There are a whole host of studies examining the effects of Amentoflavone on various neurological endpoints. Without going into each one individually, research highlights will be presented.
Amentoflavone interacts with the GABA-A receptor by acting as a negative modulator. This would produce a central stimulant effect by inducing wakefulness/alertness. Amentoflavone uptake into the CNS is limited by P-glycoprotein, an efflux pump that pumps specific compounds back outside of the CNS. There are numerous ways to overcome the P-glycoprotein transporter; a very well-documented one is by consuming grapefruit or its constituents.
In addition, amentoflavone has demonstrated antidepressant and anxiolytic (anti-anxiety) effects in vivo by interacting with not only the GABA-A receptor, but also the serotonin and alpha-adrenergic receptors. In fact, of all the tested constituents of St. John’s Wort (a known antidepressant/anti-anxiety plant), amentoflavone displayed the strongest anxiolytic activity.
Summary: CNS stimulant, anxiolytic, anti-depressant
Determinants of amentoflavone interaction at... [Eur J Pharmacol. 2005] - PubMed - NCBI
Inhibition of benzodiazepine binding in vitr... [Pharm Acta Helv. 1997] - PubMed - NCBI
Biflavones from Rhus species with affinity ... [J Ethnopharmacol. 2006] - PubMed - NCBI
Semisynthetic preparation of amentoflav... [Bioorg Med Chem Lett. 2003] - PubMed - NCBI
Transport of amentoflavone across the blood-brain... [Planta Med. 2002] - PubMed - NCBI
Antidepressant and anxiolytic effect... [Pharmacol Biochem Behav. 2012] - PubMed - NCBI
Review on plants with CNS-effects used in t... [J Ethnopharmacol. 2008] - PubMed - NCBI
Effects of St. John's wort extract and single con... [Planta Med. 2006] - PubMed - NCBI
Isolation of amentoflavone from Selaginella rupes... [Planta Med. 1981] - PubMed - NCBI
Fatty Acid Synthase Inhibition
Fatty acid synthase, as the name implies, is responsible for the endogenous synthesis of fatty acids in humans. It is currently a drug target for metabolic syndrome. In at least three separate trials, amentoflavone has demonstrated the ability to inhibit fatty acid synthase, and thus fat production.
Summary: Reduced fatty acid synthesis
Fatty acid synthase inhibition by amentoflav... [Biol Pharm Bull. 2009] - PubMed - NCBI
Fatty acid synthase inhibition by amentoflavon... [Phytother Res. 2013] - PubMed - NCBI
Inhibition of fatty acid synthase by amentoflavon... [Arch Virol. 2012] - PubMed - NCBI
Phosphodiesterase (PDE) Inhibition
PDE is the enzyme responsible for breaking down cAMP/cGMP. cAMP/cGMP promote smooth muscle relaxation (vasodilation; this is how PDE5 inhibitors help with erectile dysfunction) and lipolysis. Indeed, Forskolin has documented lipolytic activity by increasing cAMP levels via increased cAMP production. PDE inhibition, as with amentoflavone, hits the opposite side of the coin: reduced cAMP breakdown. By increasing cAMP levels, amentoflavone can synergize with adrenergic agonists (i.e. b-agonists) because second messenger pathways follow the rule of amplification.
Amentoflavone inhibits a broad array of PDE isoforms, and it is the most potent inhibitor out of all tested flavonoids in Ginkgo biloba. Further, of all tested constituents of Allanblackia monticola, Amentoflavone was the strongest vasodilator, inhibiting norepinephrine-induced vasoconstriction by a whopping 35%.
Summary: Increased lipolysis (fat loss) and increased vasodilation
Inhibition of cAMP-phosphodiesterase by biflavone... [J Nat Prod. 1998] - PubMed - NCBI
Biflavones of Decussocarpus rospigliosii as phosp... [Planta Med. 2007] - PubMed - NCBI
Inhibition of cGMP-phosphodiesterase-5 by biflavo... [Planta Med. 2006] - PubMed - NCBI
Antimalarial and vasorelaxant constit... [Ann Trop Med Parasitol. 2007] - PubMed - NCBI
Vasorelaxation by amentoflavone isolated from Sel... [Planta Med. 2004] - PubMed - NCBI
Inhibition of human platelet cyclic AMP ph... [Biochem Pharmacol. 1986] - PubMed - NCBI
Muscular Strength and Endurance
One well-documented mechanism of increasing exercise performance is vasodilation, which helps supply (oxygen; waste removal) meet the demand of exercising muscle tissue (hypoxia; metabolic waste accumulation). Amentoflavone has a well-documented effect on vasodilation as described above.
In addition to this, Amentoflavone provides a relatively unique mechanism for increasing power output: increased Ca2+ release from the sarcoplasmic reticulum. By increasing intracellular Ca2+ downstream of the signal for muscle contraction, binding to troponin-C is increased and the force of muscular contraction, on a cell-by-cell basis, also increases.
Caffeine acts via a similar mechanism to increase strength output, and researchers found that not only does Amentoflavone likely bind to the caffeine-binding site, but it does so with 20 times greater potency than caffeine.
Summary: Improved strength (Ca2+ release) and improved endurance (vasodilation)
Properties of amentoflavone, a potent caffei... [Eur J Pharmacol. 1999] - PubMed - NCBI
Insulin Sensitivity/GDA - PTP1B inhibition
PTP1B is an enzyme involved in insulin signaling, and inhibition of PTP1B is being investigated as a possible treatment for obesity and diabetes. PTP1B inhibition will chiefly improve insulin sensitivity by augmenting insulin’s actions within the cell at a lower circulating level of insulin. This is a fairly novel approach to improving insulin sensitivity and will continue to be investigated.
Summary: Improved insulin sensitivity
Protein tyrosine phosphatase 1B inhibitory a... [Biol Pharm Bull. 2007] - PubMed - NCBI
Amentoflavone has been shown in vivo to reduce circulating lipids (LDL/TG), making it of further benefit to obesity/diabetes/metabolic syndrome.
Summary: Reduced lipids
Antidyslipidemic and antioxidant activity of t... [Phytomedicine. 2012] - PubMed - NCBI
Credit and thanks to neuron: http://hightowerpharmacology.blogspot.com/2012/09/future-pharmacy-amentoflavone.html