Can 7,8-Dihydroxyflavone Be Used To Treat Neurodegenerative Diseases?

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Can 7,8-Dihydroxyflavone Be Used To Treat Neurodegenerative Diseases?

7,8-DIHYDROXYFLAVONE History 7,8-Dihydroxyflavone (7,8-DHF) is a synthetic flavonoid that was originally discovered in a study to screen small molecules that can activate what is called tropomyosin-related kinase B ( The specific receptor of TrkB) is called brain-derived neurotrophic factor (BDNF) in the human body that acts on this receptor, and it cannot be used due to malabsorption of the brain. 7,8-DHF was found to be an effective mimic of BDNF and can act on TrkB in a similar way. This means that 7,8-DHF can theoretically produce similar effects to BDNF in the brain, and is theoretically more useful for treatment due to its better absorption and ability to cross the blood-brain barrier.

What is 7,8-DIHYDROXYFLAVONE(38183-03-8) Powder?

7,8-dihydroxyflavone, also known as the 7,8-DHF or Tropoflavin, which is a naturally occurring flavonoid produced by several plants, including the weed Tridax procumbens (coalbuttons or tridax daisy) and the tree Godmania aesculifolia. In animal models, 7,8-DHF has shown efficacy against several diseases of the nervous system, including Alzheimer's, Parkinson's, and Huntington's. It has a role as a plant metabolite, a

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tropomyosin-related kinase B receptor agonist, an antidepressant, an antioxidant and an antineoplastic agent.

As a mimic of the agonist of tropomyosin receptor kinase B (TrkB) affecting brain-derived neurotrophic factor (BDNF), after 7,8-dihydroxyflavone binds to the TrkB receptor, the signaling cascade is initiated, Can promote neuron survival and regeneration.

7,8-DHF also has a protective effect on cell apoptosis. It can cross the blood-brain barrier and directly act on the brain TrkB receptors; this cannot be achieved by peripheral injection of BDNF. Therefore, it is a very promising natural compound with cognitive functions.

In addition, 7, 8-DHF has oral biological activity, and exerts its neurotrophic activity in the central nervous system by penetrating the brain blood barrier (BBB).

7,8-DIHYDROXYFLAVONE Mechanism Of Action 7,8-DHF mimics the effects of brain-derived neurotrophic factor (BDNF) in brain cells by activating tropomyosin-related kinase B (TrkB) receptors, the typical target of BDNF. The therapeutic potential of BDNF is restricted due to its short half-life (less than 10 minutes) and its inability to cross the blood-brain barrier because of its large size. Unlike BDNF 7,8-DHF is able to penetrate the blood-brain barrier and enter the central nervous system (CNS).

7,8-DHF also increases the production of Nrf2. Nrf2 increases antioxidants enzymes such as heme oxygenase 1 (HO-1) and also enzymes that repair DNA (8-oxoguanine DNA glycosylase-1 – OGG1).

The Benefits of 7,8-DIHYDROXYFLAVONE There are some potential benefits of7,8-DIHYDROXYFLAVONE powder: 1) Memory, Learning and Cognitive Support 2) Balanced Mood 3) Energy Production 4) Neuroprotection and Neuroplasticity 5) Antioxidant Effects (Anti-Inflammation) 6)Nrf2 Production 7)Gut Bacteria Support Also, 7,8-DHF elicits protection in scopolamine induced Alzheimer-like pathologic dysfunction.

7,8-DIHYDROXYFLAVONE Dosage As a dietary supplement, take one to two 25mg capsules of 7,8 Dihydroxyflavone daily. It appears to be subject to extensive first-pass metabolism in the liver. Due to improved bioavailability, sublingual administration (under the tongue) may be preferred.

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More Information 7,8-DHF has demonstrated therapeutic efficacy in animal models of various central nervous system disorders, including depression, Alzheimer's disease, cognitive disorders such as schizophrenia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral ischemia, fragile X syndrome , and Rett syndrome . 7,8-DHF also shows activity in animal models of age-related cognitive impairment and improves memory consolidation and emotional learning in healthy rodents. In addition, 7,8-DHF has potent antioxidant activity independent of its effects on the TrkB receptor, and glutamate-induced excitotoxicity, 6-hydroxydopamine-induced dopaminergic neurotoxicity, and oxidative stress-induced genotoxicity. It was also found to block methamphetamine-induced dopaminergic neurotoxicity, an effect found to be TrkB-dependent unlike the previous one.

In 2017, evidence was published showing that 7,8-DHF and various other reported small molecule TrkB agonists may not actually be direct agonists of TrkB and may mediate its observed effects in other ways.

7,8-DHF was found to act as a weak inhibitor of aromatase in vitro (Ki = 10 µM) although there is evidence to suggest that it may not be the case for vivo. In addition, it has been found to inhibit aldehyde dehydrogenase and estrogen sulfotransferase in vitro (Ki = 35 µM and 1-3 µM, respectively), yet similarly to the aromatase state, these activities have not yet been confirmed in vivo. Unlike many other flavonoids, 7,8-DHF does not show any inhibitory activity on 17β-hydroxysteroid dehydrogenase. 7,8-DHF has also been observed to have in vitro antiestrogenic effects (at very high concentrations of K = 50 µM).

Various structural analogs of close 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, eutropoflavin), 7,8,3'-trihydroxyflavone, 7,3'-dihydroxyflavone, 7,8,2'-trihydroxyflavone, 3 ,7,8,2'-tetrahydroxyflavone and 3,7-dihydroxyflavone. The highly hydroxylated analog gossypetin (3,5,7,8,3', 4'-hexahydroxyflavone), in contrast, appears to be an antagonist of TrkB in vitro.

Reference: [1]Johnson RA, Lam M, Punzo AM, Li H, Lin BR, Ye K, Mitchell GS, Chang Q (2012). "7,8-dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome". J. Application Fizol . 112(5): 704–10. doi: 10.1152/japplphysicol.01361.2011 . PMC 3643819 . PMID 22194327 .

[2]Zeng Y, Lv F, Li L, Yu H, Dong M, Fu Q (2012). "7,8-dihydroxyflavone rescues spatial memory and synaptic plasticity in cognitively impaired aged rats". J. Neurochem. 122 (4): 800–11. doi: 10.1111/j.1471-4159.2012.07830.x . PMID 22694088.

[3]Zeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (2013). "Small molecules activating the TrkB receptor for the treatment of various CNS disorders". CNS Neurone Disorder Drug Targets . 12 (7): 1066–77. doi: 10.2174/18715273113129990089 . PMID 23844685.

[4]Latha Devi & Masuo Ohno. 7,8-Dihydroxyflavone, a Small-Molecule TrkB Agonist, Reverses Memory Deficits and BACE1 Elevation in a Mouse Model of Alzheimer's Disease. Neuropsychopharmacology volume 37, pages434–444 (2012).2011;9:7.

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[5]Chaoyang Liu, Chi Bun Chan, and Keqiang Ye. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener. 2016; 5: 2. doi: 10.1186/s40035-015-0048-7. PMCID: PMC4702337

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