Flavonoids belong to a family of polyphenolic compounds, which are widely found in
a variety of fruits, vegetables, tea and wine. More importantly, flavonoids are served as
one type of the active ingredients in traditional Chinese medicines. Different lines of
evidence support that flavonoids have impacts in many aspects of human health,
including anti-tumor, anti-oxidation and anti-inflammation. Recently, numerous attentions have been focused on the neuronal beneficial effects of flavonoids, including the
neuroprotection against neurotoxin stress, as well as the promotion of memory, learning
and cognitive functions. Previous studies in cultured cortical neurons and PC12 cells
showed that flavonoids possessed the abilities of anti-oxidation and inhibiting the
Aβ-induced cytotoxi...[
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Flavonoids belong to a family of polyphenolic compounds, which are widely found in
a variety of fruits, vegetables, tea and wine. More importantly, flavonoids are served as
one type of the active ingredients in traditional Chinese medicines. Different lines of
evidence support that flavonoids have impacts in many aspects of human health,
including anti-tumor, anti-oxidation and anti-inflammation. Recently, numerous attentions have been focused on the neuronal beneficial effects of flavonoids, including the
neuroprotection against neurotoxin stress, as well as the promotion of memory, learning
and cognitive functions. Previous studies in cultured cortical neurons and PC12 cells
showed that flavonoids possessed the abilities of anti-oxidation and inhibiting the
Aβ-induced cytotoxicity. These properties made the flavonoids to be the potential
candidates for drug development for Alzheimer’s disease. In this study, the bioactivities
of flavonoids were screened and determined in nervous system. Specifically, the
induction of neurite outgrowth, the modulation of synapse formation, and the promotion
on the synthesis and secretion of neurotrophic factors were further revealed in neuron
and astrocyte.
After screening of 65 flavonoids, 20 flavonoids were found to up regulate the protein
levels of neurofilaments, which are the main protein markers for neurite outgrowth.
Amongst the 20 flavonoids, sulphureting, luteolin, daidzin, genistein, genistin, hyperin
and isorhamnetin could increase the protein levels of neurofilaments for over 3 folds. The
flavonol aglycone, isorhamnetin, was found to have the most promising effect in up
regulating the expression of neurofilaments. In addition to this neuronal differentiation
effect, the application of isorhamnetin in cultured PC12 cells could potentiate the effect of
nerve growth factor (NGF) in promoting neurite outgrowth. For mechanistic delineation, it
was found that isorhamnetin alone could not activate the NGF-induced signaling pathway, and which could not potentiate the effect of NGF in activating the downstream
signaling molecules. For the modulation of synapse formation, the flavonoids,
(-)-catechin, luteolin and isorhamnetin, were found to stimulate the expressions of
synaptic proteins including synaptotagmin, synapsin II, synaptosomal-associated protein
25 and post-synaptic density protein 95 in cultured cortical and hippocampal neurons.
But none of these flavonoids could stimulate the release of neurotransmitters including
glutamate and γ-aminobutyric acid. For the regulation of neurotrophic factors, calycosin,
isorhamnetin, luteolin and genistein, were found to be highly effective in inducing the
synthesis and secretion of the neurotrophic factors, i.e. NGF, glial cell-derived
neurotrophic factor and brain-derived neurotrophic factor. For the molecular mechanism,
it was demonstrated that the flavonoid-induced signaling responses were similar to that
of estrogen receptor-dependent signaling pathway.
Here, different flavonoids were found to possess neuronal beneficial effects in
different aspects. Some flavonoids, including isorhamnetin, luteolin and genistein, were
found to be effective in the studies of neurite outgrowth, synaptogenesis, and
neurotrophic factor expressions, as described above. This supported the multi-functional
properties of flavonoids. In clinical studies, flavonoids have been used for promoting
memory and cognition functions in aging and neurological disorders. Indeed, the present
study fully explained these phenomena both in cellular and molecular levels. More importantly, these flavonoids might be considered as the good candidates in developing
potential drugs, or health food supplements, in treating, or preventing different
neurological disorders.
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