Panax Ginseng Protects Against Anxiety And Cognitive Impairment Following 72 Hours of Sleep Deprivation - PUBMED 2016

Remember, there are a bunch of ginsenosides and they all have different effects. Some are more calming. Some are more stimulating. The parts of the plant (leaf, root, stem, root hairs, etc.), species, cultivar, growing conditions, and harvest time all have huge effects on the amounts and ratios of the different ginsenosides. This is why we are pushing to stop grouping things together as all one thing in standardizations. The withanolides in ashwagandha all have drastically different effects. The bacopasides in bacopa do too. The same goes for a bunch of different things out there, but most of the time we group them all together. I think we are doing a disservice to plant extracts by grouping things together that have drastically different effects.

In ginseng, you can group the ginsenisides into two types: protopanaxatriols and protopanaxadiols. The protopanaxatriols are Rg1 and Re. The protopanaxadiols are Rb1, Rb2, Rc, Rd, and Rg3. Rg1 is actually a partial agonist of the glucocorticoid receptor, which modulates the "fight or flight" response. Being a partial agonist, it acts as a modulator. So in times of excess stress it brings it down, but activates it in times of calm. So it normalizes stress in a sense. Re significantly increase extracellular levels of acetylcholine and dopamine in both the hippocampus and the medial prefrontal cortex. This is likely responsible for some of the cognitive enhancing properties. These two are higher in Panax ginseng than American ginseng (Panax quinquefolius).

In American ginseng, the protopanaxadiols are higher. These ginsenosides have lower affinities for the glucocorticoid receptor (GR) and higher affinity for the estrogen receptor (ER). The study you posted is showing that they are modulating GABA through TNFR1 activation as well. This would make sense for why people consider American ginseng more calming than panax ginseng. However, plant part plays a big role as well. Panax ginseng leaf is much higher in Rg1, Re, and Rd, but lower in Rb1, Rc, Rb2. Ginseng root, on the other hand, has lower levels of Rg1 and Re, and pushes that balance toward Rb1, Rb1, Rc, and Rd. I have not personally done analytical work on different plant parts of American ginseng, but I would bet plant part plays a role in the balance in that species as well. To make it even more complex, growing conditions and harvest time have a big effect on the ginsenosides, too. So where you grow it and when you harvest it can drastically alter the ratios. This is why you can have so much variability when trying different products. If you just group them all together as total ginsenosides, you would never see these differences, though!