Animal study finds that saffron extract may support resiliency to stress


A recent animal study found that a proprietary saffron extract may help manage stress by regulating the HPA axis.

Saffron. Image courtesy of Pharmactive.

Saffron. Image courtesy of Pharmactive.

A recent animal study1 found that a proprietary saffron extract may help manage stress by regulating the hypothalamic–pituitary–adrenal axis (HPA axis), which is associated with fight or flight response. In the study, researchers employed the unpredictable chronic mild stress animal model to investigate the extract’s (Affron, from Pharmactive, based in Madrid, Spain) impact on HPA axis regulation and neuroplasticity in Wistar rats. During the study, the rats were subjected to continuous unpredictable chronic mild stress and repetitively administered either a placebo, 100 mg/kg or 200 mg/kg of the saffron extract. There was also a control group not subjected to continuous unpredictable chronic mild stress but given a placebo.

Researchers found that the two groups given doses of the saffron extract saw decreases in the presence of arginine vasopressin and Corticotropin Releasing Factors (CRF) within the hypothalamus. These are two hormones that play a role in triggered the release of stress-related hormones such as adrenocorticotropic hormone (ACTH) from the pituitary gland. This in turn signals the adrenal glands to release cortisol. The group given 200 mg/ kg of the extract also experienced a significant reduction in glucocorticoid receptor (GR) expression.

“Glucocorticoid hormones, cortisol in humans and corticosterone in rodents, produced by the HPA axis and working in tandem with neuropeptides and neurotransmitters, play a pivotal role in fostering resilience, enabling the organism to handle challenges and stress,” write the researchers in the study. Prolonged stress can therefore result in excess glucocorticoid levels, which has the potential to lead to resistance to glucocorticoids at the hypothalamic glucocorticoid receptor.

“Chronic or excessive activation of the HPA axis and prolonged elevation of these hormones can contribute to the maladaptative response called allostatic overload—a state of cumulative strain wherein the body and mind get overwhelmed by constant anxiety or challenges, but don’t have the time to recover,” explained Inés Morán, PhD, scientific studies manager at Pharmactive, in a press release. “Beyond the mental overload, it can contribute to various health problems, such as metabolic diseases, and accelerate long-term wear and tear on the body’s systems.”

“Despite the growing body of research on saffron’s anti-stress properties, which includes six published studies of our proprietary, highly concentrated saffron extract, few studies have specifically investigated its role in normalizing the regulation of the HPA axis, a crucial system for stress modulation in the body,” said Carlos Rodríguez, communication manager for Pharmactive. “Through ongoing research, we are unearthing more about saffron’s benefits on cognitive well-being, and its mechanisms of action. We are realizing these extend beyond influencing serotonin expression but actually demonstrates a potential to boost resilience to occasional stress and prevent its detrimental impact on overall mental and physical health.”


Kim, C.Y.; Ko, K.; Choi, S.H.; Jo, M.; Kim, J.; Yoon, S.; Yi, I.J.; Morán-Valero, M.I.; et al. Effects of saffron extract (Affron®) with 100 mg/kg and 200 mg/kg on hypothalamic–pituitary adrenal axis and stress resilience in chronic mild stress-induced depression in wistar rats. Nutrients. 2023, 15: 4885. DOI: 10.3390/nu15234855

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