Astringent flavanol fires the locus-noradrenergic system, regulating neurobehavior and autonomic nerves

Fujii, Y.; Taira, S.; Shinoda, K.; Yamato, Y.; Sakata, K.; Muta, O.; Osada, Y.; Ono, A.; Matsushita, T.; Azumi, M.; Shikano, H.; Abe, K.; Calabrese, V.; Osakabe, N.

doi:10.1101/2025.05.06.652378

bioRxiv · 10.1101/2025.05.06.652378

Astringent flavanol fires the locus-noradrenergic system, regulating neurobehavior and autonomic nerves

Fujii, Y.·Taira, S.·Shinoda, K.·Yamato, Y.·Sakata, K.·Muta, O.·Osada, Y.·Ono, A.·Matsushita, T.·Azumi, M.·Shikano, H.·Abe, K.·Calabrese, V.·Osakabe, N.

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Abstract

Astringent flavanols (FLs) have shown enhanced cognitive function in a large intervention trial, but their mechanism remains unclear due to poor bioavailability. An oral dose of FLs increased spontaneous locomotion and memory, with activation of the sympathetic-adrenergic-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axis, as shown by increased urinary catecholamine concentrations and corticotropin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of mice. MS imaging showed high intensity of noradrenaline (NA) in the locus coeruleus (LC), which plays a key role in learning and memory, the hypothalamus lateral preoptic area, which affects sleep and arousal, and the brainstem as the origin of the sympathetic nervous system, immediately after FLs administration. Subsequent in situ hybridization (ISH) analysis showed that these NAs originated from LC. Astringent compounds like FLs influence brain function and physiological changes. Furthermore, the present series of results presents novel mechanisms by which food sensory properties maintain homeostasis. Highlights- A oral dose of astringent flavanols (FLs) immediately fires locus coeruleus-noradrenaline axis - FLs enhance spontaneous locomotion and short-term memory in mice - SAM and HPA axis are also activated by an oral dose of FLs - FLs astringency affects the brain and body, contributing to homeostasis.

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Fujii, Y., Taira, S., Shinoda, K., Yamato, Y., Sakata, K., Muta, O., Osada, Y., Ono, A., Matsushita, T., Azumi, M., Shikano, H., Abe, K., Calabrese, V., Osakabe, N.. 2025-05-07. Astringent flavanol fires the locus-noradrenergic system, regulating neurobehavior and autonomic nerves. https://doi.org/10.1101/2025.05.06.652378

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