1084 replies to this topic

[health_nutty]

I beat Sirtris' SRT-501 taking a tagamet.

That is a pretty bold claim with absolutely zero evidence to back it up.

[krillin]

Suppose I could temp shut off your stomach's ability to digest with an H2 antagonist?

The RES would be able to pass into your small intestine and raise your plasma levels before your liver conjugates it.

I beat Sirtris' SRT-501 taking a tagamet.

Friends don't let friends drink and post.

[bixbyte]

Suppose I could temp shut off your stomach's ability to digest with an H2 antagonist?

The RES would be able to pass into your small intestine and raise your plasma levels before your liver conjugates it.

I beat Sirtris' SRT-501 taking a tagamet.

Friends don't let friends drink and post.

Thanks Krillin, my designated driver.

[edward]

I understand what you were trying to say bixbyte.

We could go one step further....

All get J-Tube ports http://www.oncolink..../phit/jtube.gif

http://www.infantref...oto.php/photo/5

Ports for direct tube feeding into the jejunum of the small intestine, then we could give Sirtris a run for their money.... Ahh might as well just find an injectable form, daily IM injections are just what we need.

Edited by edward, 13 February 2008 - 08:19 PM.

[bixbyte]

I understand what you were trying to say bixbyte.

We could go one step further....

How about an omental flap closure?
Using a Radical surgery procedure to Maximize RES effects?
I could bypass my stomach right into the small int

http://www.springerl...dyjx21nb7qbwh0/

Get lots of RES that way!

Or something less EXTREME

An OTC dose of Cimetine on an empty stomach about 1/2 hour before the RES?
I am just trying to temp shut off some of the stomach's H2 and allow the RES to make it to the small intestine.
The side effects of Cimetine are well documented.

[maxwatt]

I understand what you were trying to say bixbyte.

We could go one step further....

How about an omental flap closure?
Using a Radical surgery procedure to Maximize RES effects?
I could bypass my stomach right into the small int

http://www.springerl...dyjx21nb7qbwh0/

Get lots of RES that way!

Or something less EXTREME

An OTC dose of Cimetine on an empty stomach about 1/2 hour before the RES?
I am just trying to temp shut off some of the stomach's H2 and allow the RES to make it to the small intestine.
The side effects of Cimetine are well documented.

I tried it with PepcidAC, another H2 inhibitor. Half an hour before 2 grams of resveratrol with ethanol and Miralax. I noticed no difference.
Of course I can drink three cups of coffee before bed and sleep like a baby, which indicates my CYP1A et al is hyperactive, so partially shutting down H2 for me might not have much effect. One thing shutting down H2 is supposed to do is reduce flushing when drinking, and lots of Asians carry around Pepcid AC for this purpose. It also slows getting intoxicated. But I wouldn't know, I tried that too and couldn't tell any difference.

[niner]

An OTC dose of Cimetine on an empty stomach about 1/2 hour before the RES?
I am just trying to temp shut off some of the stomach's H2 and allow the RES to make it to the small intestine.
The side effects of Cimetine are well documented.

But Bix, resveratrol's not affected by stomach acid. Blocking H2 receptors really shouldn't have any effect on resveratrol absorption.

[bixbyte]

I understand what you were trying to say bixbyte.

We could go one step further....

How about an omental flap closure?
Using a Radical surgery procedure to Maximize RES effects?
I could bypass my stomach right into the small int

http://www.springerl...dyjx21nb7qbwh0/

Get lots of RES that way!

Or something less EXTREME

An OTC dose of Cimetine on an empty stomach about 1/2 hour before the RES?
I am just trying to temp shut off some of the stomach's H2 and allow the RES to make it to the small intestine.
The side effects of Cimetine are well documented.

I tried it with PepcidAC, another H2 inhibitor. Half an hour before 2 grams of resveratrol with ethanol and Miralax. I noticed no difference.
Of course I can drink three cups of coffee before bed and sleep like a baby, which indicates my CYP1A et al is hyperactive, so partially shutting down H2 for me might not have much effect. One thing shutting down H2 is supposed to do is reduce flushing when drinking, and lots of Asians carry around Pepcid AC for this purpose. It also slows getting intoxicated. But I wouldn't know, I tried that too and couldn't tell any difference.

Empty stomach?

You Forgot to drink a full glass of grapefruit juice.

(Wipe that frown off ur face)

[bixbyte]

An OTC dose of Cimetine on an empty stomach about 1/2 hour before the RES?
I am just trying to temp shut off some of the stomach's H2 and allow the RES to make it to the small intestine.
The side effects of Cimetine are well documented.

But Bix, resveratrol's not affected by stomach acid. Blocking H2 receptors really shouldn't have any effect on resveratrol absorption.

I am trying to get by my old liver before digestion.
Without inserting a jjtube like in ur previous post.

[Smith]

Hello,
I'm new here, but I've read through some of the posts about mixing RESV with DMSO. Back in 2004-2005 (when Prohormones were still legal), the two ideal ways of getting the pro-hormones into your system were either transdermal via a carrier or as a methylated capsule. The methylation would prevent the liver from breaking down the prohormone before it got into the bloodstream, hence M1T (methylated 1-Testosterone) was very popular. I tried both methods, and both were very effective, the sub-dermal sprays would come pre-measured in a spray bottle, with 2-3 sprays on the inner thighs and chest area (where the skin is the thinnest) would deliver the proper dosage of the prohormone.

Assuming one ordered the 70/30 DMSO spray bottle (thru the link posted earlier) of 237 mL and also assuming that only 50% of the RESV will make it into the bloodstream, one could figure out how much RESV to mix into the spray bottle to determine how much resv would get into your bloodstream per spray. Using the 237 mL DMSO bottle, I determined it took 18 sprays to generate 2.5mL of liquid, that means each spray pumps out 0.139 mL of DMSO (70/30). .. (anyone care to double check this?)

So, I calculated that if you mixed in 14.7 g of RESV into the 237 mL spray bottle, each spray will give you 8.61mg of RESV, and assuming a 50% absorption rate & 5L of blood, that gives 3.77uM blood concentration per spray. A study posted earlier in the thread concluded that 5uM in vitro was needed to get anti-cancerious effects, whereas a 5g oral dose only gave somewhere between 2-3uM (if I remember correctly). So with this concentration, two sprays should give around 7uM blood concentration of RESV. And the bottle would last a whopping 1706.4 sprays, or 853 applications!! The only thing I'm not sure about is the absorption rate... I'm just guessing at 50%, it could be higher.

I think it would be easier to just dump 14.7g of RESV in the bottle and use it from there. The bottle is non-transparent, so light shouldn't degrade the RESV. Anyone care to comment on this?

Edited by Smith, 21 February 2008 - 05:23 AM.

[niner]

and assuming a 50% absorption rate [...] The only thing I'm not sure about is the absorption rate... I'm just guessing at 50%, it could be higher.

Sadly, it could be lower. Way lower. It basically is not possible, even with DMSO, or some other permeation enhancer, to get enough resveratrol into general circulation to do any good. Resveratrol is absorbed pretty well orally. The reason that its bioavailability is so poor is because it is very efficiently sulfated and glucuronidated in the liver and gut. That's why you need large quantities of it.

With testosterone, you were probably trying to get microgram amounts in, while with resveratrol, in order to deal with the conjugations above, you would need thousands of times as much.

[Smith]

and assuming a 50% absorption rate [...] The only thing I'm not sure about is the absorption rate... I'm just guessing at 50%, it could be higher.

Sadly, it could be lower. Way lower. It basically is not possible, even with DMSO, or some other permeation enhancer, to get enough resveratrol into general circulation to do any good. Resveratrol is absorbed pretty well orally. The reason that its bioavailability is so poor is because it is very efficiently sulfated and glucuronidated in the liver and gut. That's why you need large quantities of it.

With testosterone, you were probably trying to get microgram amounts in, while with resveratrol, in order to deal with the conjugations above, you would need thousands of times as much.

malbecman in Post #99 stated that he dissolved 100mg of RESV w/DMSO on his arm, and only a little powder was left, indicating that most of the 100mg was trasferred transdermally via the carrier DMSO. I chose a 50% absorption because of RESV's tendancy to get absorbed into fatty tissues. Why do you think less than 50% of the RESV absorbed dermally gets into the bloodstream? I can perhaps see that the rate of absorption dermally could be slower than orally, thus giving the liver more time to sulfate the RESV thus reducing peak RESV count in the bloodstream, but do you have any evidence to that effect? On the contrary, there seems to be anecdotal evidence of the effectiveness of RESV and DMSO in the prior postings on this thread.. If the RESV is not getting into the bloodstream, where is the 100mg of RESV going and how much would you estimate gets into the bloodstream?

Edited by Smith, 21 February 2008 - 06:20 AM.

[Smith]

Wanted to add one more thought...

RESV appears to be a good candidate for transdermal delivery. First, it's highly soluble in DMSO (someone posted 400mg/ml), and its got a low molecular weight of 228.28. There was a post in the DMSO thread about how molecules with molecular weights of < 500 tend to be good candidates for transdermal delivery.

A small Nicoderm CQ patch is able to deliver 21mg of nicotine per day. It seems reasonable that a wide spray of DMSO solution onto a large surface area such as the inner thighs should be able to deliver 8.61mg of RESV in a much shorter time period, as I calculated in my earlier post. Comments?

Edited by Smith, 21 February 2008 - 06:48 AM.

[niner]

and assuming a 50% absorption rate [...] The only thing I'm not sure about is the absorption rate... I'm just guessing at 50%, it could be higher.

Sadly, it could be lower. Way lower. It basically is not possible, even with DMSO, or some other permeation enhancer, to get enough resveratrol into general circulation to do any good. Resveratrol is absorbed pretty well orally. The reason that its bioavailability is so poor is because it is very efficiently sulfated and glucuronidated in the liver and gut. That's why you need large quantities of it.

With testosterone, you were probably trying to get microgram amounts in, while with resveratrol, in order to deal with the conjugations above, you would need thousands of times as much.

malbecman in Post #99 stated that he dissolved 100mg of RESV w/DMSO on his arm, and only a little powder was left, indicating that most of the 100mg was trasferred transdermally via the carrier DMSO. I chose a 50% absorption because of RESV's tendancy to get absorbed into fatty tissues. Why do you think less than 50% of the RESV absorbed dermally gets into the bloodstream? I can perhaps see that the rate of absorption dermally could be slower than orally, thus giving the liver more time to sulfate the RESV thus reducing peak RESV count in the bloodstream, but do you have any evidence to that effect? On the contrary, there seems to be anecdotal evidence of the effectiveness of RESV and DMSO in the prior postings on this thread.. If the RESV is not getting into the bloodstream, where is the 100mg of RESV going and how much would you estimate gets into the bloodstream?

Check out this post: http://www.imminst.o...&...st&p=222129
In it I talk about how much methyl salicylate you can get through skin. Resveratrol, due to its structure, is far far less permeant than methyl salicylate. Once it's through the skin, it tends to hang out in the subdermal fat and muscle, and not get into general circulation. I didn't have the PK data at the time, but the next post after that one presented the data and the amount in general circulation is truly minuscule. Many people make the mistake of forgetting about metabolism, also. The vast majority of whatever resveratrol does get into circulation will be quickly metabolized into one of the conjugate forms, thus mostly taken out of consideration.

The nicotine patch may be a red herring, as the mean lethal dose of nicotine in adults is 30-60 mg. Not all the nicotine in the patch gets in, and what does get in occurs over many hours, so there are many hours worth of metabolism removing it at the same time.

[Smith]

Check out this post: http://www.imminst.o...&...st&p=222129
In it I talk about how much methyl salicylate you can get through skin. Resveratrol, due to its structure, is far far less permeant than methyl salicylate. Once it's through the skin, it tends to hang out in the subdermal fat and muscle, and not get into general circulation. I didn't have the PK data at the time, but the next post after that one presented the data and the amount in general circulation is truly minuscule. Many people make the mistake of forgetting about metabolism, also. The vast majority of whatever resveratrol does get into circulation will be quickly metabolized into one of the conjugate forms, thus mostly taken out of consideration.

The nicotine patch may be a red herring, as the mean lethal dose of nicotine in adults is 30-60 mg. Not all the nicotine in the patch gets in, and what does get in occurs over many hours, so there are many hours worth of metabolism removing it at the same time.

Thanks for the info. Based the article you quoted in your post, and the MW of Reservatrol, the Log Jmax (Max Flux) of RESV is about -8.23, I havent calculated how much surface area would be needed to get 8-16mg absorbed in an hour... Also, there is an interesting study on transdermal RESV here.

[Smith]

Perhaps I'm just hoping that transdermal RESV will work, because its so much cheaper than taking RESV orally... Anyway, The study referenced earlier by Niner is great, as it allows us to predict the amount of a chemical that penetrates the skin based solely upon its molecular weight...

Transdermal RESV:

MW of RESV: 228.24
Predicted Flux: 10^-8.237 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 0.36
RESV in blood/hour (assuming 5L and only 50% makes it): 0.16 uM

* doesn't look very good, as an oral 5g dose gives around 2.5 uM

But, now lets look at RESV dissolved in DMSO:

MW of DMSO: 78.13
Predicted Flux: 10^-5.384 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 257.88
RESV in blood/hour (assuming 5L and only 50% makes it): 113.13 uM!!


What do you guys think?? I'm not sure that one can ignore the MW of RESV just cause its dissolved in DMSO, but with DMSO as the carrier, it may make sense, as it is fully dissolved in the DMSO carrier.

Edited by Smith, 21 February 2008 - 10:19 PM.

[Hedgehog]

Perhaps I'm just hoping that transdermal RESV will work, because its so much cheaper than taking RESV orally... Anyway, The study referenced earlier by Niner is great, as it allows us to predict the amount of a chemical that penetrates the skin based solely upon its molecular weight...

Transdermal RESV:

MW of RESV: 228.24
Predicted Flux: 10^-8.237 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 0.36
RESV in blood/hour (assuming 5L and only 50% makes it): 0.16 uM

* doesn't look very good, as an oral 5g dose gives around 2.5 uM

But, now lets look at RESV dissolved in DMSO:

MW of DMSO: 78.13
Predicted Flux: 10^-5.384 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 257.88
RESV in blood/hour (assuming 5L and only 50% makes it): 113.13 uM!!


What do you guys think?? I'm not sure that one can ignore the MW of RESV just cause its dissolved in DMSO, but with DMSO as the carrier, it may make sense, as it is fully dissolved in the DMSO carrier.

In Rats
IP dosing

w/ DMSO @ 200mg/kg (Resveratrol dissolved in DMSO (100 mM resveratrol))
Cmax of 17uM
Tmax of 0.1
AUC of 25
T1/2 of 0.44

[Hedgehog]

Perhaps I'm just hoping that transdermal RESV will work, because its so much cheaper than taking RESV orally... Anyway, The study referenced earlier by Niner is great, as it allows us to predict the amount of a chemical that penetrates the skin based solely upon its molecular weight...

Transdermal RESV:

MW of RESV: 228.24
Predicted Flux: 10^-8.237 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 0.36
RESV in blood/hour (assuming 5L and only 50% makes it): 0.16 uM

* doesn't look very good, as an oral 5g dose gives around 2.5 uM

But, now lets look at RESV dissolved in DMSO:

MW of DMSO: 78.13
Predicted Flux: 10^-5.384 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 257.88
RESV in blood/hour (assuming 5L and only 50% makes it): 113.13 uM!!


What do you guys think?? I'm not sure that one can ignore the MW of RESV just cause its dissolved in DMSO, but with DMSO as the carrier, it may make sense, as it is fully dissolved in the DMSO carrier.

In Rats
IP dosing

w/ DMSO @ 200mg/kg (Resveratrol dissolved in DMSO (100 mM resveratrol))
Cmax of 17uM
Tmax of 0.1
AUC of 25
T1/2 of 0.44

There are a lot of different ways of formulating this drug.

Quick release to get a high Cmax, slow release and have a longer T1/2.

It really depends on what you want to achieve? If you want a quick fast Cmax then take Biotiva, if you want a long lasting effect take Revgenetics.

[Smith]

In Rats
IP dosing

w/ DMSO @ 200mg/kg (Resveratrol dissolved in DMSO (100 mM resveratrol))
Cmax of 17uM
Tmax of 0.1
AUC of 25
T1/2 of 0.44

Exactly where did you get your information? Do you have a reference to a published study? That would be interesting to see.

200mg/kg w/DMSO? Unless I'm mistaken, that is alot of RESV to be absorbed transdermally.

Edited by Smith, 22 February 2008 - 01:51 AM.

[niner]

Perhaps I'm just hoping that transdermal RESV will work, because its so much cheaper than taking RESV orally... Anyway, The study referenced earlier by Niner is great, as it allows us to predict the amount of a chemical that penetrates the skin based solely upon its molecular weight...

Transdermal RESV:

MW of RESV: 228.24
Predicted Flux: 10^-8.237 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 0.36
RESV in blood/hour (assuming 5L and only 50% makes it): 0.16 uM

* doesn't look very good, as an oral 5g dose gives around 2.5 uM

But, now lets look at RESV dissolved in DMSO:

MW of DMSO: 78.13
Predicted Flux: 10^-5.384 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 257.88
RESV in blood/hour (assuming 5L and only 50% makes it): 113.13 uM!!

What do you guys think?? I'm not sure that one can ignore the MW of RESV just cause its dissolved in DMSO, but with DMSO as the carrier, it may make sense, as it is fully dissolved in the DMSO carrier.

I don't think that you can use the MW of the DMSO. The paper I referenced above was not that great. Their model for transdermal absorption really performed pretty badly. By just using MW, you could be off by orders of magnitude. The main value of the paper was the large dataset contained in the supplemental materials.

You are still ignoring metabolism here. You have to consider that something like 95% of the resveratrol that gets in is going to be sulfated or glucuronidated. Also, 50% making it into systemic circulation is way too high.

[niner]

In Rats
IP dosing

w/ DMSO @ 200mg/kg (Resveratrol dissolved in DMSO (100 mM resveratrol))
Cmax of 17uM
Tmax of 0.1
AUC of 25
T1/2 of 0.44

Exactly where did you get your information? Do you have a reference to a published study? That would be interesting to see.

200mg/kg w/DMSO? Unless I'm mistaken, that is alot of RESV to be absorbed transdermally.

It's not transdermal. In this case they are injecting the DMSO/RESV solution into the peritoneal cavity. IP stands for intraperitoneal.

[Smith]

Perhaps I'm just hoping that transdermal RESV will work, because its so much cheaper than taking RESV orally... Anyway, The study referenced earlier by Niner is great, as it allows us to predict the amount of a chemical that penetrates the skin based solely upon its molecular weight...

Transdermal RESV:

MW of RESV: 228.24
Predicted Flux: 10^-8.237 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 0.36
RESV in blood/hour (assuming 5L and only 50% makes it): 0.16 uM

* doesn't look very good, as an oral 5g dose gives around 2.5 uM

But, now lets look at RESV dissolved in DMSO:

MW of DMSO: 78.13
Predicted Flux: 10^-5.384 mole/cm^2/hr
Application Area: 200cm^2
mg/hour: 257.88
RESV in blood/hour (assuming 5L and only 50% makes it): 113.13 uM!!

What do you guys think?? I'm not sure that one can ignore the MW of RESV just cause its dissolved in DMSO, but with DMSO as the carrier, it may make sense, as it is fully dissolved in the DMSO carrier.

I don't think that you can use the MW of the DMSO. The paper I referenced above was not that great. Their model for transdermal absorption really performed pretty badly. By just using MW, you could be off by orders of magnitude. The main value of the paper was the large dataset contained in the supplemental materials.

You are still ignoring metabolism here. You have to consider that something like 95% of the resveratrol that gets in is going to be sulfated or glucuronidated. Also, 50% making it into systemic circulation is way too high.

Assuming the algorithm presented in the paper for predicting skin flux based on MW is not too far off and that we can use the DMSO MW... then even if only 10% of the resveratrol gets into systemic circulation (instead of 50%), you are still left with a blood concentration of 3.62uM.. Still signifcantly higher than a 5g oral dose... I know, thats alot of assumptions, but are you sure that transdermal RESV via DMSO as carrier has no merit?

Edited by Smith, 22 February 2008 - 11:41 PM.

[Hedgehog]

In Rats
IP dosing

w/ DMSO @ 200mg/kg (Resveratrol dissolved in DMSO (100 mM resveratrol))
Cmax of 17uM
Tmax of 0.1
AUC of 25
T1/2 of 0.44

Exactly where did you get your information? Do you have a reference to a published study? That would be interesting to see.

200mg/kg w/DMSO? Unless I'm mistaken, that is alot of RESV to be absorbed transdermally.

It's not transdermal. In this case they are injecting the DMSO/RESV solution into the peritoneal cavity. IP stands for intraperitoneal.

I guess my point was that this would be your max res concentration if ALL resveratrol got absorbed into the plasma with dmso+skin.

[niner]

Assuming the algorithm presented in the paper for predicting skin flux based on MW is not too far off and that we can use the DMSO MW... then even if only 10% of the resveratrol gets into systemic circulation (instead of 50%), you are still left with a blood concentration of 3.62uM.. Still signifcantly higher than a 5g oral dose... I know, thats alot of assumptions, but are you sure that transdermal RESV via DMSO as carrier has no merit?

The algorithm is pretty horrible, really. It would be better to look up the flux coefficient for chemically similar compounds. But even if the algorithm is getting it right in this case, I really don't think you can use the assumed flux of DMSO and apply it to resveratrol. The rate of flux is going to be a lot closer to the first one that you calculated, even if the DMSO does help a little. If you use that flux and a more reasonable 10% getting through, which I think 10% might still be on the high side, and you allow for 95% conjugation, then you get 0.0016 uM, at least theoretically. Transdermal delivery doesn't deliver the drug quickly, but rather over the course of hours. All the while, the liver is happily eating it up, churning out the more water-soluble conjugates that are then excreted, so your final concentrations are even lower by a good bit than what you've calculated.

Edited by niner, 23 February 2008 - 01:03 AM.

[krillin]

Maybe there is a drawback to green tea. It induces UGT1A8 and UGT1A10, the latter being able to glucuronidate resveratrol. The second paper's full text shows that mice given 5, 10, and 20 mg/kg had dose-dependent induction. Dividing by 12.3 to get a human equivalent, those are modest doses.

To confuse things, PMID: 11950788 found that EGCG inhibited glucuronidation by UGT1A1, which also hits resveratrol. EGCG also inhibited sulfation, with the paper implying that SULT1A1 (which hits resveratrol) was predominant.

Zhonghua Yi Xue Za Zhi. 2006 Jan 10;86(2):82-7.
[The role of NF-E2-related factor 2 in the induction of uridine 5'-diphosphate-glucuronosyltransferase 1A and its isoforms by epigallocatechin gallate in colon cancer cells]
[Article in Chinese]
Yang XY, Zhao WP, Li YQ, Sun ZY, Zhang Y, Guo YT, Yuan JH, Zhu Q, Wang M.
Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China.

OBJECTIVE: To investigate the role of human transcription factor NF-E2-related factor 2 (Nrf2) in the induction of the gene expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A and its isoforms by epigallocatechin gallate (EGCG). METHODS: (1) Human colon carcinoma cells Caco-2 and HT-29 were cultured. Immunocytochemistry, western blotting and confocal laser microscopy were used to detect the protein expression of Nrf2. Twenty samples of colon carcinoma with surrounding normal tissues were collected during endoscopic course. (2) RNA interference expression vector pSilencer 3.1-H1 was used to construct four Nrf2-trageting plasmids: pSilence-Nrf2-A, B, C, and D and a control pSilence-CON. Cells were transfected with pSilence-Nrf2 for 48 hours to observe the effects of transient transfection. Cells were stably transfected with pSilence-Nrf2-B for 4 weeks and re-named as Caco-2-siNrf2 and HT-29-siNrf2 (siNrf2 cells), and others stably transfected with blank plasmid pSilencer 3.1-H1 were used as controls. (3) EGCG was added into the culture fluid of cells before and after the stably transfection. RT-PCR was used to detect the mRNA expression of Nrf2, UGT1A, UGT1A8 and UGT1A10 in cells and the samples of human colon cancer tissue. RESULTS: (1) The expressions of UGT1A8 and UGT1A10 mRNA were significantly lower than that in the surrounding healthy mucosa. (2) The mRNA expression of Nrf2, UGT1A8, and UGT1A10 increased by 1.8-9.2 times after the addition of EGCG (all P < 0.05). Immunocytochemistry, western blotting and immunofluorescence demonstrated a significant increase of Nrf2 protein expression in the nucleus after treatment with EGCG. (3) SalIenzyme digestion and DNA sequencing confirmed that pSilence-Nrf2-A, B, C, and D and pSilence-CON were all successfully constructed. The inhibition rate of Nrf2 gene expression was above 80% 48 h after transfection with pSilence-Nrf2-B, and that was no significant difference after transfection with pSilence-CON (P > 0.05). There was specific inhibition of Nrf2 in Caco-2-siNrf2, HT-29-siNrf2 cells (both P < 0.01). (4) The basal levels of UGT1A8 and UGT1A10 mRNA expression in the Caco-2-siNrf2 and HT-29-siNrf2 cells were lower by 15%-65% in comparison with those in control, and the induction of genes by EGCG was largely attenuated in them (all P > 0.05). CONCLUSION: Nrf2 is localized in the cytoplasm of non-stimulated cells, and EGCG triggered its rapid nuclear accumulation. Suppression of Nrf2 gene expression results in down-regulation of the constructive expression of UGT genes and their induction by EGCG. EGCG induces the expression of UGT1A, UGT1A8 and UGT1A10 genes via a Nrf2-dependent mechanism.

PMID: 16620709

Pharmacology. 2007;80(4):269-78. Epub 2007 Jul 26.
Inhibition of epigallocatechin gallate on orthotopic colon cancer by upregulating the Nrf2-UGT1A signal pathway in nude mice.
Yuan JH, Li YQ, Yang XY.
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, PR China.

Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has many anti-carcinogenic activities. The aim of the present study was to investigate whether EGCG could prevent the occurrence or metastases of orthotopic colon cancer and probe the underlined mechanisms. We observed the inhibition of EGCG on growth and metastases of colon tumor implanted orthotopically in the cecum of nude mice. Immunohistochemistry and Western-blotting analysis were used to detect NF-E2-related factor 2 (Nrf2) protein expressions. RT-PCR was also applied to detect the mRNA levels of Nrf2, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A, UGT1A8 and UGT1A10 in colon tumors. As a result, the inhibition rates on tumor growth in the 3 EGCG groups were significantly different (all p < 0.001) compared with the control group. In addition, different doses of EGCG were able to inhibit liver and pulmonary metastases to varying degrees. The protein level of Nrf2 and the mRNA levels of Nrf2, UGT1A, UGT1A8 and UGT1A10 significantly increased in EGCG-treated mice in comparison with the control group (all p < 0.01). The results demonstrated that EGCG has a preventive effect on the growth and liver and pulmonary metastases of orthotopic colon cancer in nude mice, and this anticancer effect could be partly caused by activating the Nrf2-UGT1A signal pathway. © 2007 S. Karger AG, Basel.

PMID: 17657175

[Francis Siefken]

As an alternative to the oral route the transdermal and sublingual ways have been explored.
I hear nothing about the possibilities regarding nasal insufflation or anal administration. Would these have benefits over the other routes?

[maxwatt]

As an alternative to the oral route the transdermal and sublingual ways have been explored.
I hear nothing about the possibilities regarding nasal insufflation or anal administration. Would these have benefits over the other routes?

Don't forget Vaginal.

The short answer is "no", you cannot absorb enough resveratrol through these routes to raise serum levels sufficiently.

Edited by maxwatt, 15 March 2008 - 05:46 PM.

[inawe]

Don't forget Vagina.

The short answer is "no", you cannot absorb enugh through these routes to raise serum levels sufficiently.

No? I read somewhere that it raised the serum levels of Kristen in
$4,300.

[maxwatt]

Don't forget Vagina.

The short answer is "no", you cannot absorb enugh through these routes to raise serum levels sufficiently.

No? I read somewhere that it raised the serum levels of Kristen in
$4,300.

I don't understand what you are saying.

[inawe]

Don't forget Vagina.

The short answer is "no", you cannot absorb enugh through these routes to raise serum levels sufficiently.

No? I read somewhere that it raised the serum levels of Kristen in
$4,300.

I don't understand what you are saying.

Forget it. It was intended as a joke. I saw the word vagina and couldn't control myself. I have to learn how to take vaginas more seriously.