Ginkgo BilobavsPolygala Tenuifolia

Ginkgo biloba extract (EGb 761) contains flavonoids (quercetin, kaempferol, isorhamnetin) and terpenoids (ginkgolides A, B, C, J and bilobalide). The flavonoids are potent antioxidants that scavenge superoxide, hydroxyl radicals, and peroxynitrite, and protect neurons from oxidative damage; they may also chelate iron. The terpenoids (ginkgolides and bilobalide) improve blood flow by antagonizing platelet-activating factor (PAF) at the PAF receptor, which reduces platelet aggregation, blood viscosity, and improves microcirculation in the brain. Bilobalide protects mitochondria and reduces apoptosis. Ginkgo modulates nitric oxide (NO) availability via endothelial nitric oxide synthase (eNOS) for vasodilation. It inhibits monoamine oxidase A and B (MAO-A, MAO-B), mildly elevating dopamine and serotonin. It may enhance cholinergic transmission and reduce amyloid aggregation.

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.