5 replies to this topic

[Hedgehog]

Hi All,

it appears all talk of Polydatin has stopped since I was here last. (maybe for good reason)

Just to catch you all up. Trans-Polydatin is a form of resveratrol that is much more water soluble and found in much larger concentrations in wine (search pubmed and you can see that it is impressive and varies a lot from different wines while resveratrol stays more constant in different types of wines). As you probably know resveratrol goes through phases of metabolism. Anyways, it appears that this site is still trying to get around this first pass metabolism of resveratrol including oral delivery. Maybe a pro-drug is still a good approach?

It has been known for many articles and even recent articles that Polydatin gets converted to resveratrol during the first pass metabolism. Here is the most recent

This indicates that in the rats, trans-polydatin is absorbed in a dose-dependent manner and undergoes extensive first-pass deglycosylation and glucuronidation. Orally administered trans-polydatin, therefore, is metabolized primarily to resveratrol in the small intestine and liver, where it is further metabolized to the glucuronidated resveratrol.
http://www.ncbi.nlm....mp;ordinalpos=6

Edited by Hedgehog, 29 December 2009 - 06:20 AM.

[niner]

Just to catch you all up. Trans-Polydatin is a form of resveratrol that is much more water soluble and found in much larger concentrations in wine (search pubmed and you can see that it is impressive and varies a lot from different wines while resveratrol stays more constant in different types of wines). As you probably know resveratrol goes through phases of metabolism. Anyways, it appears that this site is still trying to get around this first pass metabolism of resveratrol including oral delivery. Maybe a pro-drug is still a good approach?

It has been known for many articles and even recent articles that Polydatin gets converted to resveratrol during the first pass metabolism. Here is the most recent

This indicates that in the rats, trans-polydatin is absorbed in a dose-dependent manner and undergoes extensive first-pass deglycosylation and glucuronidation. Orally administered trans-polydatin, therefore, is metabolized primarily to resveratrol in the small intestine and liver , where it is further metabolized to the glucuronidated resveratrol.

Hi D, nice to see you back. Polydatin is interesting, but does it get you around the glucuronidation/sulfation problem? It sounds from this paper that it doesn't, although with the higher solubility maybe it swamps the gut and/or liver? That's just a speculation. Resveratrol doesn't suffer from poor absorption as it is, although polydatin would probably be better still, but it seems like they would both have the same problem with phase II metabolism. Has anyone ever done a pharmacokinetic study on polydatin, following the resveratrol product?

[Hedgehog]

Hi Niner,

Thanks its been a while... I'm still biking and just recently picked up swimming! swam 3.6km the other day for the first time... I was stupid and decided to get on a bike and go up some cat2 hills after words...

I have read a number of articles on this. The article above dosed various amounts and achieved pretty good Cmax resveratrol concentration... Also don't forget a few hrs after you take resveratrol it probably goes through enterohepatic recirculation

• 50mg/kg of polydatin --> 393 ng/mL resveratrol
• 100mg/kg of polydatin --> 858 ng/mL resveratrol
• 300mg/kg of polydatin --> 1147 ng/mL resveratrol

Niner plz help with this one....

Normal resveratrol route when taking by powder:
resveratrol-->intestinal cells (resveratrol + metabolites)-->blood--->resveratrol goes to different cells-->Liver (resveratrol gets broken down into more metabolites)

Normal polydatin route when taking by powder:
polydatin-->intestinal cells (resveratrol + fewer metabolites)-->blood---> more resveratrol goes to different cells-->Liver (resveratrol gets broken down into more metabolites)


here is a snippet of the article... (this is one of the better articles that I have read in a LONG time)... Very well done.. Had lots of supporting documents and got similar results to other papers...

This is pretty dense and took me a couple of times to b4 I understood


When trans-polydatin was orally administered to the rats (300 mg kg−1), the ratio of exposures (AUC0−t) of trans-polydatin to the total drug (trans-polydatin + metabolites) detected in the plasma is 1.6%; the ratio of glucuronidated trans-polydatin to the total drug determined in plasma is 10.7%; the ratio of resveratrol to total drug detected in plasma is 3.7%; the ratio of glucuronidated resveratrol to total drug detected in plasma is 84%. These results indicate that the proportion of trans-polydatin in plasma was very small and that considerable amounts of resveratrol are formed after oral administration of trans-polydatin. Previous work demonstrated that when trans-polydatin was orally administered to rats at a dose of 240 mg kg−1, considerable amounts of resveratrol were detected in the contents of the intestine and cecum (22). The results of in situ perfusion of the rat small intestine and liver also indicate that the hydrolysis of trans-polydatin by β-glucosidases and the glucuronidation of trans-polydatin and resveratrol by UDP-glucuronosyltransferases can occur in the intestine and the liver, thus allowing the quantity of trans-resveratrol available from the diet to be greater. The in vivo bioactivity of trans-polydatin may partially result from its metabolite (resveratrol). Previous study shows that there are two possible pathways by which trans-polydatin is hydrolyzed in the intestine. The first is a cleavage by the cytosolic-β-glucosidase (CBG), after passing the brush-border membrane by SGLT1 (sodium dependent glucose transport 1). The second is deglycosylation on the luminal side of the epithelium by the membrane-bound enzyme lactase phlorizin hydrolase (LPH), followed by passive diffusion of the released aglycone, which is further metabolized inside the cells into two glucuronides (23). Recent studies have shown that the transport of resveratrol-glucuronide conjugate and resveratrol-sulfate conjugate is mediated by multidrug resistance protein 3 (MRP3, ABCC3) and/or breast cancer resistance protein (BCRP, ABCG2), which are located in the basolateral and apical membranes of enterocytes, respectively. The absence of Mrp3 in mice results in altered disposition of resveratrol-3-glucuronide and its parent compound resveratrol, leading to a reduced percentage of resveratrol being excreted via the urine in Mrp3(−/−) mice (24).

To our knowledge, this is the first study assessing the dose-dependent absorption and first-pass metabolism of trans-polydatin in vivo. The results indicate trans-polydatin can be absorbed in a dose-dependent manner and undergoes extensive first-pass deglycosylation and glucuronidation in rats. The main glucuronide conjugate in rat is resveratrol-glucuronide after oral administration of trans-polydatin. High levels of resveratrol are formed after oral administration of trans-polydatin, increasing the quantity of trans-resveratrol available from the diet.

Although many studies have implicated a role of resveratrol in disease prevention, its role in human health as a dietary non-nutritional bioactive compound is controversial. This is because of its low abundance in the diet and its low bioavailability. To understand the beneficial effects of consuming resveratrol or polydatin on humans, some essential questions remain to be answered: (1) What are the optimal dosages of resveratrol or polydatin that should be consumed to induce a health benefit? (2) Is long-term supplementation with high doses of resveratrol or polydatin safe?


Here are some other supporting papers...

Transport, deglycosylation, and metabolism of trans-piceid by small intestinal epithelial cells.
CONCLUSIONS: This study demonstrates that the transepithelial transport of trans-piceid occurs at a high rate and that the compound is deglycosylated in trans-resveratrol. There are two possible pathways by which trans-piceid is hydrolyzed in the intestine. The first is a cleavage by the CBG, after passing the brush-border membrane by SGLT1. The second is deglycosylation on the luminal side of the epithelium by the membrane-bound enzyme LPH, followed by passive diffusion of the released aglycone, which is further metabolized inside the cells into two glucuronoconjugates.

HPLC determination of polydatin in rat biological matrices: Application to pharmacokinetic studies

Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells.
Determination of piceid in rat plasma and tissues by high-performance liquid chromatographic method with UV detection

http://www.jstage.js...56/11/1592/_pdf

comments are welcome! =)

[Hedgehog]

I wish I had taken part in this research because the article echoes a lot of things that I have been thinking about...

Although there is considerable evidence that transresveratrol
possesses strong biological activity, wine has a low
level of trans-resveratrol in comparison to its glucoside transpolydatin
(piceid, trans-3,5,40-trihydroxylstilbene-3-mono-D-glycoside).
In fact, the level of trans-polydatin in red wine is 10 times
greater than the level of trans-resveratrol (4 ). Therefore, transpolydatin
is the main dietary source of trans-resveratrol in
red wine. Additionally, previous studies have shown that
trans-polydatin can inhibit platelet aggregation, improve microcirculation,
alleviate tissue-organ damage induced by ischemia
reperfusion, lower blood cholesterol, and suppress lipid peroxide
formation (5, 6).

[Hedgehog]

I wish I had taken part in this research because the article echoes a lot of things that I have been thinking about...

Although there is considerable evidence that transresveratrol
possesses strong biological activity, wine has a low
level of trans-resveratrol in comparison to its glucoside transpolydatin
(piceid, trans-3,5,40-trihydroxylstilbene-3-mono-D-glycoside).
In fact, the level of trans-polydatin in red wine is 10 times
greater than the level of trans-resveratrol (4 ). Therefore, transpolydatin
is the main dietary source of trans-resveratrol in
red wine. Additionally, previous studies have shown that
trans-polydatin can inhibit platelet aggregation, improve microcirculation,
alleviate tissue-organ damage induced by ischemia
reperfusion, lower blood cholesterol, and suppress lipid peroxide
formation (5, 6).

A number of people have been asking me where you can buy polydatin kingherbs.com is the place I'm familiar with. However, they don't do capsules...

[drmz]

The study in this topic points to this study:

Piceid administration might be an alternative to pure compound intake, as suggest by
Burkon and Somoza [15].

Quantification of free and protein-bound trans-resveratrol metabolites and identification of trans-resveratrol-C/O-conjugated diglucuronides - two novel resveratrol metabolites in human plasma.
Burkon A, Somoza V.

Deutsche Forschungsanstalt für Lebensmittelchemie, Garching, Germany.

The polyphenol trans-resveratrol (t-RES) is present as t-RES-3-O-beta-D-glycoside, termed piceid, in several plant-derived foods. Although data on the metabolism and on in vivo effects of t-RES have been reported, quantitative data on the metabolites formed after dietary intake of t-RES or piceid are still lacking. In this study, 85.5 mg of piceid per 70 kg of body weight (bw) were administered to healthy volunteers in a bolus dose. t-RES metabolites formed in plasma and urine were identified and quantified by LC-MS/MS, NMR, and HPLC-DAD analysis using chemically synthesized t-RES conjugate standards. In addition, the amount of t-RES metabolites bound noncovalently to plasma proteins was determined for the first time in humans. The metabolites identified and quantified were t-RES-3-sulfate, t-RES-3,4'-disulfate, t-RES-3,5-disulfate, t-RES-3-glucuronide and t-RES-4'-glucuronide, with t-RES-sulfates being the dominant conjugates in plasma and urine. Besides these metabolites, two novel t-RES-C/O-conjugated diglucuronides have been identified and quantified in plasma and urine. Moreover, it could be shown that up to 50% of the plasma t-RES-3-sulfate, t-RES-disulfates, and the novel t-RES-C/O-diglucuronides were bound to proteins. Total recovery of the dietary administered piceid in urine ranged between 13.6 and 35.7%

No time to read the study.

Edited by drmz, 01 January 2010 - 09:20 AM.