Hi Max. Referring to your thread regarding resveratrol having negative effects on arthritis, I'd like to ask you more in detail where you found this bit of information and how you can substantiate your claim. I have a bf that has been taking resveratrol for many years now and just recently he's had what could be the arthritis you referred to, but until a biopsy is performed, it's only specualtion for the moment. If there's any information you can lead me to pertaining to the negative effects of resveratrol on auto immune diseases, please let me know. Thanks!
Sherrie
There was a paper claiming that Sirt1 activation aggravated autoimmune diseases. Resveratrol activates Sirt1. Many of us speculated that resveratrol would therefor aggravate auto-immune diseases such as rheumatoid arthritis, and that Sirt1 suppressors such as Niacinamide (nicotinamide) would potentially be helpful for such conditions. Perhaps some of the negative effects people have reported for resveratrol are due to auto-immune responses after Sirt1 activation?
The situation is not that simple, as the abstract below should demonstrate. One could experiment with Sirt1 blockers such as quercetin or niacinamide to see if they alleviated the condition. This paper even claims that niacinamide can prevent type I diabetes:
<snip...below from study quote>
Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
I'm confused. If SIRT1 activation inhibits PARP1 and if quercetin/etc. inhibit SIRT1, then quercetin/etc. should result in more PARP1, hence promote autoimmune pathogensis.
Yet, as this study indicates, quercetin/etc. inhibit PARP1. Do they somehow do this, despite also inhibiting SIRT1?
http://jn.nutrition....act/137/10/2190...
Biochemical, Molecular, and Genetic Mechanisms
Dietary Flavones and Flavonoles Are Inhibitors of Poly(ADP-ribose)polymerase-1 in Pulmonary Epithelial Cells1<A name=RFN2>,2Liesbeth Geraets3,*, Harald J. J. Moonen4, Karen Brauers4, Emiel F. M. Wouters5, Aalt Bast3 and Geja J. Hageman4 3 Department of Pharmacology and Toxicology and 4 Department of Health Risk Analysis and Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands; and 5 Department of Respiratory Medicine, Academic Hospital Maastricht, 6202 AZ Maastricht, The Netherlands * To whom correspondence should be addressed. E-mail: l.geraets@farmaco.unimaas.nl <script type=text/javascript> . The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), which
was initially known to be highly activated by oxidative stress-induced
DNA strand breaks, has been shown to be involved in the pathophysiology
of acute and chronic inflammatory diseases. PARP-1 deficiency
in mice led to the discovery of its coactivating function in
the nuclear factor-kappa B-mediated gene expression and in addition,
pharmaceutical inhibition of PARP-1 was shown to reduce the
production of inflammatory mediators. In this study, the in
vitro PARP-1-inhibiting effect of various flavonoids was investigated.
The flavonoids myricetin, tricetin, gossypetin, delphinidin,
quercetin, and fisetin were identified as significant inhibitors
of the purified enzyme. Further evaluation of these compounds
in
N-methyl-
N'-nitro-
N-nitrosoguanidine-treated human pulmonary
epithelial cells showed that the formation of the poly(ADP-ribose)
polymers, as well as the decreased NAD
+ levels, was reduced
by quercetin, fisetin, and tricetin. Finally, IL-8 production
of LPS-stimulated human pulmonary epithelial cells could be
significantly reduced by these flavonoids. The results of this
study indicate that specific flavonoids have PARP-1-inhibiting
activity in addition to the earlier described antioxidant effects.
PARP-1 inhibition and preservation of cellular NAD
+ and energy
production could play a role in the antiinflammatory activity
of these specific flavonoids. In addition, these results indicate
additional mechanisms by which flavonoids can exert antiinflammatory
activity. Furthermore, these results indicate possibilities
to use food-derived flavonoids in the treatment of chronic inflammatory
diseases.
...
David