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

Pontifex, Matthew G., Connell, Emily, Le Gall, Gwenaelle ORCID: https://orcid.org/0000-0002-1379-2196, Pourtau, Line, Gaudout, David, Angeloni, Cristina, Zallocco, Lorenzo, Ronci, Maurizio, Giusti, Laura, Muller, Michael ORCID: https://orcid.org/0000-0002-5930-9905 and Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756 (2022) Saffron extract (Safr’InsideTM) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites. Food & Function, 13 (23). pp. 12219-12233. ISSN 2042-6496

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Abstract

Treatment of anxiety and depression predominantly centres around pharmacological interventions, which have faced criticism for their associated side effects, lack of efficacy and low tolerability. Saffron, which is reportedly well tolerated in humans, has been recognised for its antidepressant and anti-anxiety properties. Indeed, we previously reported upon the efficacy of saffron extract supplementation in healthy adults with subclinical anxiety. However, the molecular aetiology remains unclear. In a rodent model of low-grade chronic inflammation, we explored the impact of a saffron extract (Safr'Inside™) supplemented at a physiological dose, which equated to 22 ± 1.2 mg per day human equivalent dose for a person of 60 kg. Behavioural tests (Open Field task, Y maze, Novel object recognition), caecal 16S rRNA microbial sequencing, caecal 1H NMR metabolomic analysis and 2DE brain proteomic analyses were completed to probe gut-brain axis interactions. Time occupying the centre of the Open Field maze (OF) was increased by 62% in saffron supplemented animals. This improvement in anxiety-related behaviour coincided with gut microbial shifts, notably Akkermansia, Muribaculaceae, Christensenellacae and Alloprevotella which significantly increased in response to saffron supplementation. Akkermansia and Muribaculaceae abundance negatively correlated with the neurotoxic metabolite dimethylamine which was reduced in saffron supplemented animals. Brain proteomic analysis highlighted several significantly altered proteins including ketimine reductase mu-crystallin which also correlated with dimethylamine concentration. Both dimethylamine and ketimine reductase mu-crystallin were associated with OF performance. This may be indicative of a novel interaction across the gut-brain axis which contributes to anxiety-related disorders.

Item Type: Article
Additional Information: Funding Information: This project was funded by Activ'Inside (grant R209836) who received support for the Silver Brain Food project, a program co-financed by the “Future Investment Program” (Programme d'Investissements d'Avenir PIA3) and managed by the Investment General Secretariat and operated by Bpifrance.
Uncontrolled Keywords: carotenoids,safranal,microbiome,brain,gut-brain-axis,proteomic,metabolomic,mood,food science,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1100/1106
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 31 Oct 2022 09:30
Last Modified: 19 Apr 2023 01:16
URI: https://ueaeprints.uea.ac.uk/id/eprint/89433
DOI: 10.1039/D2FO02739A

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