Ginkgo BilobavsNAC (N-Acetyl Cysteine)

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.

NAC provides cysteine, the rate-limiting substrate for glutathione (GSH) synthesis via gamma-glutamylcysteine ligase (GCLC) and glutathione synthetase (GSS). GSH is the primary intracellular antioxidant, essential for GPx and GST-mediated detoxification of reactive oxygen species in neurons. NAC also modulates glutamate via the cystine-glutamate antiporter (System Xc-, composed of xCT and 4F2hc) — NAC is deacetylated to cysteine, which exchanges for glutamate; the increased extracellular cystine is reduced to cysteine intracellularly, while the exchange increases extrasynaptic glutamate, which activates inhibitory mGlu2/3 autoreceptors on presynaptic terminals, reducing excessive glutamatergic signaling and compulsive behaviors. This glutamate modulation is the basis for psychiatric applications (OCD, addiction). NAC may also directly modulate NMDA receptors via redox sites.