11 replies to this topic

[Flex]

I wanted to make a little summary of compounds that I´ve found and I will add some further ones by time.

Be aware that HDAC or epigenetic alteration isnt allways good.

I believe to read ( but really not sure) somewhere that a inhibition of a certain HDAC is actually increasing the chance for dementia or something like that.

So try not to handle this that easily, but with caution.

E.g. find allways first something that can reverse the effects before using something

and try to get as much as possible informed.

Here´s no Doctor who advises You !

 

The first study really catched my eyes, but I dont know whether they can act in the CNS.

Note the effects of e.g. Ginger on Table 2.

It opposes actually some actions of HDAC inhibitors, but those particular upregulations could be good for cocaine addiction.

 

Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells

Zyflamend down-regulated the expression of all class I and II histone deacetylases where Chinese goldthread and baikal skullcap (two of its components) appear to be primarily responsible for these results.

http://www.biomedcen...1472-6882/14/68

http://www.biomedcen.../14/68/table/T2

 

miRNA are relative new discoveries that have a great influence on Epigenetics.

Cocaine exerts neuronal adaptions partly via miRNA modulation

Example:

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

http://www.plosone.o...al.pone.0052701

Via miR-133b cocaine would modulate the expression of pitx3 and subsequently of dopamine receptors, dat and th. These results indicate that miRNAs can play an important role during embryogenesis and in drug addiction.

 

Curcumin has also some influence on miRNA:

 

..Recently, Sun et al. (2008) reported that curcumin altered miRNA expression in human pancreatic cancer cells. After 72 h of incubation, 11 miRNAs were significantly up-regulated and 18 were down-regulated by curcumin. Among these, miRNA-22 was the most significantly up-regulated and miRNA-199a* the most down-regulated.

Effect of curcumin on miRNA expression...

 

perhaps on Methylation too:

 

Only a few reports have so far investigated the effect of curcumin on DNA methylation. Molecular docking of the interaction between curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of DNMT1 to exert its inhibitory effect on DNA methylation (Liu et al. 2009). However, a more recent study showed no curcumin-dependent demethylation, which suggested that curcumin has little or no pharmacologically relevant activity as a DNMT inhibitor (Medina-Franco et al. 2010). To clarify these contradictions, more research is urgently needed.

Epigenetic changes induced by curcumin and other natural compounds

http://www.ncbi.nlm....les/PMC3092901/

http://www.ncbi.nlm....port=objectonly

 

VS

 

Curcumin as a regulator of epigenetic events

http://www.google.de....80185997,d.ZWU

 

Nicotinamide wich is supposedly a SIRT 1&2 inhibitor

Mechanistic studies on the effects of nicotinamide on megakaryocytic polyploidization and the roles of NAD+ levels and SIRT inhibition.

http://www.ncbi.nlm....pubmed/19715739

 

This hydrolysis yields O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, itself an inhibitor of sirtuin activity.

http://www.biovision...etric-5706.html

Edited by Flex, 20 November 2014 - 08:02 PM.

[Muad'Dib]

I found this

Table 1

Common HDAC, HAT and DNMT modulators derived from natural sources

Natural inhibitor References HDAC    Allyl mercaptan Nian et al. (2008)  Amamistatin Fennell and Miller (2007)  Apicidin Darkin-Rattray et al. (1996)  Azumamide E Maulucci et al. (2007)  Caffeic acid Waldecker et al. (2008)  Chlamydocin Brosch et al. (1995)  Chlorogenic acid Bora-Tatar et al. (2009)  Cinnamic acid Bora-Tatar et al. (2009)  Coumaric/hydroxycinnamic acid Waldecker et al. (2008)  Curcumin Bora-Tatar et al. (2009)  Depudecin Kwon et al. (1998)  Diallyl disulfide Lea et al. (1999)  Equol Hong et al. (2004)  Flavone Bontempo et al. (2007)  Genistein Kikuno et al. (2008)  Histacin Haggarty et al. (2003)  Isothiocyanates Ma et al. (2006)  Largazole Ying et al. (2008)  Pomiferin Son et al. (2007)  Psammaplin Pina et al. (2003)  SAHA (Vorinostat) Richon et al. (1998)  S-allylmercaptocysteine Lea et al. (2002)  Sulforaphane Myzak et al. (2004)  Trapoxin (Kijima et al. 1993)  Ursolic acid Chen et al. (2009)  Zerumbone Chung et al. (2008) HAT  Allspice Lee et al. (2007)  Anarcardic acid Balasubramanyam et al. (2003), Ghizzoni et al. (2010)  EGCG Choi et al. (2009a)  Curcumin Balasubramanyam et al. (2004), Marcu et al. (2006)  Gallic acid Choi et al. (2009b)  Garcinol Balasubramanyam et al. (2004)  Quercetin Ruiz et al. (2007)  Sanguinarine Selvi et al. (2009)  Plumbagin Ravindra et al. (2009) DNMT  Genistein Day et al. (2002)  EGCG Fang et al. (2003)  Psammaplins Pina et al. (2003)  Quercetin, fisetin, myricetin Lee et al. (2005)  Caffeic acid Lee and Zhu (2006)  Chlorogenic acid Lee and Zhu (2006)  Curcumin Moiseeva et al. (2007)  Parthenolide Liu et al. (2009)  Mahanine Sheikh et al. (2010)

SAHA Suberoylanilide hydroxamic acid, EGCG epigallocatechin gallate

 

[Flex]

Cool thanks !

Will look into this

[Flex]

Found this one and it seems to be a Goldmine.

Theres the text

Epigenetics in Traditional Chinese Pharmacy: A Bioinformatic Study at Pharmacopoeia Scale

http://www.hindawi.c...011/816714/sup/

 

and here is the table of the compounds:

downloads.hindawi.com/journals/ecam/2011/816714.f1.pdf

 

It mentions also herbs that alter MBD(Methyl-CpG-binding domain), PcG and Dicer

 

Btw. by inhibiting Dnmt1, (Dnmt3 are just methylating, whereas Dnmt1 is sustaining the methylation state) the gene become demethylated. So afaik in the most cases activated.

This isnt allways good when You consider that mao-a can also be activated and therefore a drop of 5-ht DA and NE as well as oxidative damage can occur.

On the other hand, Herbs that have an ihibitory action on Dnmt1 afaik dont seem to have any bad effects. A secondary mechanism from the plans could prevent this.

( But as usual, no guarantees from me)

 

I didnt read everything but if some data is based on cell cultures (in vitro) instead of animals (in vivo), then it could´nt be allways accurate, since in the body are several factors that "could" prevent this action.

Nevertheless: enjoy the table

Edited by Flex, 08 December 2014 - 06:54 PM.

[Flex]

Thymoquinone (TQ)  from Nigella sativa is also a HDAC inhibitor (at least in Vitro):

 

A review on therapeutic potential of Nigella sativa: A miracle herb

..TQ also increased p21 WAF1 expression, inhibited HDAC activity, and induced histone hyperacetylation. HDAC inhibitors have been shown to ameliorate inflammation-associated cancer...

http://www.ncbi.nlm....les/PMC3642442/

[Flex]

Not sure whether this repeats the informations of post #4 but anyway:

 

Targeting Neurogenesis: A Promising Therapeutic Strategy for Post-Stroke Treatment with Chinese Herbal Medicine

http://www.karger.co...icle/PDF/362638

 

[Flex]

Not sure whether this one cis the same like from post #1, but anyway:

Histone modifications and traditional Chinese medicinals

http://www.biomedcen...472-6882/13/115

 

It was found that 1,170 or 36% of the 3,294 TCM medicinals interact with human histone-modifying enzymes. Among the histone-modifying medicinals, 56% of them promote chromatin condensation. The cold-hot natures of TCM medicinals were found to be phylogenetically correlated. Furthermore, cold (hot) TCM medicinals were found to be associated with heterochromatinization (euchromatinization) through mainly H3K9 methylation and H3K4 demethylation. The associations were weak yet statistically significant. On the other hand, analysis of TCM formulas, the major form of TCM prescriptions in clinical practice, found that 99% of 200 government approved TCM formulas are histone-modifying. Furthermore, in formula formation, heterochromatic medicinals were found to team up with other heterochromatic medicinals to enhance the heterochromatinization of the formula. The synergy was mainly through concurrent DNMT and HDAC inhibition, co-inhibition of histone acetylation and H3S10 phosphorylation, or co-inhibition of H3K4 demethylation and H3K36 demethylation.

 

government = certain herbs that are classified traditionally as such.

Other classifications are e.g. minister, which are thought to have a supportive role.

 

More informations are in the hindawi articel in post #4 or #1

[gamesguru]

Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage

Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins

 

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

EGCG was reported to inhibit enzymes involved in DNA methylation, and was subsequently identified as a histone modifier [192-194]. EGCG inhibited HDAC activity and increased histone acetylation in prostate [192], skin [193], and breast cancer cells [194]. Pandey et al. [192] demonstrated that EGCG reduced mRNA expression of HDAC1, HDAC2, and HDAC3, leading to re-expression of GSTP1 in prostate cancer cells ... Interestingly, Choi et al. [195] identified EGCG as a HAT inhibitor that suppressed transcription factor p65 (RelA) acetylation, thereby inhibiting nuclear factor kappa B (NFκB), interleukin 6 (IL6), and downstream target genes. In addition to the HAT and HDAC activities, EGCG inhibited polycomb group (PcG) proteins [196] that are key epigenetic regulators [197]. Treatment of skin cancer cells with EGCG reduced expression of PcG proteins BMI-1 and EZH2, leading to global reduction of histone H3K27me3 and reduced cell survival

 

Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1

Butyrate (NaB), one of the principal products of dietary fiber fermentation, induces differentiation of colon cancer cell lines by inhibiting histone deacetylases (HDACs). On the other hand, (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG), two abundant phenolic compounds of green tea, have been shown to exhibit antitumoral properties. In this study we used colon cancer cell lines to study the cellular and molecular events that take place during co-treatment with NaB, EC and EGCG. We found that (i) polyphenols EC and EGCG fail to induce differentiation of colon adenocarcinoma cell lines; (ii) polyphenols EC and EGCG reduce NaB-induced differentiation; (iii) the effect of the polyphenols is specific for NaB, since differentiation induced by other agents, such as trichostatin A (TSA), was unaltered upon EC and EGCG treatment, and (iv) is independent of the HDAC inhibitory activity of NaB

 

Though tea will also inhibit HAC:

Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor

During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase

EGCG prevents TNFα-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-κB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-κB target genes in response to diverse stimuli

EGCG reduced the binding of p300 to the promoter region of interleukin-6 gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-κB–mediated inflammatory signaling pathway. Importantly, EGCG at 50 μmol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases.

Edited by gamesguru, 13 August 2015 - 04:11 PM.

[Flex]

forgott to mention that rehmannia glutinosa inhibits dnmt1

 

though, its written in the Hindawi link

[Area-1255]

Flex, you always find the most interestingly intricate compilations buddy!

[Flex]

Thanks Youre found many interresting and essential things ;-)

Edited by Flex, 14 September 2015 - 07:50 PM.