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Saffron Extract (Affron) Reduces Stress via HPA Axis & Neuroplasticity in Rats (2023 Study)

In a world increasingly burdened by the psychological strains of modern living, the quest for effective and safe treatments for stress-related symptoms has never been more urgent.

A recent study evaluated the stress-mitigating properties of Affron® – a Saffron extract – in animal models, revealing its potent effects on the body’s stress response systems, including the HPA axis.


  1. Saffron Extract as a Stress Reliever: The standardized saffron extract, Affron®, has shown significant potential in alleviating stress by modulating the body’s stress response mechanisms.
  2. Impact on HPA Axis Regulation: Affron® effectively normalizes the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, a central player in the body’s response to stress.
  3. Enhancement of Neuroplasticity: Beyond regulating stress responses, Affron® has been demonstrated to enhance neuroplasticity, indicating its broader therapeutic potential.
  4. Research-Backed Efficacy: Through rigorous scientific study, including animal models, Affron® has been validated as an effective, natural remedy for combating stress and improving mental well-being.

Source: Nutrients (2023)

What is Saffron Extract?

Saffron extract, and specifically Affron®, is considered a potential natural remedy for the treatment of stress related conditions.

Derived from the stigmas of the Crocus sativus flower, saffron has been celebrated for centuries not only as a culinary spice but also for its medicinal properties.

A Natural Antidote to Stress

Saffron extract contains a rich combination of bioactive compounds, including crocin, safranal, crocetin, and picrocrocin, which are believed to contribute to its therapeutic effects.

Research suggests these compounds interact with the central nervous system, potentially influencing mood, anxiety, and stress levels.

The antidepressant and anxiolytic properties of saffron extract have been attributed to its ability to modulate neurotransmitters such as serotonin, dopamine, and norepinephrine, which play critical roles in regulating mood and stress responses.

What is Affron®?

Affron® is a standardized extract of saffron designed to ensure consistent potency and efficacy in every dose.

It has been the subject of various clinical trials aiming to assess its impact on mood, anxiety, and stress in humans.

Mechanisms of Action

  • HPA Axis Regulation: Affron® has shown promise in normalizing the function of the hypothalamic-pituitary-adrenal (HPA) axis, a key stress response system in the body. By modulating this axis, Affron® may help mitigate the physiological impacts of stress.
  • Enhancement of Neuroplasticity: Beyond its effects on mood and anxiety, Affron® may promote neuroplasticity, the brain’s ability to form new neural connections. This could support cognitive function and resilience against stress-induced neurological changes.
  • Neurotransmitter Modulation: Affron®’s potential to influence levels of critical neurotransmitters offers another mechanism by which it may exert its stress-relieving effects, contributing to improved mood and reduced anxiety.

Major Findings: Effects of Saffron Extract (Affron®) on Stress in Animal Models (2023)

Chae-Young Kim et al. tested the effects of a standardized saffron extract, Affron® for stress alleviation and enhancement of neuroplasticity in rats – below are the findings.

1. HPA Axis Regulation

Repetitive administration of Affron® at doses of 100 mg/kg and 200 mg/kg effectively normalized HPA axis dysregulation in Wistar rats subjected to unpredictable chronic mild stress (CMS).

The study found that Affron® administration led to significant reductions in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, which are key indicators of stress and HPA axis activity.

This normalization suggests that Affron® has a stabilizing effect on the HPA axis, potentially mitigating the physiological impacts of stress.

2. Enhancement of Neuroplasticity

Increased doses of Affron® demonstrated a dose-dependent improvement in markers of neuroplasticity, notably brain-derived neurotrophic factor (BDNF).

BDNF plays a critical role in neuronal survival, synaptic function, and neurogenesis.

The study observed a significant increase in BDNF levels following Affron® administration, indicating enhanced neuroplasticity and potentially improved brain health and function in response to stress.

3. Impact on Stress-Related Behaviors

Affron® administration resulted in significant behavioral changes in rats, indicative of reduced stress and depression-like symptoms.

The sucrose preference test (SPT), a measure of anhedonia (loss of pleasure), showed that Affron® treated groups exhibited a significant increase in sucrose consumption compared to the stress-induced group.

This suggests an improvement in stress-induced anhedonia, aligning with the alleviation of depression-like behaviors.

4. Modulation of Stress Hormones & Neurotransmitters

Affron® affected the levels of stress-related hormones and neurotransmitters, including a reduction in ACTH and CORT levels.

Beyond the normalization of HPA axis indicators, the study also hinted at the potential modulation of serotonin (5-HT) levels, although these findings were less conclusive.

The precise impact of Affron® on neurotransmitter systems warrants further investigation but suggests a broad-spectrum effect on stress-related neurochemical pathways.

5. Neuroprotective & Anti-Stress Effects

The study highlights the neuroprotective and anti-stress effects of Affron®, underlined by its action on the HPA axis and neuroplasticity enhancement.

By reducing the expression of stress hormones and enhancing markers of brain health and plasticity, Affron® exhibits a comprehensive approach to mitigating stress and its physiological impacts.

This dual action positions Affron® as a potentially powerful agent for stress resilience and mental health support.

Standardized Saffron Extract on Stress & Neuroplasticity in Rats (2023 Study)

The objective of the study was to investigate the effects of a standardized saffron extract, Affron®, on stress alleviation and neuroplasticity enhancement using an unpredictable chronic mild stress (CMS) model in Wistar rats.


  • Test Substance: Affron® was suspended in distilled water and administered orally at doses of 100 mg/kg and 200 mg/kg daily for three weeks.
  • Animals & Experimental Groups: Forty male Wistar rats were divided into four groups: control, stress-induced (CMS without treatment), and two treatment groups subjected to CMS and treated with either 100 mg/kg or 200 mg/kg of Affron®.
  • CMS Protocol: The CMS model involved a variety of stress-inducing procedures applied unpredictably over four weeks to induce stress conditions.
  • Evaluation Methods: The study assessed the effects of Affron® through several parameters, including hypothalamic gene expression, levels of stress hormones (ACTH and CORT), and the sucrose preference test (SPT) as a measure of anhedonia. Additional assessments included immunohistochemistry for neuroplasticity markers and ELISA assays for hormone levels.


  • HPA Axis Regulation: Affron® significantly normalized HPA axis dysregulation, as evidenced by reduced ACTH and CORT levels in treated groups compared to the stress-induced group.
  • Neuroplasticity Enhancement: There was a dose-dependent increase in markers of neuroplasticity, particularly BDNF, indicating enhanced brain health and function following Affron® treatment.
  • Behavioral Improvements: Rats treated with Affron® showed significant improvements in behaviors associated with stress and depression, including increased sucrose consumption in the SPT.
  • Hormonal & Neurotransmitter Modulation: The study reported a modulation of stress-related hormones, with Affron® treatment leading to a reduction in ACTH and CORT levels. The impact on serotonin (5-HT) levels was noted, although not definitively conclusive.


  • Species & Model Limitations: The use of Wistar rats and the CMS model, while informative, may not fully replicate the complexity of human stress responses and depressive disorders.
  • Dose-Response Relationship: While the study identified dose-dependent effects of Affron®, the optimal dosage for therapeutic use in humans remains to be determined.
  • Neurotransmitter Effects: The potential modulation of neurotransmitter systems, including serotonin, was not conclusively determined, indicating a need for further research to clarify these effects.
  • Generalizability to Humans: The findings, though promising, are derived from an animal model. Translational research is needed to confirm the efficacy and safety of Affron® in human populations.

Safely Trying Saffron Extract for Stress & Anxiety

Trying saffron extract as a means to reduce or alleviate stress involves careful consideration to ensure it’s done safely and effectively.

1. Consult a Healthcare Professional

Before beginning any new supplement regimen, especially for stress management, it’s crucial to consult with a healthcare provider.

This is particularly important if you are currently taking medication, pregnant, breastfeeding, or have underlying health conditions.

A healthcare professional can provide personalized advice and ensure that saffron extract does not interact with any medications or conditions.

2. Choose a High-Quality Saffron Extract

Look for standardized saffron extract supplements, like Affron®, which guarantee a consistent dose of the active compounds in saffron.

Ensure the product is third-party tested for purity and potency, verifying that what’s on the label is what’s in the bottle.

3. Start with Recommended Dosages

Begin with the lowest recommended dose to assess your body’s response. The typical effective dose for stress and mood improvement is often found between 15mg to 30mg of saffron extract, taken once or twice daily.

Do not exceed the recommended dosage on the product label or the advice provided by your healthcare provider.

4. Monitor Your Body’s Response

Pay attention to how your body reacts to the saffron extract over time. Note any changes in your stress levels, mood, and overall well-being.

Be aware of potential side effects, although rare, which can include dry mouth, dizziness, or gastrointestinal issues. If you experience any adverse reactions, stop taking the supplement and consult your healthcare provider.

5. Maintain a Balanced Approach

Consider saffron extract as part of a holistic approach to stress management, including healthy eating, regular physical activity, adequate sleep, and mindfulness practices.

Natural supplements like saffron extract can complement these lifestyle choices but should not be relied upon as a sole treatment for stress.

6. Evaluate Progress

After a few weeks of consistent use, evaluate whether the saffron extract has contributed to your stress relief efforts.

Discuss your experiences with your healthcare provider, especially if you haven’t noticed any benefits, to determine if you should continue using the supplement or explore alternative stress management strategies.

Conclusion: Affron (Saffron Extract) for Stress

The study on Affron®, a standardized saffron extract, underscores its promising role in mitigating stress and enhancing neuroplasticity, marking a significant advance in the search for natural mental health remedies.

By demonstrating a potent effect on the regulation of the HPA axis and the promotion of neuroplasticity in animal models, Affron® offers a potential pathway to improving human mental health and resilience against stress.

The findings highlight the therapeutic value of natural compounds in addressing complex mental health challenges, encouraging further research into their mechanisms of action and benefits.

However, translating these results to human applications necessitates rigorous clinical trials to ascertain optimal dosages, safety profiles, and efficacy across diverse populations.

As the global community continues to grapple with increasing stress and mental health issues, Affron® represents a hopeful addition to the arsenal of interventions promoting mental well-being.

Overall, the study paves the way for integrating scientifically backed natural remedies into holistic mental health strategies, potentially transforming approaches to stress, anxiety, and depression treatment.


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