Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr’InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders

Abstract

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’InsideTM) 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.

Saffron extract (Safr'Inside™) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites

“…In addition to depression, CRYM/KR has been implicated in schizophrenia, Alzheimer's disease and amyotrophic lateral sclerosis 80 , possibly through the generation of reactive oxygen species 81 . Interestingly, we recently reported that the circulating human metabolites produced following saffron intake were able to protect human neurons against oxidative-stress-induced neurotoxicity by preserving cell viability in an ex vivo clinical model 27 .…”

“…A close/delicate relationship exists between diet and gut microbiota composition, dysfunction of which is increasingly associated with mental illnesses. Saffron, obtained from the dried stigmas of Crocus sativus 21 has been reported to have anti-anxiety and anti-depressant properties as determined by us and others in both preclinical [22][23][24] and clinical trials [25][26][27] . Regarded as safe/well-tolerated, the effectiveness of saffron in the treatment of both anxiety and depression appears comparable to that of pharmaceutical intervention.…”

“…Saffron, obtained from the dried stigmas of Crocus sativus 21 has been reported to have anti-anxiety and anti-depressant properties as determined by us and others in both preclinical 22–24 and clinical trials. 25–27 Regarded as safe/well-tolerated, the effectiveness of saffron in the treatment of both anxiety and depression appears comparable to that of pharmaceutical intervention. Despite these positive reports emphasising saffron's anti-anxiety/depressive properties, the mechanistic picture remains incomplete.…”

“…Despite these positive reports emphasising saffron's anti-anxiety/depressive properties, the mechanistic picture remains incomplete. Of the limited evidence available, saffron's anti-inflammatory properties are most frequently cited, 28 along with modulation of the monoaminergic neurotransmission 22,23 and oxidative stress, 27 indicating that these mechanisms may be an integral part of the process. Despite evidence of saffron-mediated gut microbial shift, 29,30 this has not been explored in the context of mental health/anxiety.…”

Differential malondialdehyde (MDA) detection in plasma samples of patients with major depressive disorder (MDD): A potential biomarker

“…In this context, oxidative stress (OS) is a major aetiopathological agent of MDD. 9 Most biochemical processes in biological organisms are mediated by redox reactions, in which electrons are transferred from a reducing agent to an oxidizing or oxidant agent. 10 Oxidants, also known as free radicals, are products permanently produced in the mitochondria due to cellular respiration, but they also occur in other organelles during their metabolic activities.…”