Depressive disorders represent a major public health concern and display a continuously rising prevalence. Importantly, a large proportion of patients develops aversive side effects and/or does not respond properly to conventional antidepressants. These issues highlight the need to identify further therapeutic strategies, including nutritional approaches using natural plant extracts with known beneficial impacts on health. In that context, growing evidence suggests that saffron could be a particularly promising candidate. This preclinical study aimed therefore to test its antidepressant-like properties in mice and to decipher the underlying mechanisms by focusing on monoaminergic neurotransmission, due to its strong implication in mood disorders. For this purpose, the behavioral and neurobiochemical impact of a saffron extract, Safr’Inside™ (6.5 mg/kg per os) was measured in naïve mice. Saffron extract reduced depressive-like behavior in the forced swim test. This behavioral improvement was associated with neurobiological modifications, particularly changes in serotonergic and dopaminergic neurotransmission, suggesting that Safr’Inside™ may share common targets with conventional pharmacological antidepressants. This study provides useful information on the therapeutic relevance of nutritional interventions with saffron extracts to improve management of mood disorders.

Increases in oxidative stress have been reported to play a central role in the vulnerability to depression, and antidepressant drugs may reduce increased oxidative stress in patients. Among the plants exerting anti-inflammatory and anti-oxidant properties, saffron, a spice derived from the flower of Crocus sativus, is also known for its positive effects on depression, potentially through its SSRI-like properties. However, the molecular mechanisms underlying these effects and their health benefits for humans are currently unclear. Using an original ex vivo clinical approach, we demonstrated for the first time that the circulating human metabolites produced following saffron intake (Safr’Inside^TM) protect human neurons from oxidative-stress-induced neurotoxicity by preserving cell viability and increasing BNDF production. In particular, the metabolites significantly stimulated both dopamine and serotonin release. In addition, the saffron’s metabolites were also able to protect serotonergic tone by inhibiting the expression of the serotonin transporter SERT and down-regulating serotonin metabolism. Altogether, these data provide new biochemical insights into the mechanisms underlying the beneficial impact of saffron on neuronal viability and activity in humans, in the context of oxidative stress related to depression.

Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including by using nutritional interventions. In that context, saffron recently received particular attention for its beneficial effects on mood, although the underlying mechanisms are poorly understood. This study investigated in mice the impact of a saffron extract (Safr’Inside™; 6.25 mg/kg, per os) on acute restraint stress (ARS)-induced depressive-like behavior and related neurobiological alterations, by focusing on hypothalamic–pituitary–adrenal axis, inflammation-related metabolic pathways, and monoaminergic systems, all known to be altered by stress and involved in depressive disorder pathophysiology. When given before stress onset, Safr’Inside administration attenuated ARS-induced depressive-like behavior in the forced swim test. Importantly, it concomitantly reversed several stress-induced monoamine dysregulations and modulated the expression of key enzymes of the kynurenine pathway, likely reducing kynurenine-related neurotoxicity. These results show that saffron pretreatment prevents the development of stress-induced depressive symptoms and improves our understanding about the underlying mechanisms, which is a central issue to validate the therapeutic relevance of nutritional interventions with saffron in depressed patients.

Acute telogen effluvium (aTE) is a transient hair loss with significant psychophysical impact. This study assessed the efficacy and safety of Hair’Inside^TM, a nutritional supplement containing green tea extract, bamboo extract, and selenium in supporting hair regrowth and improving hair quality in women with aTE. A dual in vitro and clinical approach was adopted. Human hair follicle dermal papilla cells (HFDPCs) were exposed to the investigational product, and proliferation was assessed via cell density measurements. A randomized, double-blind, placebo-controlled clinical trial was conducted in 66 female subjects with aTE, assigned to receive either the supplement or placebo for 84 days. Efficacy endpoints included phototricogram parameters (anagen/telogen hair density and ratio), hair pull test (hair shedding), brightness (gloss), and volume (expert scoring). In vitro results showed a significant increase in HFDPC proliferation following exposure to the supplement compared to the control group (+23.4%, p ≤ 0.001). In vivo, the active group demonstrated significant improvements after 42 and 84 days of supplementation in anagen hair density (+10.3 and +15.0 hair/cm²) and anagen/telogen ratio (+1.8 and +2.7), with a corresponding decrease in telogen hair density (–6.3 and -7.6 hair/cm²) that were significantly different from the placebo. At the end of the study, a significant improvement in hair shedding, brightness and volume were also observed compared to placebo. The supplement was well tolerated, with no adverse effects reported. These findings effectively support hair regrowth and improve key indicators of hair quality in women with aTE after 42 days of supplementation. The concordance between preclinical and clinical results underscores the supplement’s biological rationale and its clinical relevance.