radical scavenging by dissociation of hydroxyl functions.
At the cellular level, flavones activate endogenous antioxidant defense. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect; they inhibit the secretion of enzymes such as lysozymes and β-glucuronidase, and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions.
Luteolin was identified as the most potent flavonoid in inhibiting TNF-alpha release from macrophages, in blocking lipopolysaccharide (LPS)-induced activation of the nuclear factor-kappa B (NF-κB) and IL-6 production by inhibition of the JNK and AP1-signaling pathways.
The potential mechanism of action of luteolin has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/β-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2 signaling pathways.
Apigenin was the most potent inhibitor of transcriptional activation of both inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide-activated RAW 264.7 cells among flavonoids including wogonin, luteolin, tectorigenin, kaempferol, and quercetin, reducing the production of nitric oxide.
Apigenin and luteolin decrease inflammatory bowel disease by regulating TNF-α, IL-1β, iNOS, and COX-2 expression, and luteolin was also observed to reduce CD4+ T cell infiltration.
Flavonoids modulate several cell-signaling pathways, including PI3K/Akt, JAK/STAT, MAPK, and NF-κB, to exert anticancer and anti-inflammatory effects. They reduce inflammation and oxidative stress, inhibit platelet aggregation, and improve insulin sensitivity and lipid profiles.
Luteolin has demonstrated neuroprotective effects that can be used to treat a range of neurological illnesses such as Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI). The compound can also easily penetrate the blood–brain barrier (BBB), decreasing the cytotoxic effects of oxidative stress and free radicals at the site of injury, which limits the inflammatory response after CNS injury.
Apigenin and luteolin's anti-inflammatory effects suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease. Microglia, the resident immune cells of the central nervous system, are thought to play a critical role in the etiology of various neurodegenerative diseases. Treatment of both N9 and murine-derived primary microglia cell lines with apigenin and luteolin significantly reduces CD40 expression induced by IFN-γ.
Apigenin treatment (25–50 mg/kg) for 2 weeks attenuated LPS-induced parkinsonism in experimental rats targeting TLR/NF-κB and Nrf2/HO-1 signaling pathways, reducing neuroinflammation in rat striatum as demonstrated by a significant decrease in TNF-α, IL-1β, and IL-6 expression, and reducing the nuclear translocation of phospho-NF-κB in the rat brain, exerting a neuroprotective effect. These data come from animal models, not human trials.
Traditionally recognized for their anti-inflammatory and antioxidant activities, both luteolin and apigenin have recently demonstrated the ability to inhibit cancer cell growth across multiple cancer types in vitro and in animal models. Reviews provide comprehensive summaries of in vivo evidence supporting the anticancer effects of luteolin and apigenin, highlighting their mechanisms of action. Reviewed studies encompass their effects on liver, lung, gastric, colon, breast, pancreatic, prostate, and skin cancers in animals.
Wogonin has beneficial effects on blood glucose level, insulin sensitivity, and lipid metabolism via selective PPARα and AMPK activation, without the adverse side effects of weight gain and fatty liver. The four main Scutellaria baicalensis flavonoids — baicalin, baicalein, wogonoside, and wogonin — have the effects of improving renal function, insulin resistance, and retinopathy of type 2 diabetic patients, though most such evidence comes from preclinical studies.
Although numerous studies have shown that flavones are absorbed systemically, they are typically found in plasma or urine as glucuronide or sulfate metabolites, rather than the original flavone O-glycosides. Flavones must first be hydrolyzed to aglycones for absorption and are then metabolized to glucuronidated or sulfated forms before reaching systemic circulation.
Apigenin when taken orally (whose bioavailability is about 30%) is systemically absorbed and recirculated by enterohepatic and local intestinal pathways.
A significant amount of the ingested flavonoids is not absorbed in the small intestine. They reach the large intestine and are degraded by colonic microflora into simple phenolic acids that are then absorbed into the circulatory system. These colonic catabolites are known to express biological activities and potential health properties relevant to flavonoids, although the ingested flavonoids primarily were not absorbed in the small intestine.
Flavonoid absorption, metabolism, and bioavailability are influenced by structural features, gut microbiota, and formulation strategies. Studies have reported poor bioavailability of flavonoid compounds in humans, which presents a major challenge for determining their optimal dosage, recommended intake, and, consequently, their therapeutic value.
More recent studies in the CNS system have indicated the presence of charged flavonoid conjugates in the brain and that these charged flavonoid molecules are biologically active, suggesting that research of flavonoids' bioavailability is moving into a new territory where CNS diseases can be the ultimate target of conjugated polyphenols.
Preclinical evidence (in vitro and animal models): Extensive. As described in Section 5.2, numerous cell-culture and animal studies demonstrate that luteolin and apigenin suppress major pro-inflammatory mediators including NF-κB, COX-2, iNOS, and multiple interleukins. Flavonoids are phytoconstituents with anti-inflammatory, antimutagenic, anticarcinogenic, and antimicrobial properties.
Human/clinical evidence: Many studies on the health benefits of flavonoids and other polyphenols have been tested using in silico, in vitro, and in vivo models; however, few studies have been carried out using clinical trials that have trustworthy subject sizes and are in accordance with clinical practice guidelines. The evidence base for flavones specifically in human anti-inflammatory trials is therefore limited and preliminary.
Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits, and berries, on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, with potential to prevent cardiovascular and neurodegenerative disease with a vascular component.
Evidence presented in human intervention reviews includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting cerebral blood flow (CBF) in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomized controlled trials conducted, and there is a clear need for further research.
Flavones, especially luteolin, protect against diabetic cardiomyopathy by activating antioxidant responses and inhibiting inflammation. This finding, however, comes primarily from animal studies.
There is increasing evidence that a diet rich in fruit and vegetables may be associated with a reduced risk of cardiovascular diseases. A meta-analysis of 9 cohort studies comprising more than 220,000 men and women showed that fruit and vegetable consumption was inversely associated with the risk of CVD. Such population-level data, while supportive, cannot be attributed exclusively to flavones.
Studies have revealed that flavonoids have neuroprotective effects and might reduce the risk of developing Alzheimer's disease, and higher intake of dietary flavonoids was also related to lower odds of frailty onset.
Previous research results have demonstrated that luteolin has good anti-inflammatory, anti-cancer, and antioxidant properties. Excitingly, luteolin has demonstrated neuroprotective effects that can be used to treat a range of neurological illnesses such as AD, PD, and traumatic brain injury.
Beneficial indications reported for apigenin in in vivo research include effects in diabetes, amnesia and Alzheimer's disease, depression and insomnia, and cancer. The preponderance of this evidence, however, is from animal models.
Evidence suggesting that some flavonoids or flavonoid-rich foods may enhance cognitive function is currently limited, and it is not yet known whether their consumption could lower the risk of cognitive impairments and dementia in humans.
Baicalin and baicalein, polyphenolic flavonoids derived from the root of Scutellaria baicalensis, evidently show potential in treating neurodegenerative diseases. Studies conducted prior to clinical trials have shown that they exert protective effects on the nervous system in different animal models. Mechanistic studies indicate that they exert anti-inflammatory effects by inhibiting pro-inflammatory cytokines, suppressing microglial activation, and regulating microglial phenotypes.
It is known that high intake of flavonoids from vegetables and fruits can be inversely associated with the risk of cancer. Epidemiological data have explored this association: Knekt et al. investigated the association between flavonoid (quercetin, kaempferol, myricetin, luteolin, and apigenin) intake and lung cancer, finding an inverse association between the intake of flavonoids and incidence of all sites of cancer, providing evidence of a protective role of flavonoids against lung cancer. This was an observational study and does not establish causation.
Despite the encouraging preclinical results, neither luteolin nor apigenin has yet been proven to be an effective agent against cancer in clinical trials. This underscores the current challenges in translating the promising anticancer effects of flavones into clinical success, emphasizing the need for further research using advanced animal models and appropriate administration routes.
Another limitation, if considering flavonoids as food supplements, is the toxicity of these compounds. Even if the beneficial properties of all these flavonoids are clear, it is important to consider that they have to pass clinical trials for efficacy and toxicity in humans.
Baicalein is one of the flavonoids with the highest content in Scutellaria baicalensis Georgi. Numerous studies have shown that baicalein has antidiabetic and insulin resistance effects. In a nutritionally obese rat model (fed with a high-fat diet), baicalein was shown to reduce fasting blood glucose, pancreatic β-cell apoptosis, and pancreatic β-cell dysfunction.
The four main flavonoids of Scutellaria baicalensis — baicalin, baicalein, wogonoside, and wogonin — have the effects of improving renal function, insulin resistance, and retinopathy of type 2 diabetic patients. Again, much of this evidence derives from preclinical studies, with clinical human data still limited.
Chamomile preparations are commonly used for gastrointestinal disorders, ulcers, and wounds. The flavone apigenin in chamomile is considered, along with other constituents such as chamazulene and alpha-bisabolol, to be among the active contributors to these effects. Apigenin and luteolin decrease inflammatory bowel disease markers by regulating TNF-α, IL-1β, iNOS, and COX-2 expression in preclinical models.
Flavones and flavonols are studied for their anti-inflammatory, antioxidant, and antibacterial activities, with research focused on discovering bioactive compounds and their mechanisms of action, anticipating that they can be used as standard treatment for inflammatory and infectious diseases in the future. The current evidence base for direct antimicrobial use in humans, however, is preclinical.
Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. A double-blind experiment on 58 healthy postmenopausal women, administering a daily dose of Epimedium prenylflavonoid extract (740 mg) or a placebo for 6 weeks, demonstrated that taking the drug was not associated with adverse symptoms, with no observed changes in liver, hematological, and renal parameters — though this study concerns prenylflavonoids rather than simple flavones per se.
Flavones are encountered in multiple supplemental and pharmaceutical forms, including standardized plant extracts (e.g., chamomile flower extract standardized to apigenin content, Scutellaria baicalensis root extract standardized to baicalin), isolated aglycone powders (apigenin, luteolin, chrysin, baicalein), glycoside forms (baicalin), and polymethoxylated flavone fractions from citrus.
In experimental rat studies, apigenin was tested at doses of 25–50 mg/kg for 2 weeks. This is an animal dose and cannot be directly extrapolated to humans.
A randomized, double-blind, placebo-controlled study investigated quercetin (a closely related flavonoid) at 500 mg/day in 50 women with rheumatoid arthritis, with inflammation, stiffness, and pain significantly reduced.
A double-blind clinical experiment administered Epimedium prenylflavonoid extract at a daily dose of 740 mg (or a placebo) for 6 weeks in postmenopausal women, one of the few human trials reporting a specific flavonoid-class dose.
Researchers are still uncertain whether the intake of single, individual polyphenols or a large combination of them (i.e., synergistic action) can produce the greatest health benefits for humans. Furthermore, studies have reported poor bioavailability of flavonoid compounds in humans, which presents a major challenge for determining their optimal dosage, recommended intake, and, consequently, their therapeutic value.
The components of Scutellaria baicalensis have limited clinical application due to their low water solubility, poor permeability, and microbial transformation in vivo. Nanopharmaceutical techniques can improve their biopharmaceutical properties, enhance their absorption in vivo, and improve their bioavailability. However, due to the limited number of clinical trials, doubts remain about their toxicity and improvements in human absorption as a result of nanoformulations.
High intakes of dietary flavonoids are generally regarded as safe, especially because of their low bioavailability. At the concentrations naturally present in a whole-food diet, flavones have a long history of consumption without documented adverse effects in the general population.
If flavonoids are given as dietary supplements, toxicity issues as well as nutrient-drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities.
Mixing prescription drugs with polyphenols has been reported to cause unfavorable drug-polyphenol interactions that lead to increased toxicity. The use of large amounts of concentrated flavonoids may pose public health concerns, as limited in vivo information is known about their adverse effects and their ability to interact with other drugs.
Flavonoids are substrates of enzymes like cytochrome P450 monooxygenases and phase II conjugation enzymes, as well as drug transporters involved in drug excretion, sharing the same metabolic pathways with many therapeutic drugs. A number of studies have demonstrated inhibition of various cytochrome P450 monooxygenases and drug transporters by flavonoids, and flavonoid-induced effects on drug bioavailability have been shown. This raises concerns about the safe use of flavonoid supplements and flavonoid-containing remedies.
Drugs with low bioavailability that undergo extensive CYP3A4 metabolism include anticancer drugs (everolimus); anti-infective agents (halofantrine, maraviroc); statins (atorvastatin, lovastatin, and simvastatin); cardioactive drugs (amiodarone, clopidogrel, dronedarone, eplerenone, ticagrelor); HIV protease inhibitors (saquinavir); immunosuppressants (cyclosporine, sirolimus, tacrolimus); antihistamines (terfenadine); and various CNS agents including selective serotonin reuptake inhibitors.
Because of the potential for adverse drug interactions, some clinicians recommend that people taking medications with low bioavailability (i.e., undergoing extensive metabolism by CYP3A4) avoid consuming grapefruit and grapefruit juice altogether during the treatment period.
In in vitro studies, flavonoids exhibited inhibitory effects on proteins which confer resistance to various conventional drugs, including ATP-binding cassette (ABC) efflux transporters such as P-glycoprotein and breast cancer resistance protein (BCRP).
Flavonoids can bind nonheme iron and thereby potentially reduce its dietary absorption. This interaction is of theoretical concern in individuals at risk of iron deficiency who consume very high doses of flavonoid supplements alongside iron-containing meals.
Safety is an important consideration that must be assessed through meticulous and extensive quality control testing, especially since supplements are not subject to the same stringent regulations as pharmaceuticals. Human studies, including randomized controlled trials, are required in order to provide clinical and scientific evidence regarding the safe and efficacious dose ranges for these products.
The overall health benefit of flavonoids is uncertain, and consumption of large quantities of them in fortified foods or supplements should not yet be encouraged without further human clinical data.
The scientific literature on flavones reflects a well-established preclinical profile — robust mechanistic and animal-model data demonstrating antioxidant, anti-inflammatory, neuroprotective, anticancer, and antidiabetic activity through multiple defined signaling pathways — but a substantially weaker and more heterogeneous body of evidence in humans. Recent clinical evidence suggests potential benefits of flavonoid-rich interventions on cognitive/neuroprotective outcomes, modulation of cardiometabolic risk, and inflammatory/immunometabolic endpoints, while heterogeneity in populations, dosage, matrices, and outcome selection limits comparability.
For specific flavones, the gap between the promise of in vitro and animal-model data and confirmed human benefit remains substantial. Despite the encouraging preclinical results, neither luteolin nor apigenin has yet been proven to be an effective agent against cancer in clinical trials. The same characterization applies broadly to most health claims made for isolated flavone compounds. Large, long-duration randomized trials testing apigenin or luteolin alone on hard clinical endpoints are lacking.
Health conditions that Flavones may help support.
Body systems that Flavones may help support.
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