21 replies to this topic

[Phoebus]

Am reading up on the flavonoid called myricetin and discovered it easily the most potent natural inhibitor of PARP-1, by far. 

 

This paper compare different flavonoids ability to inhibit PARP-1, based on percentages 

 

https://academic.oup...10/2190/4664443

 

Fisetin - 60%

 

Quercetin - 62% 

 

Naringenen - 21%

 

About 15 others rated at 0% - 20% 

 

Myricetin - 93% inhibition of PARP-1! 

 

PARP is a consumer of NAD+ on the one hand and lowering PARP levels will raise NAD+ levels. However I do wonder if lowering PARP too much is a good thing since PARP plays a role in DNA repair. Or maybe these flavonoids actually have DNA protecting qualities and therefore lower PARP indirectly by preventing DNA damage and therefore making PARP activation unnecessary? 

 

Anyway if you are looking for a great food based source of both Myricetin and quercetin I found that Moringa has both in very high amounts 

 

https://www.scienced...308814607012137

 

This study shows various foods like carrots and apples , cauliflower have myricetin levels between 200 - 1,000 mg/kg. Meanwhile moringa clocks in at 5,800 mg/kg! 

 

It also has the most quercetin of any veggie/fruit tested at 281 mg/kg, more than double the amount apples have. Quercetin of course is both a senolytic, and a CD38 suppressor. So I think Moringa is a fantastic addition to any anti aging stack. 

 

 

[Phoebus]

Now to answer my question as to whether or not Myr or Quer protect the DNA, here it is 

 

https://www.scienced...383571897001071

 

 

 

The effects of the flavonoids quercetin and myricetin, and the antihepatotoxic agent silymarin, on hydrogen peroxide-mediated DNA damage in human lymphocytes were determined using alkaline single-cell gel electrophoresis (the comet assay). Treatment with hydrogen peroxide increased the levels of DNA strand breaks and oxidised pyrimidine bases in these cells. Quercetin was protective at concentrations above 10 μM and myricetin decreased oxidant-induced DNA strand breakage at concentrations of 100 μM. Cellular metabolism may alter the antioxidant efficacy of the flavonoids. Silymarin had no protective effect at any of the concentrations tested. None of these flavonoids was itself genotoxic. Neither α-tocopherol nor β-carotene decreased hydrogen peroxide-induced DNA breakage. The differences in effectiveness of these dietary compounds against oxidative DNA damage may be explained by differences in their chemical structure or location within the cell.

 

Both flavonoids protected the DNA against oxidative damage from H2O2. Meanwhile milk thistle, vit E, and beta carotene did nothing in this experiment. 

 

This is evidence that Myr may not be directly inhibiting PARP-1, but rather it has DNA protecting qualities and therefore when Myr is present there is little need to activate PARP since part of its job it to do DNA repair. 

 

And here is another study showing myr, quer, and rutin all protect DNA from damage by H2O2 while also showing them to be entirely non-toxic to healthy cells 

 

https://pubmed.ncbi....h.gov/10578483/

Edited by Phoebus, 07 April 2021 - 09:12 PM.

[pamojja]

Interesting. Moringa isn't mentioned in http://phenol-explor...fter-hydrolysis

Walnuts seem to have a lot too: Walnut 65.21 mg/100 g FW

Quercetin seems highest in: Black elderberry 42.00 mg/100 g FW

http://phenol-explor...#chromatography

Edited by pamojja, 07 April 2021 - 10:01 PM.

[Michael]

Flavonoid myricetin is the most potent natural PARP-1 inhibitor, which boosts NAD+ levels

"... in Pulmonary Epithelial Cells." We're a decade on; no one has shown that this happens in vivo, and the structure of these flavonoids has not even been tweaked into a patentable drug, despite PARP inhibitors being a lucrative and widely-pursued drug category.

[Phoebus]

The study I linked showed Quer. content 

 

apples - 120 mg/kg 

 

apricot - 322 

 

moringa - 281 

 

So I misspoke before, moringa is not the highest, apricot is. But moringa is still twice what apples are and has a crazy high level of myr. I am assuming the quer and myr survive the processing of moringa leaves into powder and I will be ordering some moringa powder based on my research 

[Phoebus]

"... in Pulmonary Epithelial Cells." We're a decade on; no one has shown that this happens in vivo, and the structure of these flavonoids has not even been tweaked into a patentable drug, despite PARP inhibitors being a lucrative and widely-pursued drug category.

 

These researchers say it has been proven in vivo 

 

https://www.hindawi....cl/2015/894597/

 

 

 

Previously we have established that dietary flavonoids inhibit PARP both in vitro and in vivo [17–19]. Flavonoids are polyphenolic compounds which are found in fruits, vegetables, and plant-derived products like red wine and tea [18]. Flavonoids have been shown to display positive health effects, for example, reduced risks for cardiovascular and chronic inflammatory diseases [20–23], which have been ascribed to their antioxidant and anti-inflammatory properties [22, 24]. We now studied the effect on NAD+ levels in endothelial cells after exposing the cells to high glucose in the presence or absence of flavonoids. In addition we determined whether three structurally related flavonoids are also able to inhibit aldose reductase, the most important enzyme of the polyol pathway

 

 

1. L. Geraets, H. J. J. Moonen, K. Brauers et al., “Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression,” European Journal of Pharmacology, vol. 573, no. 1–3, pp. 241–248, 2007.View at: Publisher Site | Google Scholar
2. L. Geraets, H. J. J. Moonen, K. Brauers, E. F. M. Wouters, A. Bast, and G. J. Hageman, “Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose) polymerase-1 in pulmonary epithelial cells,” Journal of Nutrition, vol. 137, no. 10, pp. 2190–2195, 2007.View at: Google Scholar
3. A. R. Weseler, L. Geraets, H. J. J. Moonen et al., “Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes,” Journal of Nutrition, vol. 139, no. 5, pp. 952–957, 2009.View at: Publisher Site | Google Scholar

[Michael]

 

These researchers say it has been proven in vivo 

 

https://www.hindawi....cl/2015/894597/

 

 

For this "fact," they cite their references (17-19). All of these studies are of cells in vitro — including (18), which is the same pulmonary epithelial cell study with which you led.

[Hip]

In order to translate these in vitro results to their in vivo effects, you would need to do some pharmacokinetic calculations, to work out the blood levels of these supplements obtained with a given oral dose. 

 

Two important factors affect the final blood levels obtained: oral bioavailability and plasma protein binding. If the former is low and the latter is high, this can greatly reduce the blood concentration of the free supplement.

 

Thus the most effective supplement in vivo may not necessarily be the one with the most potent effect in vitro. 

[Kentavr]

PARP-1 helps repair cells.

At an older age, an increase in PARP-1 occurs due to the fact that cells require increased repair.

If you directly inhibit PARP-1, you will only make your body worse.

 

PARP-1 should go down by itself. For example, due to increased levels of glutathione. If you increase your glutathione levels, your cells need less repair, and therefore PARP-1 activity will decrease.

[Turnbuckle]

PARP is a consumer of NAD+ on the one hand and lowering PARP levels will raise NAD+ levels. 

 

 

​It's very easy to raise NAD+ levels with nicotinamide + ribose.

[Phoebus]

 

PARP-1 helps repair cells.

At an older age, an increase in PARP-1 occurs due to the fact that cells require increased repair.

If you directly inhibit PARP-1, you will only make your body worse.

 

PARP-1 should go down by itself. For example, due to increased levels of glutathione. If you increase your glutathione levels, your cells need less repair, and therefore PARP-1 activity will decrease.

 

 

In the study I linked above myricetin  protected the DNA against oxidative damage from H2O2. Therefore it may be suppressing PARP indirectly due to the fact that less DNA repair is needed and therefore less PARP is produced. 

[Kentavr]

Due to the above facts, the inclusion of mericetin in the GEROPROTECT Ageless Cell product from the Life Extention company looks very strange.

 

https://www.lifeexte...ct-ageless-cell

 

The PARP-1 level decreases, the cell becomes "Ageless" and in fact is not repaired. The cell lives longer, the body gets worse, the consumption of other supplements increases, everyone is happy? 

[Kentavr]

In the study I linked above myricetin  protected the DNA against oxidative damage from H2O2. Therefore it may be suppressing PARP indirectly due to the fact that less DNA repair is needed and therefore less PARP is produced. 

 

 

Оxidative damage from H2O2 -  this damage is due to ROS (reactive oxygen species). Glutathione protects against this.

 

Now, attention, a question!

 

You have injected myricerin and INCREASED ROS. And the PARP-1 level dropped by 93%. Do you think this is good or bad? 

[Phoebus]

why would consuming a flavonoid increase ROS? I don't understand. 

[Kentavr]

why would consuming a flavonoid increase ROS? I don't understand. 

 

H2O2 simulates an increase in oxygen radicals.

 

1. You have injected myricerin  ---- 2. INCREASED ROS with H2O2 --- 3. PARP-1 (reduced 93%) = >  cells with many damages. But more NAD + 

 

Can we assume that such a result can be obtained? A decrease in PARP-1 does not mean cell protection.

 

 

But even if we assume that the protection works, perhaps 91% is too much a decrease and may not be appropriate.

For the sake of protection, you will be forced to eat myricetin, and after 5 years, so much damage will accumulate in your cells that you will need to do forced apoptosis.

Edited by Kentavr, 18 May 2021 - 02:59 PM.

[Phoebus]

First off no one is "injecting" myricetin, or any other flavonoid, to my knowledge 

 

Secondly why would consuming a flavonoid increase H2O2? 

 

Do you have a study or something that shows this? 

[Kentavr]

First off no one is "injecting" myricetin, or any other flavonoid, to my knowledge 

 

Secondly why would consuming a flavonoid increase H2O2? 

 

Do you have a study or something that shows this? 

 

I use google translate and it translates a little bit wrong. I mean oral intake of myricetin.

 

Example:

 

1. You took myricetin by mouth.

2. Then you have increased the level of free radicals through the introduction of hydrogen peroxide.

3. Your PARP-1 level (for example) dropped by 91% and does not rise higher. But this does not mean that the cage does not need repair.

 

If your PARP-1 level has not increased, it may be bad.

 

A decrease in PARP-1 does not mean cell protection.

 

P.S.: A forced reduction in PARP-1 can be very bad in the long run. Our cells must be repaired. I would keep the PARP-1 level below 50% - 60%.

Edited by Kentavr, 18 May 2021 - 03:31 PM.

[Phoebus]

 

2. Then you have increased the level of free radicals through the introduction of hydrogen peroxide.

 

 

I keep asking you the same question over and over again 

 

WHY do you think consuming flavonoids increases free radicals and/or H2O2? 

 

what proof or evidence do you have of this? 

 

thanks 

[Kentavr]

I keep asking you the same question over and over again 

 

WHY do you think consuming flavonoids increases free radicals and/or H2O2? 

 

what proof or evidence do you have of this? 

 

thanks 

 

Flavonoids DO NOT increase free radicals. They intercept them.

 

In order to test how well free radicals are trapped, flavonoids are introduced.

 

One of the most common free radicals is the superoxide anion radical. It is formed in mitochondria when they do not work properly.

 

To simulate the formation of reactive oxygen species, hydrogen peroxide is used. Hydrogen peroxide easily forms various forms of active oxygen in the body (an approximate imitation is obtained).

[Kentavr]

If the PARP-1 level drops by 93% even with the intake of myricetin, when there are many reactive oxygen species in the body, this may mean that myricetin itself inhibits PARP-1. Because it is unlikely that PARP-1 will fall so much in such stressful conditions.

 

Hence, it follows that PARP-1 in the presence of myricetin does not work in the body even with a large amount of free radicals. This is bad.

 

As I understand it.

Edited by Kentavr, 18 May 2021 - 04:03 PM.

[Kentavr]

 

If the PARP-1 level drops by 91% even with the intake of myricetin, when there are many reactive oxygen species in the body, this may mean that myricetin itself inhibits PARP-1. Because it is unlikely that PARP-1 will fall so much in such stressful conditions.

 

Hence, it follows that PARP-1 in the presence of myricetin does not work in the body even with a large amount of free radicals. This is bad.

 

As I understand it.

 

 

It could also mean that supplements containing myricetin can harm the body in the long term. A person may feel better, but cells will accumulate damage by inhibiting PARP-1.

 

As a result, cells can age and fail faster because they are poorly repaired.

 

But there will be a false feeling that you are full of strength. However, at one point everything can deteriorate sharply. Years at 60. And it will be very difficult to fix, if not impossible. This could be a trap.

 

 

Edited by Kentavr, 18 May 2021 - 03:54 PM.

[Groundhog Day]

 

If the PARP-1 level drops by 93% even with the intake of myricetin, when there are many reactive oxygen species in the body, this may mean that myricetin itself inhibits PARP-1. Because it is unlikely that PARP-1 will fall so much in such stressful conditions.

 

Hence, it follows that PARP-1 in the presence of myricetin does not work in the body even with a large amount of free radicals. This is bad.

 

As I understand it.

 

 

 

In cancer, PARP1 is upregulated and plays a role in shaping progression of the cancer, specifically related to inflammatory signaling, angiogenesis, and metastasis. 

 

So inhibiting it is a target for a variety of cancers, most notably the BRACA 1/2 ones.