Jump to content
The Corroboree
Alchemica

Flavonoids as dopaminergic neuromodulators

Recommended Posts

Flavonoids as dopaminergic neuromodulators

The present study aimed to characterize and evaluate flavonoids effects on organic cation uptake in neuronal cells. Uptake experiments were conducted using radiolabeled methyl-4-phenylpyridinuim ([(3) H]-MPP(+) ), in human neuronal dopaminergic cells, SH-SY5Y. Catechin did not alter [(3) H]-MPP(+) uptake, however its metabolite 4'-methyl-catechin decreased it by almost 50%. Epicatechin and its methylated metabolites also decreased [(3) H]-MPP(+) uptake. Interestingly, the quercetin flavonol and its metabolite conjugated with glucuronic acid, as well as the flavanones naringenin and hesperitin, increased [(3) H]-MPP(+) uptake. These results showed that different classes of flavonoids, as well as its metabolites, differently influence neuronal organic cation uptake. Several xeno- and endobiotics, including neurotransmitters, are organic cations. Specific food recommendations may be beneficial in pathological conditions where levels of neurotransmitters, as dopamine, are either increased or decreased.

The full text may be interesting?

  • Like 3

Share this post


Link to post
Share on other sites

Thanks to members of this community :wub:

  • after ingestion, flavonoids are subjected to metabolism which consequently has an impact on biological activity
  • Although permeability of blood-brain barrier to flavonoids has been demonstrated, the range of concentrations that could be in contact with neurons is still not clear

"The effect of different flavonoids and some of their metabolites on organic cation uptake in dopaminergic neurons was tested. Catechin did not induce significant alterations on [3H]-MPP+ uptake; however its metabolite 4’-methyl-catechin decreased it. Epicatechin was able to decrease [3H]-MPP+ uptake only at the higher concentration tested (100 μM). Curiously, a lower concentration of the 3’-methyl-epicatechin and 4’-methyl-epicatechin, two of its metabolites, had the same effect, significantly decreasing [3H]-MPP+ uptake."

[The] "...methylated forms of this compounds, one the most abundant forms circulating in vivo, showed a consistent inhibition of [3H]-MPP+ uptake that should be biologically relevant."

"Quercetin, one of the most widespread flavonoid in the human diet, at the higher concentration tested, increased [3H]-MPP+ uptake and 3-quercetin glucuronide, one of the main quercetin metabolite, also increased [3H]-MPP+ uptake at 30 μM.

Naringenin and hesperitin, two representative flavanones, increased [3H]-MPP+ uptake but this effect was not concentration dependent."

post-5043-0-76975100-1448784306_thumb.jp

This work results’ showed a partial involvement of DAT on [3H]-MPP+ uptake, and therefore, a possible involvement of flavonoids on modulation of this transporter. DAT is responsible for the removal of dopamine from the synaptic cleft. Inhibition of this uptake by flavan-3-ols can affect neurotransmission by increasing dopamine on the level of the synaptic cleft. However naringenin, hesperitin, quercetin and metabolites increased this uptake. This increase can be helpful in psychoses where levels of dopamine are increased on synaptic cleft as schizophrenia or situations of drugs abuse like methamphetamines and cocaine.

Overall, this work showed that organic cations uptake in dopaminergic neurons may be modulated by diet flavonoids and most interesting, by its biological metabolites, in structural-dependent way. This uptake seems to be regulated by Ca2+ pathways, phosphorylation/dephosphorylation mechanisms and have a partial involvement of DAT. These results suggested a possible interference of flavonoids with neurotransmitters transport, namely dopamine reuptake which may be relevant to explain the potential neuroprotective actions of some flavonoids.

A well-balanced diet, rich in vegetables and fruits where chocolate, tea and grapes are good sources of catechin and epicatechin, citrus fruit have abundant amounts of flavonones and onions and apples are rich sources of quercetin, may be helpful in restoring homeostasis in different dopamine disorders. Thus, despite the care that should be taken in extrapolating in vitro results, this study suggested that flavan-3-ols rich food could be helpful in Parkinson’s Disease while flavonols and flavonones sources could be more useful in people with psychoses or drug addiction.

See also:

Flavonoids and the CNS

GABAA modulation

Protective Mechanisms of Flavonoids in Parkinson's Disease.

Edited by Alchemica
  • Like 3

Share this post


Link to post
Share on other sites

The full text may be interesting?

When is it ever not? Even when I don't understand half of it right now it's usually fun later on. So many ramifications

  • Like 1

Share this post


Link to post
Share on other sites

My foundations are shaky in many areas :wink: We all help put the pieces together

From Turnera diffusa, flavonoids such as apigenin [wiki] and others have been isolated [1] [2].



Edited by Alchemica
  • Like 1

Share this post


Link to post
Share on other sites

Apigenin is close to naringenin/hesperitin (dihydroapigenin is naringenin) so, by their hypothesis, it could be suspected at increasing organic cation (drug) uptake.

The quercetin bit interested me, I wonder if this is why I tend to have an inexplicable craving for apples after consuming anorexigenic dopamine analogs. Like my neurons saying 'yes, please' :wink:

  • Like 2

Share this post


Link to post
Share on other sites

The quercetin bit interested me, I wonder if this is why I tend to have an inexplicable craving for apples after consuming anorexigenic dopamine analogs. Like my neurons saying 'yes, please' :wink:

Mmm, Is it found in some types of pear as well? They're related species. I totally used to get pear cravings after anorexigenic dopamine analogues benders back in the day. I assumed it was a gut thing of some kind, but maybe quercetin is neuroprotective?

No use me googling the chem, it'd just confuse me :D Words of one syllable or less please.

Share this post


Link to post
Share on other sites

Some pears contain ~28mg/kg quercetin according to this

maybe quercetin is neuroprotective?

Flavonoids as a class are considered neuroprotective [1] They may also demonstrate prooxidant effects which could be therapeutically relevant in some cases [2, 3]

Quercetin may have hypnotic activity, possibly mediated by the serotonergic system [4]

Edited by Alchemica
  • Like 1

Share this post


Link to post
Share on other sites

Some pears contain ~28mg/kg quercetin according to this

Love your work, thank you. It was always Buerre Bosc pears too, not sure if that was cos they were the only type which would survive the trip home over gravel roads on the bike, or whether it was pure instinct :)

Flavonoids as a class are considered neuroprotective [1] They may also demonstrate prooxidant effects which could be therapeutically relevant in some cases

Damn, of course they are, that being the point of your original post. Sry, am really scattered today, broken sleep cycle for a few days because I've had to reschedule work around avoiding having stuff plugged in while lightning and storms are round. I'm cancelling all my rocket surgery appointments.

Geez I've gotten soft in me old age

Edited by Darklight
  • Like 1

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now

×