All things Histone Deacetylase (HDAC) and DNA Methyl Transferase (DNMT) inhibitory - reversing epigenetics from metabolic insults
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@CrumblingCookie said in All things Histone Deacetylase (HDAC) and DNA Methyl Transferase (DNMT) inhibitory - reversing epigenetics from metabolic insults:
Thank you for sharing. I learned a lot
Here is why he maybe didn't warm up to SCFAs like butyrate, as he connected their synthesis to the many drawbacks associated with the abundance of gastrointestinal bacterial fermentation [...]
Yeah, this explains my negative experiences with butyrate a long time ago...
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@Kvirion said:
Yeah, this explains my negative experiences with butyrate a long time ago...
What do you remember about them?
I don't see how exogenous butyrate supplementation fits into Peat's objections as this foregoes the whole endogenous synthesis from bacterial fermentation. The But is not the cause for fermentation with all its associated endotoxin production but an isolated result of it. -
I've started taking 100mg apigenin twice daily.
However, the half-life of apigenin in rodents is reportedly much longer (several days) than in humans (a few hours) so I'm as yet uncertain about the ultimate dosage.Apigenin, luteolin and chrysin are all congeneric,
with apigenin having 2 hydroxygroups at its B-ring,
luteolin having only one OH-group at its B-ring and
chrysin having none and being the weakest HDACi of those.• They inhibit HDAC as well as DNMT and also Histone Methyltransferase (HMT), which is distinct from Histone Demethylase LSD1.
• The mechanism for DNMTi is different than the one by EGCG.
• Their DNMTi ist similarly powerful as 5-Aza-dC! Which sounds impressive because Aza is super toxic and irreversebly damaging to DNA.
• They also inhibit in particular the trimethylation of H3K2 through inhibition of EZH2 (Enhancer of zeste homolog 2).-
In our study, DNMT inhibition by plant flavones seems to be due to the binding of flavones at the catalytic binding pocket of DNMTs. These might be different from catechol-containing polyphenols, such as epigallocatechic-3-gallate, in which the noncompetitive inhibition of DNA methylation catalyzed by DNMTs is majorly due to the higher levels of SAM resulting from the catechol-O-methyltransferase-mediated O-methylation of these compounds
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Our results showed that the intercalation of flavones with calf thymus DNA causes major reductions in the intensity of the UV-Vis absorption band characteristics between 260–280 nm, where Apigenin and Luteolin with the 1 and 2 hydroxy groups in the B ring resulted in significant intercalation with DNA. Chrysin (no hydroxyl group in the B ring) resulted in less significant DNA binding.
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Because Apigenin and Luteolin are less water soluble than Chrysin, they are less solvated and consequently susceptible to intercalation within DNA.
Dietary Flavones as Dual Inhibitors of DNA Methyltransferases and Histone Methyltransferases
Overall, apigenin sounds very promising and powerful.
Whilst also being an aromatase inhibitor one one hand the caveat is that it's really exerting estrogenic and progestogenic effects on the other hand. Which seem quite unpredictable. -
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@CrumblingCookie said in All things Histone Deacetylase (HDAC) and DNA Methyl Transferase (DNMT) inhibitory - reversing epigenetics from metabolic insults:
What do you remember about them?
It was before peating. I had IBS-D, and butyrate increased my fluctuance and GI discomfort and probably forced me to visit the toilet more often...
Regarding apigenin, I'm interested in your experiences.
BTW, what do you think about some MAO-A inhibition by apigenin?
https://link.springer.com/article/10.1007/BF02977772
