How brain activation induced by a sensory ingredient derived from Citrus sinensis paves the way for improved stress management

Chronic psychosocial stress represents a major challenge across many contexts, from livestock production—where it affects animal welfare and zootechnical performance—to human health. In response to this reality, industry stakeholders are seeking natural and effective solutions acting directly on the neurological mechanisms underlying stress.

Recent work carried out by the Phodé Research team in collaboration with INRAE has confirmed the effectiveness of an approach based on positive neuro-sensoriality, using a specific ingredient derived from Citrus sinensis extract. This sensory ingredient has been shown to modulate the brain’s response to stress in mammals by acting on fundamental biological pathways.

The aromatic compounds of citrus fruits help to maintain serotonergic receptor activity in the brain by acting through the olfactory and retronasal pathways, thereby contributing to modulating stress perception and supporting a natural return to homeostasis.

A multidisciplinary scientific approach

The effectiveness of the sensory ingredient is not based on simple observation, but on a rigorous three-tier scientific validation process, ranging from behavioural assessments to the analysis of gene expression within the central nervous system.

Behavioural evidence: anxiolytic-like effects in mice

Preliminary work by Coutens et al. (2020) first established the ingredient’s impact on behaviour. The sensory ingredient was tested on 132 mice subjected to pharmacologically induced stress (corticosterone administration).

One week of oral administration of the sensory ingredient demonstrated effects consistent with an anxiolytic-like action. Assessments conducted through a battery of standardised tests (including the open field test, the elevated plus maze, the novelty-suppressed feeding test for anxiety, and the tail suspension and forced swim tests for behavioural despair) showed improved behavioural outcomes. Additional findings from this study already suggested a functional interaction between the olfactory and serotonergic systems.

Coutens, B., Rekik, K., Harster, A., Etienne, P., Noirot, V., Frances, B., Guiard, B. P., 2020. A citrus-based sensory functional food ingredient induces antidepressant-like effects: possible involvement of an interplay between the olfactory and the serotonergic systems. Neuroscience 451, 149–163. https://doi.org/10.1016/j.neuroscience.2020.09.040

Brain evidence: modulation of alertness in pigs

To validate the direct impact on brain activity, a study was conducted by Menneson et al. (2020) on 20 growing female pigs subjected to a chronic psychosocial stress model (social isolation and an unpredictable environment).

Functional Magnetic Resonance Imaging (fMRI) was used to observe brain responses during an acute pharmacological stress challenge. Regular exposure to the sensory ingredient led to modulation of brain regions associated with arousal, perception, and vigilance. This modulation of brain activity in response to acute stress indicates improved stress management in animals receiving the supplementation.

Menneson, S., Serrand, Y., Janvier, R., Noirot, V., Etienne, P., Coquery, N., 2020. Regular exposure to a Citrus-based sensory functional food ingredient alleviates the BOLD brain responses to acute pharmacological stress in a pig model of psychosocial chronic stress. PLoS ONE 15, e0243893. https://doi.org/10.1371/journal.pone.0243893

Molecular evidence: activation of the serotonin receptor (5-HT1AR) in the hippocampus

To identify the precise mechanism of action, the study focused on monoamine receptor gene expression in 24 pigs subjected to the same chronic stress model for seven weeks.

Post-mortem quantitative PCR (qPCR) analyses targeted central nervous system tissues, particularly the hippocampus (involved in emotional regulation) and the prefrontal cortex (cognitive control). The study measured the expression of 5-HT1AR, 5-HT2BR and BDNF genes.

The most significant finding was a marked increase in the expression of the gene encoding the 5-HT1A receptor (Serotonin 1A receptor) in the hippocampus of pigs receiving the sensory ingredient (ING) compared with control animals (CTL) (Table 1; P < 0.05).

A citrus-based sensory feed ingredient alleviates cerebral stress responses in pigs. E.A. Arnaud, B. Guiard, D. Val-Laillet, J.-F. Gabarrou, M. Allaoua, V. Noirot. https://www.sciencedirect.com/science/article/pii/S2772283X2500946X

Conclusion

This body of work demonstrates that olfactory stimulation can be used to positively and directly modulate the brain’s response to stress, confirming the close links between the olfactory and neurochemical systems. A pioneer in the science of olfaction, Phodé reinforces its expertise in sensory actives for stress management and provides solutions with proven efficacy.

For industry stakeholders

Innovative Strategy:
This approach validates the use of natural olfactory stimulation as a direct lever for improving emotional homeostasis.

Translational relevance:
Since the pig is a physiologically relevant model and the receptor activated (5-HT1AR) is universally involved in anxiety regulation, the sensory ingredient and its mode of action open up potential applications not only for enhancing animal welfare and the sustainability of livestock systems, but also for developing functional nutritional solutions aimed at reducing psychosocial stress in other contexts, including humans.