7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

Abstract

: 7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.

The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice

“…More importantly, our results of subchronic systemic administration of 7,8-DHF highlight the BDNF-TrkB pathway as the potential therapeutic targets for the treatment of cognitive deficits in stress-related psychiatric disorders. Currently, clinical drug development of 7,8-DHF faces several challenges, e.g., low oral bioavailability (see [ 32 ] for a review), but also makes great progress in preclinical studies (e.g. [ 57 ]).…”

Multisensory Fusion Training and 7, 8-Dihydroxyflavone Improve Amyloid-β-Induced Cognitive Impairment, Anxiety, and Depression-Like Behavior in Mice Through Multiple Mechanisms

“…It is often used as a TrkB receptor agonist to mimic BDNF expression, and its oral efficacy has been confirmed in animal experiments. 36 , 37 MSFT and DHF intervene in AD from different perspectives, and their combined use can comprehensively utilize their advantages and enhance treatment effectiveness. MSFT can promote neurogenesis by stimulating neural network connections, while DHF can provide neuroprotection and proliferation.…”

Impact of dietary plant flavonoids on 7,8‐dihydroxyflavone transepithelial transport in human intestinal Caco‐2 cells

“…Among them, the activation of MAPK/ERK pathway can stimulate neural differentiation, PI3K/Akt pathway can promote neuron survival and growth, while PLCγ1/PKC signaling is crucial for synaptic plasticity. Currently, 7,8‐DHF is being studied for its potential preventative and therapeutic applications in various BDNF/TrkB signal‐related diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Rett syndrome, depression, and metabolic syndrome (Chen et al, 2018 , 2021 ; Paul et al, 2021 ; Yang & Zhu, 2022 ; Zhao et al, 2021 ). However, natural plant flavonoids generally have low oral bioavailability.…”