5 replies to this topic

[malbecman]

Maybe this is why some people report GI distress when they start dosing from t-resveratrol (read the 1st two sentences of the abstract). They claimed to have synthesized this in multigram quantities, perhaps it will be available soon. At least the 3,5 dihydroxy form should be more water soluble.

It's from a reputable journal, I don't have access to the full article yet, however.

J Pharmacol Exp Ther. 2008 Dec 9. [Epub ahead of print]
Improved Anti-ulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice.
Guha P, Dey A, Sarkar B, Dhyani MV, Chattopadhyay S, Bandyopadhyay SK.
Dr. B.C. Roy Post Graduate Institute of Basic medical Sciences & IPGME&R, Kolkata, India.

In spite of its potential, use of trans-resveratrol as an anti-cancer drug is severely constrained due to its tendency to prolong gastric ulceration. We found that besides delaying ulcer healing, trans-resveratrol also aggravated acute gastric ulceration-induced by the non-steroidal anti-inflammatory drugs (NSAIDs) by reducing the synthesis of prostaglandin (PG)E2 via a specific inhibition of cyclooxygenase-1 (COX-1) that also hampered angiogenesis. However, for the first time we showed that 3'-5'-hydroxylated congener [(E)-HST-1] of trans-resveratrol, synthesized in multigram scale exerted potential chemotherapeutic property but was non-ulcerogenic in nature, rather moderately accelerated healing of indomethacin-induced gastric ulceration. HST-1 did not suppress COX-1, COX-2 expression and (PG)E2 synthesis, but reduced the level of inflammatory myeloperoxidase (MPO) activity. Healing augmented primarily through nitric oxide synthase (NOS) dependent pathway. HST-1 treatment induced endothelial NOS (eNOS) expression and reduced inducible NOS (iNOS) resulting in increased eNOS/iNOS ratio. Selective iNOS inhibitor (L-NIL) and nonselective NOS inhibitor (L-NAME) treatment revealed that eNOS could be the probable molecular switch to accelerate the indomethacin induced ulcer healing in HST-1 treated mice. Further, the anticancer effect of HST-1 on U937 and K562 leukemia cell lines was found to be significantly better than that of trans-resveratrol. Overall, these established HST-1 as a potentially better anti-cancer compound than trans-resveratrol considering it is devoid of any ulcerogenic side effects. In conclusion, for the first time we showed that a novel analog of trans-resveratrol, HST-1 was devoid of ulcerogenic adversative effects of trans-resveratrol but retained potentially better anticancer property.

PMID: 19066340

[malbecman]

Ok, I got the paper now, hooray! ;-)

[niner]

Interesting, malbecman. Even better anti-cancer activity with the new analog, but no ulcers. I guess that would mean less of an anti-inflammatory effect if they've wiped out all COX inhibition, but they don't say anything about NF-kB effects. I wonder if ulcers are a big issue because they are induced by chemotherapy, or are they more worried about NSAIDS? At any rate it's good to see people analoging around resveratrol. It wouldn't be legal as a supplement since it's not a natural product, right? Correct me if I'm wrong on that. Probably wouldn't be all that hard to import a few kg from China though, if you want to play Guinea Pig.

[geddarkstorm]

Well, it seems resveratrol doesn't cause ulcers (though if paired with advil, it can exasperate advil's horrible effects on the intestines according to one paper I saw but can no longer find... Otherwise, resveratrol usually decreases intestinal inflammation), but it slows their healing. Ulcers are weird. Or rather, the stomach is weird. It doesn't act like the rest of the body, as we can see where resveratrol and NSAIDS only make things worst, rather than increase healing as at least resveratrol can do in many other tissues. There's also a big debate over what really causes ulcers, and there's new evidence going around that some (maybe even most) ulcers are the result of a particular bacterial infection - so the lowering of inflammatory response by resveratrol and NSAIDS slowing infection clearing, and thus ulcer healing, makes complete sense. Otherwise, it doesn't as much, since inflammation usually causes damage in non-infected tissues, and healing begins once inflammation stops.

I hope they do some more experiments so we can see how well this analogue can mimic the main functions of resveratrol. It sounds very interesting so far.

Edited by geddarkstorm, 16 December 2008 - 05:49 AM.

[maxwatt]

Well, it seems resveratrol doesn't cause ulcers (though if paired with advil, it can exasperate advil's horrible effects on the intestines according to one paper I saw but can no longer find... Otherwise, resveratrol usually decreases intestinal inflammation), but it slows their healing. Ulcers are weird. Or rather, the stomach is weird. It doesn't act like the rest of the body, as we can see where resveratrol and NSAIDS only make things worst, rather than increase healing as at least resveratrol can do in many other tissues. There's also a big debate over what really causes ulcers, and there's new evidence going around that some (maybe even most) ulcers are the result of a particular bacterial infection - so the lowering of inflammatory response by resveratrol and NSAIDS slowing infection clearing, and thus ulcer healing, makes complete sense. Otherwise, it doesn't as much, since inflammation usually causes damage in non-infected tissues, and healing begins once inflammation stops.

I hope they do some more experiments so we can see how well this analogue can mimic the main functions of resveratrol. It sounds very interesting so far.

But it is also quite likely that such an analog will not activate Sirtuins, which is what made resveratrol attractive in the first place/

[geddarkstorm]

But it is also quite likely that such an analog will not activate Sirtuins, which is what made resveratrol attractive in the first place/

That's exactly what I'm hesitant about. If it doesn't do that, then it's pretty useless for anything other than cancer. Hopefully the researchers will think about that point and check it out.