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Natural Plant Polysaccharides for Depression: Antidepressant Mechanisms & Effects (2024 Review)

Depression is a complex mental health disorder that affects millions of people worldwide, presenting a significant challenge for current medical treatments due to various side effects and drug resistances associated with conventional antidepressants.

In response, researchers have turned their attention to natural plant polysaccharides, which have shown promising antidepressant effects through diverse mechanisms.

This exploration of natural resources for depression treatment not only broadens our understanding of the disorder’s intricacies but also paves the way for developing more effective and safer therapeutic options.


  1. Natural Plant Polysaccharides as Potential Antidepressants: Polysaccharides derived from plants possess a wide range of biological activities, including significant antidepressant effects, with minimal side effects compared to conventional drugs.
  2. Mechanisms of Action: These compounds work through various pathways, including the regulation of neurotransmitters, modulation of the hypothalamic-pituitary-adrenal (HPA) axis, reduction of neuroinflammation, and improvement of oxidative stress and gut microbiota balance.
  3. Evidence from Preclinical & Clinical Research: Although most current studies are preclinical, involving cellular and animal models, emerging clinical trials demonstrate the potential of polysaccharides in treating depression in humans.
  4. Future Research Directions: Further investigation into the specific mechanisms, optimization of clinical applications, and exploration of new therapeutic targets for polysaccharides are crucial for their development into viable antidepressant medications.

Source: Frontiers in Pharmacology (2024)

What are Plant Polysaccharides?

Polysaccharides are complex carbohydrates composed of long chains of monosaccharide units bonded together by glycosidic linkages.

They are found in a wide range of natural sources, including plants, fungi, and microorganisms, and have attracted attention for their diverse health benefits, including immunomodulatory, anti-inflammatory, antioxidant, and neuroprotective effects.

The potential of polysaccharides to aid in the treatment of depression is particularly compelling, given the multifactorial nature of this mental health disorder, which involves imbalances in neurotransmitters, chronic inflammation, oxidative stress, and dysregulation of the gut-brain axis.

Polysaccharides may help alleviate depression through several mechanisms:

  • Neurotransmitter Balance: They can influence the levels of key neurotransmitters like serotonin, dopamine, and norepinephrine, which play crucial roles in mood regulation.
  • Anti-inflammatory and Immunomodulatory Effects: Polysaccharides can reduce neuroinflammation, a significant contributor to depression, by modulating the immune response and decreasing the production of pro-inflammatory cytokines.
  • Antioxidant Properties: They combat oxidative stress by neutralizing free radicals and promoting the activity of antioxidant enzymes, protecting brain cells from damage.
  • Gut-Brain Axis Regulation: By influencing the composition of the gut microbiota, polysaccharides can affect the production of neuroactive compounds and inflammatory mediators that impact brain function and mood.

Polysaccharides differ from other supplements or components of plants due to their unique structural characteristics and the broad spectrum of their biological activities.

While other plant-derived compounds, such as flavonoids or alkaloids, may target specific biochemical pathways or receptors, polysaccharides often exert their effects through multiple mechanisms simultaneously.

This multifaceted approach is particularly beneficial for complex conditions like depression, where multiple physiological systems may be dysregulated.

Furthermore, the natural origin and general safety profile of polysaccharides make them an attractive option for individuals seeking alternative or complementary treatments for depression.

Major Findings: Antidepressant Mechanisms of Plant Polysaccharides (2024 Review)

Yu-He Yang et al. researched the nuanced and multifaceted effects of natural plant polysaccharides on depression, revealing their antidepressant potential through various biochemical and physiological pathways – below are some findings.

1. Neurotransmitter Regulation

Enhancement of Monoamine Levels: The paper highlights substantial evidence that certain polysaccharides can elevate the levels of central monoamine neurotransmitters, such as serotonin (5-HT), dopamine (DA), and norepinephrine (NE). This action is pivotal for the antidepressant effects, as deficiencies in these neurotransmitters are closely linked to the pathophysiology of depression.

Modulation of Neurotransmitter Receptors: Beyond increasing neurotransmitter levels, some polysaccharides also modulate the function of neurotransmitter receptors, thereby enhancing or inhibiting their activity. This nuanced regulation helps in restoring the delicate balance of excitatory and inhibitory signals crucial for mood stabilization.

2. HPA Axis Modulation

Normalization of Stress Hormones: The findings underscore the ability of polysaccharides to modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis, a critical regulator of the body’s stress response. By reducing the secretion of stress hormones like cortisol, polysaccharides can mitigate one of the biological underpinnings of stress-induced depression.

Restoration of Negative Feedback Mechanisms: Polysaccharides have been shown to restore the HPA axis’s negative feedback regulation, which is often impaired in depressive states. This restoration helps in maintaining homeostasis and reducing the overactivation of stress response pathways.

3. Neuroinflammation Reduction

Inhibition of Pro-inflammatory Cytokines: The paper details how polysaccharides exert significant anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines within the brain, such as TNF-α, IL-1β, and IL-6. This reduction in neuroinflammation is crucial, as chronic inflammation is a recognized contributor to the development and persistence of depression.

Modulation of Microglial Activation: Furthermore, specific polysaccharides target microglial cells, the brain’s resident immune cells, shifting their phenotype from a pro-inflammatory state to a more neuroprotective one. This shift reduces the inflammatory milieu of the brain, protecting neuronal health and function.

4. Oxidative Stress Improvement

Scavenging of Reactive Oxygen Species: The antioxidative properties of polysaccharides, capable of scavenging reactive oxygen species (ROS), play a significant role in their antidepressant effects. By reducing oxidative stress, these compounds protect neurons from oxidative damage, which is implicated in the pathophysiology of depression.

Enhancement of Antioxidant Defense Systems: Polysaccharides also enhance the body’s endogenous antioxidant defenses, including enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx). This bolstering of antioxidant defenses further contributes to the neuroprotective effects against oxidative stress.

5. Gut Microbiota Balancing

Influence on Gut Microbiota Composition: The paper presents evidence that polysaccharides can beneficially alter the composition of the gut microbiota. This modulation of gut bacteria not only influences gastrointestinal health but also impacts the gut-brain axis, offering a novel avenue for treating depression.

Production of Beneficial Metabolites: By influencing the gut microbiota, polysaccharides increase the production of short-chain fatty acids (SCFAs) and other metabolites that have positive effects on brain function and mood regulation.

6. Tryptophan Metabolism Regulation

Shifting Tryptophan Metabolism: An intriguing finding is the ability of polysaccharides to influence the metabolism of tryptophan, a precursor to serotonin. By shifting tryptophan metabolism towards serotonin synthesis rather than the kynurenine pathway, polysaccharides can increase serotonin availability, directly impacting depressive symptoms.

(Read: Polyphenols & Depression: Antidepressant Effects of Plant Compounds)

Plant Polysaccharides for Depression (2024 Review)

The primary aim of the paper was to explore and synthesize current research findings on the antidepressant effects of polysaccharides extracted from various natural plants.


  • Literature Review: The paper employs a comprehensive literature review methodology, gathering data from various scientific databases and publications. It focuses on studies that investigate the antidepressant effects of natural plant polysaccharides in both preclinical (animal models) and clinical settings.
  • Data Synthesis: Information is synthesized to highlight key findings regarding the pharmacological activities, experimental evidence, and proposed mechanisms of action of these polysaccharides. The review spans studies that elucidate the impact of polysaccharides on neurotransmitter regulation, the HPA axis, neuroinflammation, oxidative stress, and gut microbiota.


  • Neurotransmitter Regulation: Polysaccharides have been found to regulate the levels of key neurotransmitters involved in depression, such as serotonin, dopamine, and norepinephrine.
  • HPA Axis Modulation: Several polysaccharides demonstrate the ability to modulate the HPA axis, reducing the overproduction of stress hormones that are often linked to depression.
  • Neuroinflammation & Oxidative Stress: The compounds exhibit anti-inflammatory and antioxidant properties, mitigating neuroinflammation and oxidative stress, which are critical factors in the pathophysiology of depression.
  • Gut Microbiota Balance: Polysaccharides impact the composition of the gut microbiota, suggesting a role in improving depressive symptoms through the gut-brain axis.
  • Tryptophan Metabolism: Some polysaccharides may influence tryptophan metabolism, steering it towards serotonin synthesis and away from pathways that could exacerbate depression.


  • Preclinical Focus: The majority of studies reviewed are preclinical, relying on animal models to infer the antidepressant effects of polysaccharides. There is a notable gap in clinical research that directly assesses these effects in human populations.
  • Mechanism Specificity: While the paper outlines several mechanisms through which polysaccharides may exert their antidepressant effects, the specificity of these mechanisms and their direct contribution to therapeutic outcomes remain partially elucidated.
  • Complexity of Depression: The multifactorial nature of depression means that targeting it requires a multifaceted approach. The paper acknowledges the complexity of accurately determining which mechanisms are most beneficial in treating depression.
  • Variability in Polysaccharide Composition: There is significant variability in the composition and structure of polysaccharides extracted from different sources, which may affect their biological activity and efficacy as antidepressants. This variability is a challenge for standardizing treatment approaches.

5 Promising Plant Polysaccharides for Depression

The review highlights several natural plant polysaccharides that have shown promising antidepressant effects through various mechanisms of action.

These compounds have been studied in preclinical and, in some cases, early clinical settings, providing insights into their potential efficacy and underlying mechanisms.

Below, we summarize the most promising natural plant polysaccharides, their evidence level/efficacy, and mechanisms of action.

1. Lycium Barbarum Polysaccharides (LBP)

Evidence Level/Efficacy: Preclinical studies have extensively demonstrated LBP’s antidepressant effects, with emerging clinical trials suggesting potential efficacy in humans.

Mechanisms of Action:

  • Modulates neurotransmitter levels, particularly serotonin and dopamine, enhancing mood regulation.
  • Exerts neuroprotective effects by reducing oxidative stress through antioxidant activity.
  • Influences the gut-brain axis by altering gut microbiota composition and increasing SCFA production.

2. Polygonatum Sibiricum Polysaccharides (PSP)

Evidence Level/Efficacy: Predominantly preclinical evidence supports PSP’s antidepressant effects, with studies indicating significant behavioral and biochemical improvements in animal models of depression.

Mechanisms of Action:

  • Regulates HPA axis activity, reducing cortisol levels and mitigating stress-induced depressive symptoms.
  • Decreases neuroinflammation by lowering pro-inflammatory cytokine levels in the brain.
  • Modulates gut microbiota, potentially affecting the gut-brain axis and improving depressive outcomes.

3. Astragalus Polysaccharides (APS)

Evidence Level/Efficacy: APS has been supported by preclinical studies for its antidepressant properties, highlighting its broad pharmacological activities.

Mechanisms of Action:

  • Enhances immune function and reduces inflammation, indirectly supporting mood regulation.
  • Protects against oxidative stress by increasing the activity of antioxidant enzymes and reducing oxidative markers.
  • May modulate neurotransmitter systems, though specific mechanisms require further elucidation.

4. Ganoderma Lucidum Polysaccharides (GLP)

Evidence Level/Efficacy: Preclinical research has demonstrated GLP’s potential in treating depression, with its broad range of biological activities suggesting a multifaceted mechanism of action.

Mechanisms of Action:

  • Exhibits anti-inflammatory properties by modulating microglial activation and cytokine production.
  • Acts as an antioxidant, reducing oxidative stress and protecting neuronal health.
  • Influences neurotrophic factors, potentially enhancing neurogenesis and neural repair mechanisms.

5. Ginkgo Biloba Polysaccharides (GBP)

Evidence Level/Efficacy: GBP shows promise in preclinical studies, with antidepressant effects observed in various animal models of depression.

Mechanisms of Action:

  • Modulates the neurotransmitter systems, particularly serotonin and norepinephrine, to improve mood and cognitive function.
  • Reduces oxidative stress and neuroinflammation, protecting against neuronal damage.
  • May influence the gut microbiota composition, though the exact effects on the gut-brain axis are yet to be fully understood.

Conclusion: Plant Polysaccharides for Depression

The paper’s comprehensive exploration into the antidepressant effects of natural plant polysaccharides offers promising insights into alternative treatments for depression, a complex and multifaceted mental health disorder.

By elucidating the mechanisms through which these polysaccharides exert their effects—ranging from neurotransmitter regulation and HPA axis modulation to reducing neuroinflammation, oxidative stress, and balancing gut microbiota—the research highlights the potential of these compounds in addressing the diverse biological underpinnings of depression.

Despite the promising preclinical evidence, the paper underscores a significant gap in clinical research, pointing to the need for rigorous clinical trials to validate the efficacy and safety of polysaccharides in human populations.

Furthermore, the variability in polysaccharide composition and structure among different plants suggests a challenge in standardizing treatments, indicating that future research should aim to identify and characterize the most effective polysaccharides for depression therapy.

The paper concludes by advocating for a multifaceted approach to depression treatment, incorporating natural plant polysaccharides as part of a broader, holistic strategy that considers the complex biochemistry of depression.

Overall, advancing our understanding of natural plant polysaccharides and their role in treating depression could lead to the development of novel, more effective, and less side-effect-prone therapeutic options for individuals suffering from this debilitating condition.


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