HA4822 7,8-Dihydroxyflavone hydrate Powder (CAS: 38183-03-8)

7,8-Dihydroxyflavone Description

7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavone found in the leaves of Godmania aesculifolia, Tridax procumbens, and primrose trees. It has proven to be a potent and selective low-molecular-weight agonist of the Tropomyosin receptor kinase B (TrkB), which is the primary signaling receptor for the neurotrophic factor BDNF (Brain-Derived Neurotrophic Factor). 7,8-DHF is both orally bioavailable and capable of crossing the blood-brain barrier.

7,8-Dihydroxyflavone Specifications

7,8-Dihydroxyflavone Applications

7,8-Dihydroxyflavone has demonstrated therapeutic efficacy in animal models for various central nervous system disorders, including depression, Alzheimer's disease, cognitive deficits in schizophrenia, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, traumatic brain injuries, cerebral ischaemia, fragile X syndrome, and Rett syndrome. 7,8-DHF also shows efficacy in animal models for age-related cognitive impairments and improves memory consolidation and emotional learning in healthy rodents.

Moreover, 7,8-Dihydroxyflavone, independent of its effect on the TrkB receptor, possesses strong antioxidant activity and protects against glutamate-induced excitotoxicity, 6-hydroxydopamine-induced dopaminergic neurotoxicity, and oxidative stress-induced genotoxicity. It has also been found to block methamphetamine-induced dopaminergic neurotoxicity, an effect which has been shown to be TrkB-dependent.

7,8-Dihydroxyflavone has proven to be a viable therapeutic option for traumatic brain injuries and various degenerative neurological disorders. By activating the TrkB receptor and downstream signalling pathways, it promotes neuronal survival and dendritic integrity, reduces injury-induced tissue damage, and improves motor and cognitive dysfunction. Its ability to cross the blood-brain barrier and its broad therapeutic potential, including a possible anti-inflammatory effect in the central nervous system, makes it a valuable compound deserving further investigation for its application in traumatic brain injuries and other neurological conditions in clinical settings.

The BDNF-mimetic compound 7,8-Dihydroxyflavone (7,8-DHF), a potent low-molecular-weight TrkB agonist, displays significant therapeutic efficacy against Alzheimer’s disease (AD). However, 7,8-DHF has only modest oral bioavailability and a limited pharmacokinetic (PK) profile. To overcome these preclinical obstacles, we employed a prodrug strategy to enhance the oral bioavailability of 7,8-DHF and brain exposure, identifying the optimal prodrug R13, which exhibited favourable properties and dose-dependently reversed cognitive deficits in an AD mouse model. We synthesised a significant number of 7,8-DHF derivatives by modifying the ester or carbamate group at the catechol ring of the parent compound. Through in vitro absorption, distribution, metabolism, and excretion tests combined with in vivo PK studies, we identified a prodrug, R13, that markedly upregulated the PK profiles of 7,8-DHF. Chronic oral administration of R13 activated the TrkB signalling pathway and prevented Aβ deposition in 5XFAD AD mice, inhibiting the pathological cleavage of APP and Tau via AEP. Additionally, R13 inhibited synaptic loss in the hippocampus and dose-dependently improved memory deficits. These results suggest that the prodrug R13 is an optimal therapeutic agent for the treatment of Alzheimer’s disease.

References

J. Romeika, M. Wurzelmann, D. Sun: Chapter 14 - The TrkB Receptor Agonist 7,8-Dihydroxyflavone and Its Therapeutic Potential in Traumatic Brain Injury. New Therapeutics for Traumatic Brain Injury - Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration 2017, pages 225-234

Chun Chen, Zhihao Wang, Zhentao Zhang, Xia Liu, Seong Su Kang, Ying Zhang, and Keqiang Ye: The Development of a Prodrug of 7,8-Dihydroxyflavone and Its Therapeutic Efficacy for the Treatment of Alzheimer’s Disease. https://doi.org/10.1073/pnas.1718683115

[1] https://en.wikipedia.org/wiki/7,8-Dihydroxyflavone#cite_note-pmid29295929-10

[2] J. Romeika, M. Wurzelmann, D. Sun: Chapter 14 - The TrkB Receptor Agonist 7,8-Dihydroxyflavone and Its Therapeutic Potential in Traumatic Brain Injury. New Therapeutics for Traumatic Brain Injury - Prevention of Secondary Brain Damage and Enhancement of Repair and Regeneration 2017, pages 225-234

[3] Chun Chen, Zhihao Wang, Zhentao Zhang, Xia Liu, Seong Su Kang, Ying Zhang, and Keqiang Ye: The Development of a Prodrug of 7,8-Dihydroxyflavone and Its Therapeutic Efficacy for the Treatment of Alzheimer’s Disease. https://doi.org/10.1073/pnas.1718683115