2 replies to this topic

[Hedgehog]

Mitochondrial damage is often both the cause and outcome of cell injury resulting from a variety of toxic insults, hypoxia or trauma. Increasing mitochondrial biogenesis following renal proximal tubular cell (RPTC) injury accelerated the recovery of mitochondrial and cellular functions (Rasbach and Schnellmann, 2007a). However, few pharmacological agents are known to increase mitochondrial biogenesis......
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Daidzein and formononetin induced the expression of SIRT1 in RPTC and the activation of recombinant SIRT1 while DCHC and 7-C only induced the activation of recombinant SIRT1. In contrast, genistein, biochanin A, 4',7-D, and 5,7,4'-T only increased SIRT1 expression in RPTC. We have identified a series of substituted isoflavones that produce mitochondrial biogenesis through PGC-1alpha and increased SIRT1 activity and/or expression, independent of the estrogen receptor. Furthermore, different structural components are responsible for the activities of isoflavones:

• the hydroxyl group at position 7 is required SIRT1 activation
• A hydroxyl group at position 5 blocks SIRT1 activation
• the loss of the phenyl ring at position 3 or the 4' hydroxy or methoxy substituent blocks increased SIRT1 expression.

http://www.ncbi.nlm....pt=AbstractPlus

So do any other compounds fall into the blockage of activation of SIRT1 such as metabolites of quercetin or other compounds of interest?

This article is 41 pages LONG!

[treonsverdery]

anything that Promotes Mitochondrial Biogenesis is of value; that is a well worded search item with a bunch of items at pubmed
like

R-alpha-Lipoic acid and acetyl-L: -carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes

PPARgamma coactivator-1alpha (PGC-1alpha) , a "master switch" which induces mitochondrial biogenesis by supporting the transcriptional activity of the nuclear respiratory factors, may largely account for the diminished oxidative capacity of subjects prone to insulin resistance. Thus, feasible measures which up-regulate PGC-1alpha may be useful for preventing and treating insulin resistance and obesity. These may include exercise training, metformin and other agents which stimulate AMP-activated kinase, high-dose biotin, and PPARdelta agonists. Drugs which are specific agonists for PPARdelta show remarkable efficacy in rodent models of insulin resistance, diabetes, and obesity, and are currently being evaluated clinically. Phytanic acid, a branched-chain fatty acid found in omnivore diets, can also activate PPARdelta


have the embryologic developmental compounds been characterized

thats a way of saying: the way coconut milk is full of embryogenic chemicals that make plants start growth programs; various fetal as well as placental cytokines do similar things with mammals; I wonder if human placental or fetal cytokines Promote Mitochondrial Biogenesis

anyway much appreciated

Nature paper about Glamorous new chemical three orders of magnitude more powerful than resveratrol
http://www.ncbi.nlm....Pubmed_RVDocSum
Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival10, 11, 12, 13, 14. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol

Edited by treonsverdery, 14 February 2008 - 06:16 AM.

[Hedgehog]

Scheme 1 Summary of the cellular metabolism of quercetin and its O-methylated metabolites

O-methylated forms of quercetin associate with fibroblasts to a greater extent than does quercetin, whereas the glucuronide (Q-glucuronide) does not enter cells. Quercetin and 3´-O-methyl quercetin (3OMeQ) undergo oxidative metabolism within the cell to yield as yet unidentified intermediates, and a small amount of 4´-O-methyl quercetin (4OMeQ) is demethylated. Quercetin o-quinone (Q o-quinone) reacts with GSH to form a 2´-glutathionyl conjugate. Both the GSH conjugate and oxidative products are exported from cells.


http://www.biochemj....3/bj3720173.htm

Let me know if the image doesn't work...


Our data suggest that quercetin and its two O-methylated metabolites may provide protection against oxidatively induced cellular damage in vivo. Although the O-methylated metabolites were less efficacious in our fibroblast model, it should be noted that in vivo they would be present at greater concentrations than quercetin aglycone. The precise mechanism of the protective action observed here remains unclear; however, effects may be mediated by the cellular metabolism of these compounds (Scheme 1). The protective properties of the flavonols seemed to be due to the original compounds to which the cells were exposed; however, at higher exposure concentrations, at which quercetin and 3´-O-methyl quercetin showed some toxicity towards the cells, this could be mediated by compounds such as M1, M2 and 2´-glutathionyl quercetin that are formed intracellularly. The inability of the glucuronide to exert protection is almost certainly linked to its inability to associate with the cells. Further investigations are necessary to elucidate the precise mechanisms of action of these compounds.