Amentoflavone

 http://anabolicminds.com/forum/supplements/255669-coops-corner-7-a.html

For those of you who have never heard of Amentoflavone, let’s get right to the point before going into the details. Amentoflavone is a biflavanoid whose “claim to fame” is the ability to directly enhance strength. In addition to this, it has the added benefits of aiding with fat loss and improving insulin sensitivity, making it an optimal ingredient in any preworkout or fat burner.

Current products utilizing Amentoflavone (as far as I know, please feel free to post extras and I will edit the list):

PES Norcodrene
Applied Nutriceuticals Uncut
Applied Nutriceuticals Beta Test
Analyzed Supplements Amentomax
Komodo Katana
ANS Dilate
SAN MegaTron

Strength Gain

The final trigger in muscle contraction is an increase in calcium in the muscle cell. This calcium is stored in an organelle known as the sarcoplasmic reticulum and is released in response to a neural stimulus. The calcium binds to key muscle proteins that result in contraction, and it has been shown that the more calcium released into the muscle cell, the more force is produced.

Amentoflavone possesses the highly unique ability to increase calcium release; in fact, essentially only one other commonly found compound shares this mechanism: caffeine. Unlike caffeine though, Amentoflavone is 20 times more potent at increasing muscle calcium than caffeine [1]. This increase in muscular calcium concentration is part of the reason why caffeine is an ergogen (capable of improving exercise performance), and Amentoflavone achieves this effect in a more potent manner.

Fat Loss

Amentoflavone is a mixed Phosphodiesterase (PDE) inhibitor [2-7]. Many of you are familiar with forskolin, which derives its utility in fat loss from its ability to increase cAMP levels in appropriate tissues, specifically adipose (fat) tissue. And many of you are familiar with, say, ephedrine, which acts as a b2 agonist to ultimately increase levels of intracellular cAMP. The final common pathway with both forskolin and ephedrine is the increase in cAMP in fat cells, which results in the subsequent activity of various kinases and transcription factors in inducing cascades that promote lipolysis, or the breakdown of stored fat. As mentioned above, amentoflavone inhibits PDE, and PDE is responsible for the breakdown of cAMP. So by blocking PDE with amentoflavone, we increase cAMP and thus increase fat loss as well. Here’s a simplified model:

A “(-)” denotes the inhibition of an enzyme/pathway, while a “(+)” denotes stimulation of an enzyme or pathway. As you can see, amentoflavone acts downstream of both ephedrine and forskolin to block the PDE enzyme. In simple terms, you get a “double negative” at cAMP levels, resulting in a positive (net) increase. This results in stimulation of the next step: “fat loss.” 

Interestingly enough, each compound listed above (ephedrine, yohimbine, forskolin, amentoflavone) acts on a different step of the fat loss pathway, and in theory, these could all be combined for a synergistic effect. I am not suggesting this, but it’s an interesting take home point.

I now want to take a brief second to explain why Amentoflavone is in Norcodrene. In the above list with all the amentoflavone products, you will notice that they are all preworkouts except for Norcodrene, which is a fat burner. If we refer back to the diagram, you will notice that Norcodrene contains cirsiumplex and caffeine, which are also PDE inhibitors and would have additive effects with amentoflavone for fat loss. But more importantly, Norcodrene contains a beta-agonist, an alpha-2-antagonist (SA2A), and of course nomilean. The net result is complete synergy for bodyfat reduction, and this is why a lot of Norcodrene users don't just "feel" like their appetite is suppressed. Indeed, even people who keep their diet the same note a fairly rapid reduction in bodyweight. 

The beta agonist starts off the lipolysis cascade, the SA2A (alpha-2-antagonist) ensures that the usual feedback inhibition of this fat loss system does not occur, and amentoflavone, caffeine, and cirsiumplex all suppress PDE and ensure that cAMP levels (and thus the rate of fat loss) stays as high as possible. Adding forskolin-95 to Norcodrene would even further potentiate this synergy as per the above diagram.

Amentoflavone also inhibits Fatty Acid Synthase [8-10], therefore acting on the opposite side of the coin by preventing the body from forming new fatty acids.

Pumps

Of note, among other isoforms, Amentoflavone is also a PDE5 inhibitor (the target of drugs like Viagra), which ultimately results in vasodilation and can promote pumps during training.

Insulin Sensitivity

Also related to fat loss is the enzyme PTP1B, which is involved in insulin signaling. Inhibition of PTP1B is being investigated as a possible treatment for obesity and diabetes, and Amentoflavone is a PTP1B inhibitor [11]. For our purposes, all you really need to know about this pathway is that PTP1B inhibition should chiefly improve insulin sensitivity. Along the same lines, Amentoflavone has been shown to reduce circulating lipids (LDL/triglycerides) in vivo, making it of further potential benefit to obesity/diabetes/metabolic syndrome [12].

So that’s the quick and dirty summary of what amentoflavone may help with:
1. Increased strength
2. Improved fat loss
3. Improved “pumps” or vasodilation
4. Improved insulin sensitivity

I’ve seen a lot of questions being asked about this compound simply because it’s so new and people are downright unfamiliar with it. Hopefully this will clarify any issues moving forward. Feel free to post your questions or feedback.

I’d like to give credit to neuron for being the first person to really highlight the utility of Amentoflavone for the masses. Please read at your own convenience and spread the good word: High Tower Pharmacology.

I’ll also take requests for any future, layman’s-style articles on specific ingredients, but I figured I’d get this one done first since there have been so many threads lately.

References

1. Properties of amentoflavone, a potent caffei... [Eur J Pharmacol. 1999] - PubMed - NCBI - Properties of amentoflavone, a potent caffei... Eur J Pharmacol. 1999 - PubMed - NCBI
2. Inhibition of cAMP-phosphodiesterase by biflavone... [J Nat Prod. 1998] - PubMed - NCBI - Inhibition of cAMP-phosphodiesterase by biflavone... J Nat Prod. 1998 - PubMed - NCBI
3. Biflavones of Decussocarpus rospigliosii as phosp... [Planta Med. 2007] - PubMed - NCBI - Biflavones of Decussocarpus rospigliosii as phosp... Planta Med. 2007 - PubMed - NCBI
4. Inhibition of cGMP-phosphodiesterase-5 by biflavo... [Planta Med. 2006] - PubMed - NCBI - Inhibition of cGMP-phosphodiesterase-5 by biflavo... Planta Med. 2006 - PubMed - NCBI
5. Antimalarial and vasorelaxant constit... [Ann Trop Med Parasitol. 2007] - PubMed - NCBI - Antimalarial and vasorelaxant constit... Ann Trop Med Parasitol. 2007 - PubMed - NCBI
6. Vasorelaxation by amentoflavone isolated from Sel... [Planta Med. 2004] - PubMed - NCBI - Vasorelaxation by amentoflavone isolated from Sel... Planta Med. 2004 - PubMed - NCBI
7. Inhibition of human platelet cyclic AMP ph... [Biochem Pharmacol. 1986] - PubMed - NCBI - Inhibition of human platelet cyclic AMP ph... Biochem Pharmacol. 1986 - PubMed - NCBI
8. Fatty acid synthase inhibition by amentoflav... [Biol Pharm Bull. 2009] - PubMed - NCBI - Fatty acid synthase inhibition by amentoflav... Biol Pharm Bull. 2009 - PubMed - NCBI
9. Fatty acid synthase inhibition by amentoflavon... [Phytother Res. 2013] - PubMed - NCBI - Fatty acid synthase inhibition by amentoflavon... Phytother Res. 2013 - PubMed - NCBI
10. Inhibition of fatty acid synthase by amentoflavon... [Arch Virol. 2012] - PubMed - NCBI - Inhibition of fatty acid synthase by amentoflavon... Arch Virol. 2012 - PubMed - NCBI
11. Protein tyrosine phosphatase 1B inhibitory a... [Biol Pharm Bull. 2007] - PubMed - NCBI - Protein tyrosine phosphatase 1B inhibitory a... Biol Pharm Bull. 2007 - PubMed - NCBI
12. Antidyslipidemic and antioxidant activity of t... [Phytomedicine. 2012] - PubMed - NCBI - Antidyslipidemic and antioxidant activity of t... Phytomedicine. 2012 - PubMed - NCBI