Brain health

The effects of Ginseng and its bioactive constituents on Brain Health: Review of Ginseng's benefits for Neuroprotection, Serotoninergic balance and Gabaergic support.

  • Introduction
  • Neuroprotection
  • Serotoninergic balance
  • Gabaergic support
  • Conclusion
  • Bibliographic references

Neurological disorders have become increasingly prevalent in the in the past few decades. Ranging from anxiety and depression to neurodegenerative diseases like Parkinson's or Alzheimer's, neurological impairments are arising as some of the most concerning consequence of modern lifestyles, making brain health a critical focus for nutraceutical applications.

At the same time, emerging research is pointing towards potent natural compounds as potential solutions to prevent and mitigate an large array of these neurological conditions. And Korean ginseng's ginsenosides, through their role in modulating key biochemical pathways related to inflammation, neurotransmitter balance, and neuronal health, could be one of them.

Neuroinflammation is a complex biological process that plays a vital role in protecting our nervous system. However, when this process becomes chronic, it can lead to a host of health issues, from mood imbalance to neurological disorders [1-2].

Multiple ginsenosides have been shown to have potent anti-inflammatory properties and neuroprotective effects. They are known to modulate the production and release of cytokines, which play a crucial role in the development of neuroinflammatory responses. Those effects are possible three main pathways:

Inhibition of NF-kappaB

Rare ginsenosides like Rh2 [3], Rk1 [4] and Rg3 [5], as well as some classical ones like Rd [6], Rg1 [7] and Rb1 [8], can modulate the activation of the NF-κB pathway, a signaling pathway involved in the production of pro-inflammatory cytokines. By inhibiting this physiological process, ginsenosides can reduce excessive neuroinflammation and its associated symptoms.

Activation of Nrf2

Rare ginsenosides like Rh2[9-10], Rk3[11] and Rk1[12], can activate the Nrf2 pathway, which plays a key role in the cellular defense system against oxidative stress and inflammation. Activation of this mechanism can enhance antioxidant and anti-inflammatory mechanisms, further reducing the harmful effects of chronic neuroinflammation [13-17].

Stimulation of BDNF

Rare ginsenosides like Rk1[18], Rh2[19], Rg3[20] and its classical precursor (Rb1[21]) can increase the expression of brain-derived neurotrophic factor (BDNF), a protein that promotes the growth and survival of neurons. BDNF has been found to play a crucial role in learning, memory, and neuroplasticity, and its decreased expression has been associated with several neurological disorders, including depression and Alzheimer's disease. By increasing BDNF expression, ginsenosides can promote brain health and cognitive function.


Neuroinflammation is at the heart of brain health, and ginsenosides have been shown to have potent anti-inflammatory and neuroprotective effects that can improve brain function and reduce the risk of developing these disorders. The existing evidence suggests that this natural compound could be a promising phytonutrient for promoting overall brain health and preventing neurodegenerative issues.

Serotonin is a neurotransmitter that plays a critical role in regulating mood, cognition, and behavior. It is synthesized from the amino acid tryptophan, which is exclusively obtained from our diet. However, tryptophan metabolism can be disrupted in a number of ways, leading to imbalance in serotonin levels that can contributes to several health issues.

Ginsenosides have been found to modulate serotonin balance by targeting several key pathways of tryptophan metabolism, avoiding disruption of serotonin supply :

Inhibition of Kynurenin pathway

Rare ginsenoside Rg3[22] and its classical precursor (Rb1[23]) have been reported to limit the activation of the kynurenine pathway and to inhibit its key enzyme: IDO. The Kynurenine pathway is a complex physiological process that has been implicated in a range of physiological processes, including inflammation and brain functions. By limiting excessive activation of the kynurenine pathway, Rg3 limits the risk of neuroinflammation and the overconsumption of tryptophan, allowing this amino-acid to be used for serotonin production instead of kynurenine production.

Activation of AhR pathway

Multiple ginsenosides have been identified as activators of the AhR pathway [24-26]. In addition, ginsenoside Rg1 was reported to increase the production of Indole derivatives by the gut microbiota [27], leading to an increased activation of the AhR pathway.

The AhR pathway is activated by a range of ligands including tryptophan metabolites. Once activated, the AhR pathway regulates gene expression and modulates a range of cellular processes, including inflammation, oxidative stress, and cellular metabolism.


By modulating tryptophan metabolism through the inhibition of Kynurenin pathway, ginsenosides are able to support serotoninergic balance, while supporting in the same time the immune system aspect of tryptophan metabolism through AhR activation.

GABAergic pathways are related to the network of neurons that utilize the neurotransmitter gamma-aminobutyric acid (GABA) and inhibit or reduce the activity of other neurons in the brain. Those pathways play a critical role in regulating a wide range of physiological and behavioral processes, including mood, anxiety, and stress. The GABAergic support is particularly important for mental health and well-being because it helps to prevent overstimulation of the nervous system, which can lead to feelings of anxiety and distress. This kind of support is usually considered to be at the core of a grounding effect, leading to a sense of being grounded in the present moment and avoid excessive nervosity.

Support GABA signal

Some rare ginsenosides, like Rg3[28] and CK[29] , have been reported to increase GABAergic signaling. This increase of GABA signal can be explained by different mechanisms including spontaneous release of GABA, or increase of GABA level.

Increase GABA Receptor expression

Some rare ginsenosides like Rg5 and Rk1 [30] , as well as a their precursor Rb1 [31], were reported to increase the expression of GABA receptors. By doing so, they can increase sensitivity of the GABAergic pathways and therefore support mental balance.


Ginsenosides are able to support GABAergic pathways leading to a grounding effect. Combined with the serotoninergic balance, ginsenosides offer a unique effect that favors mental well-being.

As our understanding of neurological health continues to deepen, it becomes increasingly clear that mitigating neuroinflammation and maintaining neurotransmitter balance is crucial in preserving brain health.

While further research is needed to fully understand their therapeutic potential, Korean ginseng and its bioactive compounds could well offer a natural, comprehensive and multi-target approach for evidence-based natural solutions to promote Brain Health, as show by their promising results on modulating neuroinflammation, supporting serotoninergic balance, and reinforcing GABAergic pathways.

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