Abstract
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.
Highlights
Mood disorders are one of the most prevalent psychiatric disorders and currently represent a leading cause of disability worldwide [1]
We focused on genes coding for 5-HT receptors (5-Htr1a: Mm00434106_s1 and 5-Htr1b: Mm00439377_s1) and the 5-HT transporter (SERT: Mm00439391_m1) for 5-HT pathway, DA receptors (DRD1: Mm01353211_m1 and DRD2: Mm00438545_m1), the enzyme Catechol-O-Methyltransferase (COMT: Mm00514377_m1) and the DA transporter (DAT: Mm00438388_m1) for DA pathway, and the monoamine oxidases (Maoa: Mm00558004_m1 and Maob: Mm00555412_m1) that catabolize both 5-HT and DA
In order to define a behaviorally effective dose of Safr’Inside to use in the experiment, we compared the impact of a low dose (6.25 mg/Kg) and a high dose (600 mg/Kg) on depressive-like behavior, as assessed in the forced swim test (FST), a classical rodent test of depression [37]
Summary
Mood disorders are one of the most prevalent psychiatric disorders and currently represent a leading cause of disability worldwide [1]. Important side effects that are directly linked to these pharmacological treatments often occur, limiting in turn the increasing dosage regimen classically recommended to optimize therapeutic response [4,5] These issues promote heightened interest in identifying new strategies relevant to manage depressive symptoms in the largest proportion of patients, while reducing side effects. This historic spice, renowned for its culinary properties, has been used for centuries for its positive impact on health [10] It contains a large number of biologically active compounds, the four main ones being crocin and crocetin, two carotenoid pigments responsible for its color; picrocrocin, which provides its flavor and bitter taste; and safranal, a volatile compound responsible for its aroma and smell. Answering this question seems essential to better understand the therapeutic effect of nutritional interventions with saffron
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