Polygala TenuifoliavsShilajit

The saponins (tenuigenin, polygalasaponins, onjisaponins) and oligosaccharide esters (3,6'-disinapoyl sucrose, tenuifolisides) have multiple neurological actions. They inhibit acetylcholinesterase (AChE) at the catalytic site, increasing synaptic acetylcholine and enhancing muscarinic M1/M4 and nicotinic receptor signaling. They promote BDNF and NGF expression via CREB and ERK/MAPK pathways, supporting neuroplasticity and neurogenesis in the hippocampus and subventricular zone. They modulate NMDA receptor function (possibly as positive allosteric modulators at the glycine site) and enhance long-term potentiation (LTP) via CaMKII and PKC. The anti-depressant effects involve monoaminergic modulation — increasing dopamine and norepinephrine via MAO inhibition or reuptake modulation — and HPA axis regulation (reducing CRH and cortisol). Tenuigenin may also activate TrkB receptors directly.

Fulvic acid is the primary bioactive, acting as an electron shuttle that donates and accepts electrons — enhancing mitochondrial electron transport chain efficiency by facilitating electron transfer at Complex I and II, similar to CoQ10 but through a different (non-enzymatic) mechanism. DBPs (dibenzo-alpha-pyrones) protect CoQ10 from oxidation by scavenging radicals, extending its functional life in the reduced ubiquinol form. The combination increases ATP production in mitochondria. Fulvic acid also chelates minerals (iron, zinc, magnesium) via carboxyl and phenolic groups, forming soluble complexes that transport across cell membranes via divalent metal transporter 1 (DMT1) and other channels, improving bioavailability. It has direct antioxidant effects (scavenging ROS) and anti-inflammatory effects through inhibition of complement C3 activation and NF-kB.