7,8-Dihydroxyflavone (Tropoflavin): Facts, Studies, Effects & Safety - Neuropedia

7,8-Dihydroxyflavone (Tropoflavin): Facts, Studies, Effects & Safety

Tropoflavin, or 7,8-dihydroxyflavone, is a plant-derived molecule that may mimic the effects of BDNF, an important molecule found in your brain and central nervous system.[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702337/

As of the time this was published, the majority of promising evidence in favor of tropoflavin comes from animal studies.[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702337/[3]https://www.sciencedirect.com/topics/medicine-and-dentistry/7-8-dihydroxyflavone There are no human studies of tropoflavin at this time.

Based on the current level of scientific interest in this compound, there’s a high likelihood that human trials will occur in the future. The results of future studies may be similar to studies using animals, or the results could be surprising and different.

Early evidence suggests the potential benefits may include: 

  • Memory support 
  • Protection of brain cells
  • Preservation of brain function
  • Balanced mood, and more.

Either way, you’ll be ahead of the curve after reading this educational guide. Here, you’ll find:

  • The origins of 7,8-dihydroxyflavone, or tropoflavin
  • Its mechanisms and how it appears to work
  • Effects and potential benefits according to studies
  • Safety and possible side effects, and
  • Frequently asked questions 

What Is 7,8-Dihydroxyflavone, or Tropoflavin?

7,8-dihydroxyflavone (7,8-DHF), also called tropoflavin, is a naturally occurring flavonoid found in plant species including Godmania aesculifolia, coatbuttons (tridax daisy), and primula tree leaves.[4]https://europepmc.org/article/PMC/5749600 7,8-DHF is currently under investigation in scientific studies because it may be able to mimic the effects of BDNF (brain-derived neurotrophic factor).[5]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702337/

Flavonoids are a class of polyphenol antioxidants that are found in nearly all fruits and vegetables. According to a 2016 paper published in the Journal of Nutritional Science, flavonoids are highly beneficial for health and are directly involved in many of the benefits of consuming fruits or vegetables.[6]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/ In the body, they typically exhibit antioxidant and anti-inflammatory properties, as well as the ability to balance the function of key cellular enzymes involved in many physiological processes.[7]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/

By isolating specific flavonoids like 7,8-DHF from plants, scientists are able to investigate the effects of these individual compounds on the body.[8]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/ Looking at individual compounds also allows for the possibility of consuming much higher amounts of individual flavonoids, in the form of dietary supplements, than would normally occur even in a diet high in fruits and vegetables. 

Researchers hold that 7,8-dihydroxyflavone potentially mimics the effects of BDNF brain-derived neurotrophic factor (BDNF).[9]https://pubmed.ncbi.nlm.nih.gov/20407211/

To understand why 7,8-DHF is an exciting compound in research, it’s helpful to keep in mind that BDNF, also known as the brain molecule, is responsible for repairing your brain, regenerating adult nerve cells, and maintaining brain cell connections.[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692714/[11]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/

Many scientists think BDNF expression may play an essential role in brain health, disease, and aging.[12]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713281/[13]https://www.frontiersin.org/articles/10.3389/fncel.2019.00363/full[14]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/ Achieving higher levels of BDNF might be a way to support cognitive function as well as the brain’s ability to heal itself, produce new neurons, and create synaptic connections.[15]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692714/[16]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/

For that matter, researchers also have investigated the effects of administering BDNF that was made outside of the body. Unfortunately, the results are disappointing — BDNF has a very short half-life when circulating through the body, and it doesn’t make its way past the blood-brain barrier.[17]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919955/

As a result, scientists began searching for molecules that could have similar effects to BDNF but offer a longer half-life and better properties for administration.[18]https://www.nature.com/articles/npp2011191

Tropoflavin is one such molecule. And early studies suggest that it might mimic the effects of BDNF in several important ways — or at least potentially offer comparable benefits.[19]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702337/

How Does Tropoflavin Work?

Most studies of tropoflavin assume that the majority of its effects are mediated through the TrkB pathway, which is the same pathway that BDNF uses.[20]https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-015-0048-7[21]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319242/ However, some evidence shows effects that occur independently of TrkB.[22]https://www.sciencedirect.com/science/article/abs/pii/S030439401100680X How to Pronounce TrkB:

TrkB signalling is “indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system” according to a 2013 paper in the International Journal of Molecular Science.[23]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676832/ Because tropoflavin was initially identified in a molecular library as binding to TrkB receptors, and because its effects resemble those of BDNF in many ways, it stands to reason that TrkB signalling could be involved in its effects. 

Other effects of tropoflavin may occur through non-TrkB pathways.[24]https://www.sciencedirect.com/science/article/abs/pii/S030439401100680X For example, a 2011 study found that tropoflavin protected a hippocampal cell line against toxicity caused by glutamate — and because the cell line didn’t have any TrkB receptors, the researchers concluded the most likely mechanism was due to antioxidant properties of tropoflavin.[25]https://www.sciencedirect.com/science/article/abs/pii/S030439401100680X

Recently, a few scientists have raised doubts that tropoflavin actually binds to TrkB receptors at all.[26]https://stke.sciencemag.org/content/10/493/eaal1670.full Taking into account molecule size, binding surfaces, and discrepancies between analytical techniques, this line of reasoning suggests it’s likely that all potential benefits of 7,8-DHF occur through different pathways that don’t directly resemble the mechanisms of action of BDNF after all.

For example, it’s possible tropoflavin activates TrkB signaling through a non-receptor pathway, or that all its effects are due to its antioxidants properties, or that an entirely different (undiscovered mechanism is involved instead.[27]https://stke.sciencemag.org/content/10/493/eaal1670.full

What Is 4′-Dimethylamino-7,8-dihydroxyflavone (Eutropoflavin)?

4′-Dimethylamino-7,8-dihydroxyflavone (4’DMA-7,8-DHF), also called eutropoflavin or R13, is a synthetic analog of 7,8-dihydroxyflavone that is structurally modified for a longer circulating half-life and greater potency.[28]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150605/

The two compounds have similar chemical formulas, but there are fewer studies of 4’DMA-7,8-DHF. According to the research team that developed it, 4’DMA-7,8-DHF is a precursor of 7,8-DHF that converts into 7,8-DHF during circulation in the body.[29]https://www.pnas.org/content/115/3/578

Available evidence suggests 4’DMA-7,8-DHF and 7,8-DHF work through the same or similar pathways as one another and have similar effects. Like 7,8-DHF, there are no human studies of 4’DMA-7,8-DHF yet.

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Effects and Potential Benefits of Tropoflavin

  • Memory and Cognitive Support
  • Balanced Mood
  • Energy Production
  • Neuroprotection and Neuroplasticity
  • Antioxidant Effects
  • Nrf2 Production
  • Gut Bacteria Support

Tropoflavin May Support Memory and Cognitive Function

According to a 2018 rodent study, through “activation of the BDNF-TrkB system”, 7,8-DHF “can improve basic behavioral tasks” including object recognition memory.[30]https://pubmed.ncbi.nlm.nih.gov/29500536/ The administration of 7,8-DHF also increased the density of dendritic spines, a measure of the connections associated with spatial learning.

A separate 2012 study found that 7,8-dihydroxyflavone rescues spatial memory and synaptic plasticity in rats with cognitive impairment due to aging.[31]https://pubmed.ncbi.nlm.nih.gov/22694088/

Tropoflavin May Support a Balanced Mood

In a 2016 study, researchers found that tropoflavin rapidly supported a balanced mood in rats exposed to chronic mild stress.[32]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067348/

Other research suggests tropoflavin may support adaptive emotional learning.[33]https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2010.10030326[34]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770732/

Tropoflavin May Support Energy Production

A 2018 mouse study found that tropoflavin treatment increased cellular respiration (the creation and use of energy in cells) through mitochondrial biogenesis (increasing the number of mitochondria, the “powerhouse of the cell”).[35]https://pubmed.ncbi.nlm.nih.gov/29935237/ As a result, in obese mice, tropoflavin reduced body weight gain and reversed markers of poor metabolic health. 

Tropoflavin May Support Neuroprotection and Neuroplasticity

Tropoflavin may act as a BDNF mimetic, which means it could have similar effects to BDNF, including supporting neuroprotection (protecting the structure or function of neurons against damage) and neuroplasticity (the brain’s ability to learn or change by reorganizing neural connections).[36]https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113397

Researchers are investigating tropoflavin for potential applications in traumatic brain injuries (TBI) as well as neurodegenerative conditions like Alzheimer’s.[37]https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113397[38]https://pubmed.ncbi.nlm.nih.gov/29510124/

Because research to date has involved animal subjects, it’s not possible yet to say whether these potential benefits will apply to humans.

Tropoflavin May Act as an Antioxidant 

Like all flavonoids, tropoflavin is an antioxidant.[39]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/ Antioxidants work by inhibiting oxidation and oxidative stress, which involve the loss of electrons from molecules and the production of damaging free radicals in the body.

A 2011 in vitro cell study found that tropoflavin acted as an antioxidant that helped protect brain cells from damage, increased cellular glutathione levels, and reduced the production of reactive oxygen species (ROS).[40]https://www.sciencedirect.com/science/article/abs/pii/S030439401100680X

7,8-Dihydroxyflavone May Support Nrf2 Production 

According to a 2015 in vitro study, tropoflavin “augments the cellular antioxidant defense capacity through activation of the Nrf-2/HO-1 pathway”.[41]https://pubmed.ncbi.nlm.nih.gov/26096841/

Nuclear factor erythroid 2 (NFE2)-related factor 2, Nrf2 for short, is an important part of your body’s antioxidant defense system, and compounds that boost or activate Nrf2 can help protect animals from oxidative damage.[42]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680839/   

Other flavonoids, such as curcumin, also appear to offer neuroprotective and antioxidant benefits through the Nrf2 pathway.[43]https://pubmed.ncbi.nlm.nih.gov/29571711/

7,8-Dihydroxyflavone May Support a Balanced Microbiome

In a study published in 2021 in the journal Nutrients, beneficial metabolic effects of tropoflavin on female mice were linked to an increase in diversity of gut bacteria and reduced populations of pro-inflammatory species thought to cause obesity, particularly Desulfovibrionaceae.[44]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920311

And according to a 2020 paper on flavonoids and gut health, flavonoids and their metabolites “can shape gut microbiota by inhibiting the growth of various pathogens and increasing beneficial genera such as Bifidobacterium and Lactobacillus”.[45]https://www.sciencedirect.com/science/article/pii/S0958166919301569 In other words, flavonoids (and other polyphenols) can act as prebiotics.

Tropoflavin Side Effects and Safety

There are no human trials of tropoflavin at this time. As with most of the effects of tropoflavin, any information on safety or side effects is provisional and comes from studies using animal models.

According to existing evidence and current scientific perspectives, there appears to be a low risk of adverse effects from tropoflavin.

The authors of a 2018 paper published in the U.S. Proceedings of the National Academy of Sciences referred to the safety profile of tropoflavin as “favorable”.[46]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777001/

A 2016 study published in Scientific Reports concluded that “Long-term oral administration of 7, 8-DHF is safe for monkeys”.[47]https://www.nature.com/articles/srep34339 The study found no demonstrable toxicity at doses of 30 milligrams per kilogram (equivalent to a human dosage of 9.72 mg/kg when accounting for species differences in body surface area) after 7 months of treatment.[48]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

In an in vitro study, 7,8-DHF potentiated (enhanced) epilepsy-like electrical activity in mouse brain slices.[49]https://www.sciencedirect.com/science/article/abs/pii/S0304394019301685 It did not cause seizure-like activity, but enhanced discharge activity associated with seizures. As a result, people with epilepsy or seizure disorders should approach 7,8-DHF with caution.

Tropoflavin may interact with prescription drugs. Like other flavonoids, it’s highly reactive with other molecules and compounds. Evidence suggests that 7,8-DHF may alter the action of CYP450 liver enzymes. That could alter the metabolism of some drugs in your body.[50]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920897/

Always speak to your doctor about any dietary supplements before you take them, especially if you have a medical condition or take prescription drugs.

Frequently Asked Questions (FAQs) About 7,8-Dihydroxyflavone, or Tropoflavin

Is Tropoflavin a Nootropic?

Nootropics, also called smart drugs, are compounds or supplements that support cognitive performance or brain function.[51]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021479/Preliminary evidence in animal studies suggests, but does not prove, that 7,8-dihydroxyflavone has nootropic activity†. In the absence of human trials, no one can say for certain.

What’s the Difference Between Tropoflavin and BDNF?

Your body produces BDNF (brain-derived neurotrophic factor) naturally, but does not produce tropoflavin. Tropoflavin is only found in a few plant species. Scientists consider tropoflavin to be a BDNF mimetic because it binds to the same cellular receptor (TrkB) and may have similar beneficial effects†.[52]https://pubmed.ncbi.nlm.nih.gov/29935237/

Also, according to a 2017 paper published in Neural Regeneration Research.[53]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319242/,

Compared to BDNF, tropoflavin has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application†.

Does Tropoflavin Support Weight Loss?

A 2015 study found that if tropoflavin or 7,8-dihydroxyflavone supports weight loss, it may work for females but not males†.[54]https://pubmed.ncbi.nlm.nih.gov/25754472/ Researchers discovered 7,8-DHF boosted metabolism and decreased fat in female rats only. As with other effects of 7,8-DHF, these findings may not apply to humans.

Other preliminary evidence suggests that tropoflavin may support weight loss by supporting gut bacteria or by supporting the function of mitochondria†.[55]https://pubmed.ncbi.nlm.nih.gov/33669347/[56]https://pubmed.ncbi.nlm.nih.gov/29935237/

Does Tropoflavin Cause Hair Loss (or Support Hair Growth)? 

There’s no direct evidence to suggest that tropoflavin has any effect on hair growth or hair loss. But, a 1999 paper in an experimental biology journal speculated that BDNF and other compounds that stimulate brain cell growth might play a role in controlling hair growth based on data from rodents†.[57]https://pubmed.ncbi.nlm.nih.gov/9973328/According to a 2017 paper, Japanese researchers discovered that bioactive compounds in Panax ginseng (Asian or Korean ginseng) may inhibit the ability of BDNF from binding to the TrkB receptors of hair follicles, which could be helpful for people with hair loss†.[58]https://www.jstage.jst.go.jp/article/bpb/40/10/40_b17-00205/_pdf

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