Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice

Camille Monchaux de Oliveira; Jennifer Morael; Alexandrine Guille; Camille Amadieu; Sylvie Vancassel; David Gaudout; Lucile Capuron; Line Pourtau; Nathalie Castanon

doi:10.3389/fnut.2023.1267839

Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice

Front Nutr. 2023 Oct 5:10:1267839. doi: 10.3389/fnut.2023.1267839. eCollection 2023.

Authors

Camille Monchaux de Oliveira^{1

2}, Jennifer Morael¹, Alexandrine Guille¹, Camille Amadieu¹, Sylvie Vancassel¹, David Gaudout², Lucile Capuron¹, Line Pourtau², Nathalie Castanon¹

Affiliations

¹ INRAE, NutriNeuro, UMR 1286, Bordeaux University, Bordeaux IPB, Bordeaux, France.
² Activ'Inside, Beychac-et-Caillau, France.

Abstract

Background: Although activation of inflammatory processes is essential to fight infections, its prolonged impact on brain function is well known to contribute to the pathophysiology of many medical conditions, including neuropsychiatric disorders. Therefore, identifying novel strategies to selectively counter the harmful effects of neuroinflammation appears as a major health concern. In that context, this study aimed to test the relevance of a nutritional intervention with saffron, a spice known for centuries for its beneficial effect on health.

Methods: For this purpose, the impact of an acute oral administration of a standardized saffron extract, which was previously shown to display neuromodulatory properties and reduce depressive-like behavior, was measured in mice challenged with lipopolysaccharide (LPS, 830 μg/kg, ip).

Results: Pretreatment with saffron extract (6.5 mg/kg, per os) did not reduce LPS-induced sickness behavior, preserving therefore this adaptive behavioral response essential for host defense. However, it interfered with delayed changes of expression of cytokines, chemokines and markers of microglial activation measured 24 h post-LPS treatment in key brain areas for behavior and mood control (frontal cortex, hippocampus, striatum). Importantly, this pretreatment also counteracted by that time the impact of LPS on several neurobiological processes contributing to inflammation-induced emotional alterations, in particular the activation of the kynurenine pathway, assessed through the expression of its main enzymes, as well as concomitant impairment of serotonergic and dopaminergic neurotransmission.

Conclusion: Altogether, this study provides important clues on how saffron extract interferes with brain function in conditions of immune stimulation and supports the relevance of saffron-based nutritional interventions to improve the management of inflammation-related comorbidities.

Keywords: dopaminergic neurotransmission; kynurenine pathway; lipopolysaccharide; neuroinflammation; nutritional interventions; saffron extract; serotonergic neurotransmission; sickness behavior.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Institut National de la Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Association Nationale de la Recherche et de la Technologie (ANRT: 2018/0592); French National Research Agency (ANR: ANR-18-PRIM-0016-06) as part of the Partnership for Research and Innovation in the Mediterranean Area (PRIMA) program; the Marcel Dassault Prize for Research in Mental Disorders (Fondation FondaMental) and Activ’Inside (2200121–2494). CMdO was the recipient of a doctoral fellowship from the ANRT (2018/0592). CA was funded by ANR (ANR-18-PRIM-0016–06).