7,8-DHF: Strong in Mice, Untested in People
7,8-Dihydroxyflavone (tropoflavin) was reported in 2010 as a small molecule that switches on TrkB, the receptor for the brain growth factor BDNF. Hundreds of lab papers followed. No human trial has.
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How Does 7,8-DHF Work?
Jang and colleagues at Emory (PNAS 2010) reported 7,8-DHF as a high-affinity TrkB agonist that triggers receptor dimerization and autophosphorylation. It protected normal neurons, but not TrkB-deficient ones, from apoptosis, and in mice it reduced stroke infarct volume and was neuroprotective in a Parkinson disease model.
A Columbia and Broad Institute team (Science Signaling 2017) built quantitative assays for TrkB activation, downstream signaling and gene expression. BDNF gave robust, dose-dependent activation. The reported small-molecule TrkB agonists, 7,8-DHF among them, did not, and the authors called for results with these compounds to be read carefully.
A 2024 eLife study found 7,8-DHF binds and reversibly inhibits pyridoxal phosphatase (PDXP), the enzyme that breaks down active vitamin B6, with sub-micromolar potency. In mouse hippocampal neurons it raised active B6 levels through PDXP. The authors present this as one explanation for the debate over how 7,8-DHF acts.
In test-tube work (Biomolecules 2019), 7,8-DHF bound tightly to serum albumin and potently inhibited CYP2C9, CYP2C19, CYP3A4 and xanthine oxidase. The authors warn that taking it with medicines could cause pharmacokinetic interactions.
What the Data Shows
Key Takeaways
- Emory researchers reported 7,8-DHF in 2010 as a TrkB agonist that imitates BDNF in cells and mice (PMID 20133810).
- Several rodent studies report memory gains, including object memory in healthy rats and spatial memory in Alzheimer-model mice (PMID 24070857, 24022672).
- The animal results are not unanimous: in APP23/PS45 Alzheimer-model mice it did not reduce plaques or improve learning and memory (PMID 25523427).
- Oral bioavailability is modest, which led the original lab to develop the prodrug R13 (PMID 29295929).
- In neonatal mice, brain levels reached only about 9-10% of plasma levels, and more than 95% left the plasma within 3 hours (PMID 39881861).
- In vitro it inhibits CYP2C9, CYP2C19 and CYP3A4, enzymes that clear many prescription drugs (PMID 31731555).
- Any effect in humans. There are no registered trials and no clinical-trial papers.
- Whether it truly activates TrkB. An independent 2017 assay panel could not reproduce that activity.
- Which mechanism drives the animal results: TrkB, PDXP inhibition, antioxidant activity, or its O-methylated metabolites.
- A human dose, and long-term safety at any dose.
- Whether sex-dependent results in mice, such as the obesity protection reported in female mice (PMID 25754472), apply to people.
Frequently Asked Questions
What is 7,8-DHF?
7,8-Dihydroxyflavone (7,8-DHF), also called tropoflavin, is a flavone, a type of plant flavonoid. In 2010 an Emory University team reported that it activates TrkB, the receptor for the brain growth factor BDNF (PMID 20133810). It is sold online as a nootropic research compound and has no approved medical use.
Does 7,8-DHF improve memory?
Only animal data exist. Rodent studies report better object and spatial memory, including in Alzheimer-model mice (PMID 24070857, 24022672). Another group found no memory or plaque benefit in a different Alzheimer mouse model (PMID 25523427). No study has tested memory in people, so any human benefit is unknown.
Does 7,8-DHF really activate the BDNF receptor?
This is disputed. The 2010 discovery paper reported strong TrkB activation, but a 2017 Science Signaling study using quantitative assays could not reproduce it for 7,8-DHF or other reported small-molecule TrkB agonists (PMID 28831019). A 2024 eLife paper found it also inhibits pyridoxal phosphatase, a vitamin B6 enzyme (PMID 38856179).
Is 7,8-DHF safe to take with other medications?
There are no human safety data. In test-tube studies 7,8-DHF potently inhibited the liver enzymes CYP2C9, CYP2C19 and CYP3A4 and bound strongly to albumin (PMID 31731555). The authors warn this could change blood levels of drugs taken alongside it. Anyone on prescription medicines should raise this with a clinician first.
What is 4'-DMA-7,8-DHF?
4'-Dimethylamino-7,8-dihydroxyflavone is a synthetic derivative made by the same Emory group. In their 2010 Journal of Medicinal Chemistry paper it showed higher TrkB agonist activity than 7,8-DHF and a longer-lasting TrkB activation effect in animals (PMID 21073191). Like the parent compound, it has no human data.
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7,8-DHF has no approved medical use and no human trials; nothing on this page is a dosing recommendation.
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