7,8-Dihydroxyflavone and its Therapeutic Potentials

7,8-Dihydroxyflavone (7,8-DHF) is a bioactive flavonoid compound that acts as a selective agonist for the tyrosine kinase receptor B (TrkB). TrkB is typically activated by brain-derived neurotrophic factor (BDNF), playing critical roles in neuron survival, differentiation, synaptic plasticity, and neurogenesis. Since BDNF has poor pharmacokinetics which limit its therapeutic use, 7,8-DHF serves as an effective mimic, activating downstream signaling pathways and protecting neurons from apoptosis.

Neuroprotective Actions

In various mouse models, 7,8-DHF demonstrated neuroprotective properties by activating TrkB. It showed potential in protecting against kainic acid-induced toxicity, reducing stroke-induced brain damage, and providing neuroprotection in Parkinson's disease models. These findings position 7,8-DHF as a potent therapeutic candidate for treating neurological disorders.

Antidepressant Effects

Research indicates that both 7,8-DHF and its synthetic derivatives are orally bioavailable TrkB agonists with potent antidepressant properties. These compounds promote neurogenesis in the brain, especially in the dentate gyrus, and exhibit notable antidepressant effects, suggesting potential therapeutic benefits in treating depression.

Cognitive Enhancements

In studies involving aged rats with cognitive decline, 7,8-DHF improved spatial memory and synaptic plasticity. It reversed cognitive impairments in rats, with more pronounced benefits observed in younger rats, supporting early intervention in cognitive aging.

Addressing Cognitive Deficits in Schizophrenia

7,8-DHF was found to enhance TrkB activation and hippocampal synaptic plasticity, leading to improvements in spatial working memory in rat models of schizophrenia. This suggests that activating TrkB signaling could potentially reverse cognitive deficits associated with the condition.

Effects on Emotional Learning

Systemic administration of 7,8-DHF activated TrkB receptors in the amygdala and enhanced both the learning and extinction of fear responses in mice. This points to therapeutic implications for treating learning deficits associated with stress and psychological conditions.

Therapeutic Strategy for Alzheimer's Disease

Treatment with 7,8-DHF resulted in significant improvement in spatial memory and synaptic plasticity in mouse models of Alzheimer's disease (AD), suggesting chronic activation of TrkB signaling as a viable approach for cognitive function enhancement in AD.

Antioxidant Activity

7,8-DHF also exhibits antioxidant properties, protecting cells from oxidative stress-induced DNA damage by activating DNA repair systems and enhancing the expression of antioxidant enzymes.

Conclusions

The collective research on 7,8-DHF underscores its potential as a therapeutic agent due to its ability to mimic BDNF, activate TrkB signaling, and exert neuroprotective, antidepressant, and cognitive-enhancing effects. Its antioxidant activity and potential to address a variety of neurological conditions make it a promising candidate for further drug development and clinical trials.

References:

1. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
2. A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect
3. 7,8-dihydroxyflavone rescues spatial memory and synaptic plasticity in cognitively impaired aged rats
4. Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia
5. Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning
6. 7,8-Dihydroxyflavone, a small molecule TrkB agonist, improves spatial memory and increases thin spine density in a mouse model of Alzheimer disease-like neuronal loss
7. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease
8. Towards tropomyosin-related kinase B (TrkB) receptor ligands for brain imaging with PET: radiosynthesis and evaluation of 2-(4-[(18)F]fluorophenyl)-7,8-dihydroxy-4H-chromen-4-one and 2-(4-([N-methyl-(11)C]-dimethylamino)phenyl)-7,8-dihydroxy-4H-chromen-4-one
9. Effect of 7, 8-dihydroxyflavone on the up-regulation of Nrf2-mediated heme oxygenase-1 expression in hamster lung fibroblasts
10. A perspective on dietary phytochemicals and cancer chemoprevention: oxidative stress, nrf2, and epigenomics
11. 7,8-Dihydroxyflavone suppresses oxidative stress-induced base modification in DNA via induction of the repair enzyme 8-oxoguanine DNA glycosylase-1
12. Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity
13. Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity
14. Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8-dihydroxyflavone active in mouse models of depression
15. Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytes
16. Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment
17. Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters
18. The lighter side of BDNF
19. Neurotrophin signal transduction in the nervous system
20. TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor
21. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance
22. 7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease
23. 7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease
24. BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses
25. 7,8-dihydroxyflavone ameliorates scopolamine-induced Alzheimer-like pathologic dysfunction
26. In vivo optical signatures of neuronal death in a mouse model of Alzheimer's disease
27. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves
28. Induction of a distinct morphology and signal transduction in TrkB/PC12 cells by nerve growth factor and brain-derived neurotrophic factor
29. 7,8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine
30. Effects of TrkB agonist 7,8-dihydroxyflavone on sensory gating deficits in mice after administration of methamphetamine
31. 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-κB and MAPK signaling pathways
32. 7,8-Dihydroxyflavone exhibits anti-inflammatory properties by downregulating the NF-κB and MAPK signaling pathways in lipopolysaccharide-treated RAW264.7 cells
33. Role of accumbens BDNF and TrkB in cocaine-induced psychomotor sensitization, conditioned-place preference, and reinstatement in rats
34. Infralimbic BDNF/TrkB enhancement of GluN2B currents facilitates extinction of a cocaine-conditioned place preference
35. TrkB receptor agonist 7, 8 dihydroxyflavone triggers profound gender- dependent neuroprotection in mice after perinatal hypoxia and ischemia
36. BDNF protects against spatial memory deficits following neonatal hypoxia-ischemia
37. 7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats
38. The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal Newborn Neuron Death After Traumatic Brain Injury
39. 7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats
40. Activation of BDNF signaling prevents the return of fear in female mice
41. Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression
42. Activation of TrkB by 7,8-dihydroxyflavone prevents fear memory defects and facilitates amygdalar synaptic plasticity in aging
43. Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging
44. 7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice
45. No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes
46. Vasorelaxing and antihypertensive effects of 7,8-dihydroxyflavone
47. Characteristics of BDNF-induced weight loss
48. BDNF function and intracellular signaling in neurons
49. Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF
50. Protection of spiral ganglion neurons from degeneration using small-molecule TrkB receptor agonists
51. Activation of muscular TrkB by its small molecular agonist 7,8-dihydroxyflavone sex-dependently regulates energy metabolism in diet-induced obese mice
52. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF
53. Neurotrophin-4 couples to locally modulated ACh release at the end of neuromuscular synapse maturation
54. The interaction between tropomyosin-related kinase B receptors and presynaptic muscarinic receptors modulates transmitter release in adult rodent motor nerve terminals
55. The novel TrkB receptor agonist 7,8-dihydroxyflavone enhances neuromuscular transmission
56. Nuclear organization and chromatin dynamics--Sp1, Sp3 and histone deacetylases
57. The role of Sp1 and Sp3 in normal and cancer cell biology
58. Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1
59. Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C
60. Intervention with 7,8-dihydroxyflavone blocks further striatal terminal loss and restores motor deficits in a progressive mouse model of Parkinson's disease
61. Tyrosine hydroxylase
62. Overview of tyrosine hydroxylase in Parkinson's disease
63. 7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis
64. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3
65. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression
66. 7,8-dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome

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