J147 was recently in the news as a treatment for Alzheimer's and a potential anti-aging drug, but the press releases were sparse on details. There were photos of a strain of mice bred to age rapidly, looking svelt and young when compared to controls.
This is what seems to be known about J147's mechanism of action: induces neurotrophic factors NGF (nerve growth factor) and BDNF. That is about all, the mice seemed healthier than the controls. Perhaps it is over-hyped?
Dihydromyricetin is well known as an anti-intoxicant, via GABA antagonism: it binds to GABA receptors, blocking alcohol from binding, but not activating them, But Dihudromyricetin (DHM) has another effect: it stimulates irisin via PGC-1alpha, which causes release of BDNF in the brain
Sounds a bit like J147t there are more studies on DHM than on J147. In addition, DHM has been called an exercise mimetic in that it induces conversion of fat to brown (energy burning) fat, as does exercise. There are also studies showing DHM is a liver protectant, improves glucose metabolism, and has anti-cancer properties.
DHM is available on Amazon, at reasonable prices and appears to be quite safe. The available J147 substances are questionable as to identity, and seem to be at best inactive substances. Plus they are quite expensive.
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Irisin, derived from FNDC5, is an exercise-induced myokine that can stimulate the 'browning' of white adipose tissue, which is regulated by peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α). Dihydromyricetin (DHM), a natural flavonoid, exerts its activities through PGC-1α activation. Here, we explored whether DHM could mimic the effects of exercise on irisin secretion. DHM administration increased circulating irisin in rats and humans. Notably, the serum irisin level had a greater correlation to the level of circulating DHM than to the amount of exercise. DHM treatment upregulated PGC-1α and FNDC5 expression, enhanced energy metabolism, as evidenced by NMR-based metabonomics analysis, and partially abolished the suppressive effects of Pgc-1α siRNA on FNDC5 expression. These results suggest that DHM can stimulate irisin secretion partially via the PGC-1α pathway. As a potent exercise mimetic, DHM is expected to benefit patients suffering from metabolic diseases, especially those who cannot undergo rigorous exercise.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Dihydromyricetin (DHM); FNDC5; Irisin; Myokine; PGC-1α
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Exercise produces many beneficial effects on brain health, in part by increasing hippocampal BDNF levels; however, the mechanism underlying BDNF gene regulation remains unknown. In this issue of Cell Metabolism, Wrann et al. (2013) show that exercise induces hippocampal Bdnf expression by stimulating expression of FNDC5, the precursor of irisin, via the transcriptional complex PGC-1α/Errα.
Copyright © 2013 Elsevier Inc. All rights reserved.
- Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. [Cell Metab. 2013]
