Antidepressant Mechanisms in Traditional Herbal Medicine

Traditional herbal medicines have long been employed for mood disorders through a combination of neurochemical, neurotrophic and anti-inflammatory actions. Bioactive constituents from herbs such as Panax ginseng, Polygalae Radix and Acori Tatarinowii modulate monoamine neurotransmission, upregulate brain-derived neurotrophic factor (BDNF) and other neurotrophins, regulate the hypothalamic–pituitary–adrenal (HPA) axis and alleviate oxidative stress. Classical multi-herb formulations exemplify a systems-based approach, enhancing synaptic plasticity and neurogenesis while dampening glial-driven inflammation. By engaging multiple molecular targets, these preparations address the complex aetiology of depression, offering potential synergy with conventional therapies and emphasising the need for standardised clinical evaluation.

Research from Nature Portfolio

Optimised formulations of a classical decoction have demonstrated robust antidepressant efficacy in animal models of chronic stress. One investigation showed that a refined blend of Panax ginseng and Polygalae Radix restored hippocampal monoamine levels and upregulated nerve growth factor (NGF), BDNF and their receptors, resulting in increased dendritic spine density and improved behavioural outcomes in chronically stressed rats. A follow-on study compared different ratios of the same herbal series and found that compositions enriched in ginseng and Polygalae Radix achieved the greatest enhancement of neurotrophic signalling, directly correlating with reductions in depressive-like behaviours. Together, these studies illuminate how carefully balanced polyherbal mixtures synergistically target neurotrophic pathways and synaptic integrity.

Antidepressant Mechanisms in Traditional Herbal Medicine publication trend

The graph below shows the total number of articles in antidepressant mechanisms in traditional herbal medicine across all publications each year (not limited to Nature Index journals).

Technical terms

Astrocytes: Star-shaped glial cells that support neuronal function, regulate neurotransmitter uptake and contribute to neuroinflammatory responses.

Microglia: Resident immune cells of the central nervous system responsible for detecting pathogens and mediating inflammatory processes.

Brain-derived neurotrophic factor (BDNF): A protein that promotes neuronal survival, differentiation and synaptic plasticity, essential for mood regulation.

Hypothalamic–pituitary–adrenal (HPA) axis: A neuroendocrine network controlling stress responses via cortisol release, often dysregulated in depression.

Synaptic plasticity: The capacity of synapses to strengthen or weaken over time, critical for learning, memory and emotional resilience.

Neuroinflammation: Activation of glial cells and release of cytokines in the brain, which can disrupt neuronal circuits and contribute to depressive pathology.

References

1. TNF-α/TNFR1 activated astrocytes exacerbate depression-like behavior in CUMS mice. Cell Death Discovery (2024).
2. Pharmacological Mechanism and Drug Research Prospects of Ginsenoside Rb1 as an Antidepressant. Antioxidants (2025).
3. Mechanisms of Panax ginseng action as an antidepressant. Cell Proliferation (2019).
4. Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems. Frontiers in Pharmacology (2020).
5. A Chinese herbal decoction, reformulated from Kai-Xin-San, relieves the depression-like symptoms in stressed rats and induces neurogenesis in cultured neurons. Scientific Reports (2016).
6. Kai-Xin-San series formulae alleviate depressive-like behaviors on chronic mild stressed mice via regulating neurotrophic factor system on hippocampus. Scientific Reports (2017).
7. Kai‐Xin‐San, a Chinese Herbal Decoction Containing Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria, Stimulates the Expression and Secretion of Neurotrophic Factors in Cultured Astrocytes. Evidence-based Complementary and Alternative Medicine (2013).