Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract

Abstract

Anxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron®, a standardized saffron extract containing ≥3.5% of total bioactive compounds safranal and crocin isomers. Affron® was administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affron® displayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.

Saffron Extract-Induced Improvement of Depressive-Like Behavior in Mice Is Associated with Modulation of Monoaminergic Neurotransmission

“…It enables us to show here that a high dose of Safr’Inside (600 mg/Kg), which was selected based on previously published data [ 18 ], tends to improve depressive-like behavior as shown by reduced immobility index. However, it is worth mentioning that the clinical relevance of this result, as well as those obtained by other laboratories also using saffron extracts at high doses [ 18 , 19 , 46 , 48 ], is limited since they are hardly transposable to humans. Interestingly, it is not the case for the low dose (6.25 mg/Kg) tested in the present study, which was chosen based on the dose classically administered to humans (30 mg/day) using the guidelines for dose-equivalence calculation provided by the FDA [ 34 ].…”

“…However, this is unlikely since we previously achieved a similar lack of anxiety improvement following acute treatment of another set of mice with the same dose of Safr‘Inside, although using another experimental paradigm (marble burying test) (see Supplementary Figure S1 ). In addition, it is noteworthy that controversial findings regarding the potential anxiolytic effects of saffron or its active compounds have been already reported in the literature [ 14 , 21 , 48 ]. The important experimental differences among these studies (e.g., different saffron extracts, doses and routes of administration, rats versus mice, distinct strains of mice with differential stress responsivity, etc.)…”

RNA-Seq Based Transcriptome Analysis of Ethanol Extract of Saffron Protective Effect Against Corticosterone-Induced PC12 Cell Injury

“…Notably, saffron and its main components and secondary metabolites have been proved to have antioxidant [6], neuroprotective [7], and antidepressant effects [8,9], which have been preliminarily veri ed in clinical practice. The current clinical studies show that saffron has extremely low toxicity, which provides a better guarantee for the safety of long-term treatment of depression patients with saffron [10].…”

<em>Crocus sativus L.</em> Extract and Its Constituents: Chemistry, Pharmacology and Therapeutic Potential

“…In the second article, the same authors find that the anxiolytic properties of crocins are mediated by their agonistic action on the GABA A -benzodiazepine receptor [8]. Orio et al evidence the antidepressant effects of a standardized saffron extract, Affron®, suggesting that oral saffron may exert a beneficial action in anxious and depressive states [9]. The collection of the articles reporting new findings on neurological disorders is filled in nicely with a work by Maggi and colleagues, demonstrating the ability of saffron to cope with retinal neurodegeneration, and this benefi-cial action appears to be dependent on the presence of specific crocins and the contribution of other saffron components [10].…”