Polygala TenuifoliavsSulbutiamine

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.

Sulbutiamine consists of two thiamine (vitamin B1) molecules connected by a disulfide bridge, conferring lipophilicity and efficient blood-brain barrier penetration via passive diffusion. In the brain, it is hydrolyzed to thiamine and increases thiamine diphosphate (TDP) levels—the cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, enzymes critical for glucose metabolism and the Krebs cycle. Sulbutiamine upregulates D1 dopamine receptors in the prefrontal cortex, possibly through reduced receptor internalization or increased expression. It modulates glutamatergic transmission (affecting NMDA/AMPA receptor function) and enhances cholinergic transmission. The anti-fatigue and memory-enhancing effects likely stem from improved neuronal glucose oxidation, increased ATP production, and enhanced dopaminergic and cholinergic tone in cognitive circuits.