- 7,8-Dihydroxyflavone is an antioxidant naturally abundant in plants that activates the Trk B receptor in the central nervous system (CNS), mimicking the effects of brain-derived neurotrophic factor (BDNF)
- End-use is limited to non-clinical scientific research. This product is not a dietary supplement.
7,8-DHF is a plant-derived flavone found in Tridax procumbens and primula tree leaves. Flavones and Flavonoids in general (e.g., those derived from blueberries) have robust neuroprotective effects and improve cognitive performance in both humans and animal models.
7,8-dihydroxyflavone is a small molecule that potently and selectively activates one of the brain-derived neurotrophic factor (BDNF) receptors in the brain, referred to as TrkB. Hence, 7,8-dihydroxyflavone is said to be a “Trk B agonist.” 7,8-dihydroxyflavone activates this endogenous receptor for BDNF by triggering receptor dimerization and autophosphorylation, presumably by inducing a conformation change in the protein.
Because 7,8-dihydroxyflavone activates the same receptor as BDNF, 7,8-DHF may theoretically elicit similar effects to BDNF itself in the brain. 7,8-DHF is likely to prove more useful therapeutically than BDNF due to its superior bioavailability and blood brain barrier permeability.
Generally speaking, augmenting BDNF/Trk B signaling remains a promising therapeutic strategy for reversing cognitive deficits in neurodegenerative disease.
Brain Derived Neurotrophic Factor (BDNF)
BDNF is a peptide in the central nervous system (CNS) that plays a well-characterized role in synaptic plasticity, neurogenesis, neuronal survival, resilience to depression, and synaptogenesis (the formation of new synapses). However, BDNF’s unfavorable pharmacokinetics limit its therapeutic potential. Hence, exogenous administration of BDNF in human subjects suffering from neurodegenerative disease has proven disappointing. Nevertheless, because BDNF plays such an important role in promoting neuronal survival and providing trophic support for neurons, BDNF remains a promising neuronal target in neurodegenerative disease research.
Other small-molecule agonists at the BDNF receptor (Trk B), in addition to 7,8-dihydroxyflavone, include the tricyclic antidepressant Amitriptyline, and N-acetylserotonin, a precursor to the endogenous chronobiotic melatonin. Evidence suggests that Amitriptyline may have a therapeutic advantage over other antidepressants (SSRIs as well as other tricyclics), precisely because of its extra activity at the BDNF receptor. However, amitryptaline is rarely used in clinical practice due to its substantial side effect burden, especially the anticholinergic side effects.
Exercise, Depression, and BDNF
The procognitive and antidepressant effects of exercise are likely mediated by increased circulating BDNF. Moreover, the mechanism of action of almost all antidepressants, independent of class, appears to converge on enhancement of BDNF signaling to promote neurogenesis (the birth of new neurons). For example, antidepressant treatment induced BDNF mRNA expression, as well as autophosphorylation and activation of TrKB in the central nervous system (CNS). Moreover, the behavioral effects of antidepressants are reduced in mice genetically engineered to have low BDNF levels (i.e., heterozygous mice that contain only one active BDNF allele).
In addition, human subjects with the Val66Met BDNF polymorphism (where the amino acid in the 66th position in the BDNF peptide is switched from valine to methionine) may be more vulnerable to neuropsychiatric disorders. Hence, BDNF signaling likely plays a role in resilience to depression.
In summary, a defect in the BDNF peptide confers vulnerability to neuropsychiatric diseases and enhanced BDNF signaling via exercise or treatment with selective serotonin reuptake inhibitors (SSRIs) both augment BDNF levels in cerebrospinal fluid (CSF).