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haidut

haidut

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Thanks for the feedback.

All of a sudden last night I got chills... took charcoal and it went away.

But, an interesting observation, I had to go #2...

5 times throughout the night... but good bowel movements.

The soreness is better today, but still there.

I'm wondering if there is some type of infection and my body is fighting it off.

Bowel movement is expected with emodin/cascara. I think 5 is too many, so I would lower the dose.
There could be SIBO or dysbiosis in the colon that the Lapodin is helping with.
 

Owen B

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That was one of the hopes I had when conjuring it up :): The emodin in Cascara is in a glycoside form, which makes it almost unabsorbable and that's what allows it to reach the colon where bacteria break it down to plain emodin thus triggerring the laxative effect. We use pure emodin in Lapodin, which gets very well absorbed in the stomach and small intestine, with very little laxative effect.
This was the post I was searching for because my main concern with ordering Lapodin again was the experience I had with an early formulation.

Back then the laxative effect was very, very strong. It was turning me inside out.

So I don't notice any laxative effect from this version at all. But I'm worried about it's effect orally. If one of the reasons not to take it orally was the laxative effect (I know that cascara stopped working for me), and that's not a risk now, then are there any other reasons not to take it orally?

Is it absorbable? Because when I take this topically all I can think of is food.

When I take it orally it kind of has an antibiotic feel, in that it wears me down. Like some prescription antibiotics I've taken in the past that just drub me into the ground. The Lapodin is not that strong but I'm concerned that taking it orally is wasting my time.

I'm trying to clear my system of endotoxins, fungi. I've got a lot of what I think are histamine reactions and a bad skin condition I can't identify.
 

Velve921

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Bowel movement is expected with emodin/cascara. I think 5 is too many, so I would lower the dose.
There could be SIBO or dysbiosis in the colon that the Lapodin is helping with.

After 6 days the discomfort is almost completely gone. It's also been 6 days since I last took Lapodin.

I have a feeling taking it 5 days in a row was a bit too much...

I'll think more about rotating sporadically in the future
 

LeeLemonoil

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Part 4 of the NAD world: the NQ01 gene, the Warburg effect, SIRT 1 and inflammation, and possible interventions - AGINGSCIENCES™ - Anti-Aging Firewalls™

4. NQO1 regulates blood pressureby eNOS, ACE, and an LKB1/AMPK-mediated preservation in GTPCH-1

Another fascinating study showed that activation of NQO1 ameliorates spontaneous hypertension in a rat model. As you may know, spontaneous hypertension does not normally occur in rodents. But in certain strains of inbred rats, bred to develop spontaneous hypertension, high BP does occur and is thought to be mediated by a decline in nitric oxide production by endothelial cells. In this rat model of spontaneous hypertension, activation of NQO1 by beta-lapachone relieved the hypertension in these rats. The positive effects of beta-lapachone were thought to be mediated by NQO1-induction of endothelial nitric oxide (eNOS).

Another study showed that the effect of NQO1 was to regulate the acetylation of eNOS. When an eNOS inhibitor was used, the positive effects of beta-lapachone was completely blocked.

In a separate study, beta-lapachone was used to study the effects of the shedding of the enzyme angiotensin converting enzyme (ACE), which converts Angiotensin I to Angiotensin II in the blood stream. This study showed that beta-lapachone increased NQO1 activity which resulted in reduced cleavage and secretion of ACE into the extracellular space surrounding the cells that synthesized ACE.

In the most recent study, further elucidation of the eNOS mediated mechanism was analyzed and figured out. In this study, they showed that the increase in NAD+ levels in the aortic endothelial cells resulted in an increase in LKBA deacetylation, and AMPK phosphorylation. This was followed by an increase in GTP-cyclohydrolase-1 preservation and tetrahydrobiopterin/dihydrobiopterin ratio. This explained the rest of the story on how beta-lapachone reduced blood pressure.

Both beta-lapachone and the polyphenol, epicatechin, have the effect of reducing blood pressure. Beta-lapachone does this via the direct activation of NQO1, whereas epicatechin does this by activating Nrf2. Nrf2 is the transcription factor that turns on the NQO1 gene.

Summary: NQO1 elevated the ratio of NAD/NADH in the endothelial cells and increases eNOS activity via an AMPK-dependent mechanism. The increase in AMPK phosphorylation resulted in a preservation of the GTP cyclohydrolase-1 (GTPCH-1), which resulted in a lowering of blood pressure. The elevation in the NAD/NADH ratio also results in a reduced cleavage and secretion of ACE into the bloodstream, thereby reducing Angiotensin II formation. As a result of the eNOS-mediated method and the ACE-reduction mediated molecular mechanism, the hypertension in rats resolved. As a result of all this research, NQO1 activation has been recently proposed as a strategy for controlling hypertension (see lst reference below).
 

LeeLemonoil

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10. Beta-lapachone, a compound found in the bark of the South American Lapacho tree, is a potent activator of the NQO1 protein and produces ROS in cancer cells, but reduces ROS in non-cancer cells. It also inhibits pathological retinal neovascularization, but does not inhibit physiological neovascularization.

The most exciting thing about NQO1 is that there is a natural, cheap, compound found in the tree bark of a South American tree. The compound is called beta-Lapachone and is a NQO1 activator. Specifically, NQO1 is a “two-electron transfer” enzyme that can extinguish free radicals in normal cells, but produces free radicals in cancer cells. It has been shown to be a very effective compound for treating lung cancer. Here is how it works:

  • Beta-lapachone undergoes a redox cycle by NQO1, which reduces beta-lapachone to an unstable semiquinone. The semiquinone then rapidly undergoes a two-step oxidation back to the parent stable compound, beta-lapachone. This produces what is called a “perpetuating futile redox cycle”. This results in an unbalance of intracellular reactive oxygen species in cancer cells, resulting in the cell death of the cancer cells. This “perpetual futile redox cycle” is totally dependent on the concentration of NQO1 within cells. Here is a diagram of the reaction:


Illustration reference: 2014 The Chemotherapeutic Effects of Lapacho Tree Extract: β-Lapachone

The downstream effects of perpetual futile redox cycling include 4 apoptotic pathways and one necroptotic pathway:

  1. Mitochondrial-induced apoptosis – The induction of ROS in mitochondria opens the MPTP pores and results in PARP activation and caspace activation. This induces apoptosis.
  2. ER-induced apoptosis – The induction of ER stress induces sarcoplasmic release of calcium which induces high levels of cytoplasmic Ca++. This also induces apoptosis via the ER.
  3. DNA-damage mediated apoptosis – beta-lapachone also induces Topoisomerase I and II. The activation of topoisomerases induces DNA breaks, which induces PARPs. This PARP hyper-activation induces apoptosis independently from mitochondrial ROS or ER stress.
  4. Cell cycle arrest-induced apoptosis – The futile redox cycling of beta-lapachone also induces cycle cycle arrest via the activation of p21, p27, and the phosphorylation of JNK, PI3K, and Akt. This induces cancer cell apoptosis as well.
  5. Calpain-induced cell necrosis – Unlike the 4 pathways above, futile redox cycling also induces calcium influx into the cells independently of ER stress. This calcium influx into the cell activates Calpain, which induces cell death by the necrosis pathway, not the apoptosis pathway.
Conclusion: beta-lapachone induces cancer cell death by five different pathways, all dependent on perpetual futile redox cycling which is dependent on NQO1 expression. Here is a diagram that illustrates these 5 pathways:
 
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10. Beta-lapachone, a compound found in the bark of the South American Lapacho tree, is a potent activator of the NQO1 protein and produces ROS in cancer cells, but reduces ROS in non-cancer cells. It also inhibits pathological retinal neovascularization, but does not inhibit physiological neovascularization.

The most exciting thing about NQO1 is that there is a natural, cheap, compound found in the tree bark of a South American tree. The compound is called beta-Lapachone and is a NQO1 activator. Specifically, NQO1 is a “two-electron transfer” enzyme that can extinguish free radicals in normal cells, but produces free radicals in cancer cells. It has been shown to be a very effective compound for treating lung cancer. Here is how it works:

  • Beta-lapachone undergoes a redox cycle by NQO1, which reduces beta-lapachone to an unstable semiquinone. The semiquinone then rapidly undergoes a two-step oxidation back to the parent stable compound, beta-lapachone. This produces what is called a “perpetuating futile redox cycle”. This results in an unbalance of intracellular reactive oxygen species in cancer cells, resulting in the cell death of the cancer cells. This “perpetual futile redox cycle” is totally dependent on the concentration of NQO1 within cells. Here is a diagram of the reaction:


Illustration reference: 2014 The Chemotherapeutic Effects of Lapacho Tree Extract: β-Lapachone

The downstream effects of perpetual futile redox cycling include 4 apoptotic pathways and one necroptotic pathway:

  1. Mitochondrial-induced apoptosis – The induction of ROS in mitochondria opens the MPTP pores and results in PARP activation and caspace activation. This induces apoptosis.
  2. ER-induced apoptosis – The induction of ER stress induces sarcoplasmic release of calcium which induces high levels of cytoplasmic Ca++. This also induces apoptosis via the ER.
  3. DNA-damage mediated apoptosis – beta-lapachone also induces Topoisomerase I and II. The activation of topoisomerases induces DNA breaks, which induces PARPs. This PARP hyper-activation induces apoptosis independently from mitochondrial ROS or ER stress.
  4. Cell cycle arrest-induced apoptosis – The futile redox cycling of beta-lapachone also induces cycle cycle arrest via the activation of p21, p27, and the phosphorylation of JNK, PI3K, and Akt. This induces cancer cell apoptosis as well.
  5. Calpain-induced cell necrosis – Unlike the 4 pathways above, futile redox cycling also induces calcium influx into the cells independently of ER stress. This calcium influx into the cell activates Calpain, which induces cell death by the necrosis pathway, not the apoptosis pathway.
Conclusion: beta-lapachone induces cancer cell death by five different pathways, all dependent on perpetual futile redox cycling which is dependent on NQO1 expression. Here is a diagram that illustrates these 5 pathways:

Really interesting, thanks! Glad to see medical industry is finally developing interests in quinones. I hope they don't get pulled from the market...
 

Fractality

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Really interesting, thanks! Glad to see medical industry is finally developing interests in quinones. I hope they don't get pulled from the market...

Can they do that even though if it is derived from or is a natural product?
 
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haidut

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This was the post I was searching for because my main concern with ordering Lapodin again was the experience I had with an early formulation.

Back then the laxative effect was very, very strong. It was turning me inside out.

So I don't notice any laxative effect from this version at all. But I'm worried about it's effect orally. If one of the reasons not to take it orally was the laxative effect (I know that cascara stopped working for me), and that's not a risk now, then are there any other reasons not to take it orally?

Is it absorbable? Because when I take this topically all I can think of is food.

When I take it orally it kind of has an antibiotic feel, in that it wears me down. Like some prescription antibiotics I've taken in the past that just drub me into the ground. The Lapodin is not that strong but I'm concerned that taking it orally is wasting my time.

I'm trying to clear my system of endotoxins, fungi. I've got a lot of what I think are histamine reactions and a bad skin condition I can't identify.

It is getting absorbed, no matter what the route. It's already explained in the quote you included. Orally, absorbed emodin goes mostly into the liver while topically is seems to have a more systemic effect. The fact is increases hunger is probably due to its cortisol-lowering effects, which also lowers blood sugar thus triggering hunger. The AAS bodybuilders use have a similar hunger promoting effect since they block cortisol receptors.
 
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haidut

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haidut

haidut

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Obi-wan

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10. Beta-lapachone, a compound found in the bark of the South American Lapacho tree, is a potent activator of the NQO1 protein and produces ROS in cancer cells, but reduces ROS in non-cancer cells. It also inhibits pathological retinal neovascularization, but does not inhibit physiological neovascularization.

The most exciting thing about NQO1 is that there is a natural, cheap, compound found in the tree bark of a South American tree. The compound is called beta-Lapachone and is a NQO1 activator. Specifically, NQO1 is a “two-electron transfer” enzyme that can extinguish free radicals in normal cells, but produces free radicals in cancer cells. It has been shown to be a very effective compound for treating lung cancer. Here is how it works:

  • Beta-lapachone undergoes a redox cycle by NQO1, which reduces beta-lapachone to an unstable semiquinone. The semiquinone then rapidly undergoes a two-step oxidation back to the parent stable compound, beta-lapachone. This produces what is called a “perpetuating futile redox cycle”. This results in an unbalance of intracellular reactive oxygen species in cancer cells, resulting in the cell death of the cancer cells. This “perpetual futile redox cycle” is totally dependent on the concentration of NQO1 within cells. Here is a diagram of the reaction:


Illustration reference: 2014 The Chemotherapeutic Effects of Lapacho Tree Extract: β-Lapachone

The downstream effects of perpetual futile redox cycling include 4 apoptotic pathways and one necroptotic pathway:

  1. Mitochondrial-induced apoptosis – The induction of ROS in mitochondria opens the MPTP pores and results in PARP activation and caspace activation. This induces apoptosis.
  2. ER-induced apoptosis – The induction of ER stress induces sarcoplasmic release of calcium which induces high levels of cytoplasmic Ca++. This also induces apoptosis via the ER.
  3. DNA-damage mediated apoptosis – beta-lapachone also induces Topoisomerase I and II. The activation of topoisomerases induces DNA breaks, which induces PARPs. This PARP hyper-activation induces apoptosis independently from mitochondrial ROS or ER stress.
  4. Cell cycle arrest-induced apoptosis – The futile redox cycling of beta-lapachone also induces cycle cycle arrest via the activation of p21, p27, and the phosphorylation of JNK, PI3K, and Akt. This induces cancer cell apoptosis as well.
  5. Calpain-induced cell necrosis – Unlike the 4 pathways above, futile redox cycling also induces calcium influx into the cells independently of ER stress. This calcium influx into the cell activates Calpain, which induces cell death by the necrosis pathway, not the apoptosis pathway.
Conclusion: beta-lapachone induces cancer cell death by five different pathways, all dependent on perpetual futile redox cycling which is dependent on NQO1 expression. Here is a diagram that illustrates these 5 pathways:

This is excellent info @LeeLemonoil. The tea has 1500mg's per serving which I am now sipping throughout the day. Lapodin only has 5 mgs per serving
 

LeeLemonoil

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@Obi-wan

thanks, I recommend reading the entire series of the "NAD-world by James WAtson, where the bit is taken from. It's enlightening stuff in every respect, not only cancer.
 

Lee Simeon

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This is excellent info @LeeLemonoil. The tea has 1500mg's per serving which I am now sipping throughout the day. Lapodin only has 5 mgs per serving
Wait is there 1500 mg Beta Lapachone for each cup of paud arco tea? Have been trying to find a number on it for some time, but I have not found anything. This is way more than I expected!
 

LeeLemonoil

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I know, but you made it sound as if the tea contained 1500mg of beta-lapachone whole it’s rally 1500mg of Paz D’Arco -bark that contains unknown amounts of it
 

Obi-wan

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