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Has anyone tried 7,8-Dihydroxyflavone? (7,8 DHF)

Posted by PeterMartin on December 26, 2020, at 19:20:04

Has anyone tried "7,8 DHF"? (7,8-Dihydroxyflavone)

It's been talked about a lot on Reddit and there's a US based nootropics distributor that sells it now. Curious if anyone here has tried it for depression/anxiety/etc?
More info:

7,8-dihydroxyflavone (7,8-DHF) is a synthetic flavonoid that was initially discovered in a study screening for small molecules that could activate a particular receptor known as tropomyosin-related kinase B (TrkB), because the peptide produced in the human body that acts on this receptor, called brain derived neurotrophic factor (BDNF), could not be used due to poor absorption into the brain. 7,8-DHF was found to be a potent mimic of BDNF able to act on TrkB in a similar manner. This means that 7,8-DHF could theoretically cause similar effects as BDNF in the brain, and in theory be more therapeutically useful due to its better absorption and ability to cross the blood-brain barrier.

When the TrkB receptor is activated, neurons tend to experience growth and protective effects. The growth tends to affect the dendrites of the neuron which reach out into the synapse to communicate with subsequent neurons, and 7,8-DHF has shown an ability to promote the growth of these dendrites into the synapse to help restore communication between neurons in animal models of cognitive decline (Alzheimer's and aging being researched). Some other supplements such as bacopa monnieri and polygala tenuifolia tend to work via activating this receptor via releasing BDNF in the brain.

There is a possible nootropic use of this flavonoid in otherwise healthy subjects, but the cognitive benefits seen in cognitively unwell rodents may not correlate well to healthy subjects. The evidence to support its benefits in cognitive enhancement in healthy rodents is mixed, and no human evidence exists at all.

Due to 7,8-DHF being a simple and effective activator of TrkB which can cross the blood-brain barrier, it will likely continue being researched for its cognitive effects.
Wiki: Wiki:,8-Dihydroxyflavone
7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves.[2][3][4] It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB) (Kd ≈ 320 nM), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF).[5][6][7] 7,8-DHF is both orally bioavailable and able to penetrate the bloodbrain barrier.[8][9] A prodrug of 7,8-DHF with greatly improved potency and pharmacokinetics, R13 (and, formerly, R7), is under development for the treatment of Alzheimer's disease.[10][11]

7,8-DHF has demonstrated therapeutic efficacy in animal models of a variety of central nervous system disorders,[7] including depression,[8] Alzheimer's disease,[12][13][14] cognitive deficits in schizophrenia,[15] Parkinson's disease,[5] Huntington's disease,[16] amyotrophic lateral sclerosis,[17] traumatic brain injury,[18] cerebral ischemia,[19][20] fragile X syndrome,[21] and Rett syndrome.[22] 7,8-DHF also shows efficacy in animal models of age-associated cognitive impairment[23] and enhances memory consolidation and emotional learning in healthy rodents.[24][25] In addition, 7,8-DHF possesses powerful antioxidant activity independent of its actions on the TrkB receptor,[26] and protects against glutamate-induced excitotoxicity,[27] 6-hydroxydopamine-induced dopaminergic neurotoxicity,[28] and oxidative stress-induced genotoxicity.[29] It was also found to block methamphetamine-induced dopaminergic neurotoxicity, an effect which, in contrast to the preceding, was found to be TrkB-dependent.[30]

In 2017, evidence was published suggesting that 7,8-DHF and various other reported small-molecule TrkB agonists might not actually be direct agonists of the TrkB and might be mediating their observed effects by other means.[31][32]

7,8-DHF has been found to act as a weak aromatase inhibitor in vitro (Ki = 10 μM),[33] though there is evidence to suggest that this might not be the case in vivo.[5] In addition, it has been found to inhibit aldehyde dehydrogenase and estrogen sulfotransferase in vitro (Ki = 35 μM and 13 μM, respectively), though similarly to the case of aromatase, these activities have not yet been confirmed in vivo.[5] Unlike many other flavonoids, 7,8-DHF does not show any inhibitory activity on 17β-hydroxysteroid dehydrogenase.[34] 7,8-DHF has also been observed to possess in vitro antiestrogenic effects at very high concentrations (Ki = 50 μM).[35][36]

A variety of close structural analogues of 7,8-DHF have also been found to act as TrkB agonists in vitro, including diosmetin (5,7,3'-trihydroxy-4'-methoxyflavone), norwogonin (5,7,8-trihydroxyflavone), 4'-dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF), 7,8,3'-trihydroxyflavone, 7,3'-dihydroxyflavone, 7,8,2'-trihydroxyflavone, 3,7,8,2'-tetrahydroxyflavone, and 3,7-dihydroxyflavone.[37] The highly hydroxylated analogue gossypetin (3,5,7,8,3',4'-hexahydroxyflavone), conversely, appears to be an antagonist of TrkB in vitro.[37]




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