The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology.
Sudachitin
circadian rhythms
hepatic physiology
multiomics
polymethoxyflavone
Journal
Molecular nutrition & food research
ISSN: 1613-4133
Titre abrégé: Mol Nutr Food Res
Pays: Germany
ID NLM: 101231818
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
13
12
2022
received:
28
04
2022
medline:
10
5
2023
pubmed:
26
2
2023
entrez:
25
2
2023
Statut:
ppublish
Résumé
Polymethoxylated flavones (PMFs) are a group of natural compounds known to display a wide array of beneficial effects to promote physiological fitness. Recent studies reveal circadian clocks as an important cellular mechanism mediating preventive efficacy of the major PMF Nobiletin against metabolic disorders. Sudachitin is a PMF enriched in Citrus sudachi, and its functions and mechanism of action are poorly understood. Using circadian reporter cells, it shows that Sudachitin modulates circadian amplitude and period of Bmal1 promoter-driven reporter rhythms, and real-time qPCR analysis shows that Sudachitin alters expression of core clock genes, notably Bmal1, at both transcript and protein levels. Mass-spec analysis reveals systemic exposure in vivo. In mice fed with high-fat diet with or without Sudachitin, it observes increased nighttime activity and daytime sleep, accompanied by significant metabolic improvements in a circadian time-dependent manner, including respiratory quotient, blood lipid and glucose profiles, and liver physiology. Focusing on liver, RNA-sequencing and metabolomic analyses reveal prevalent diurnal alteration in both gene expression and metabolite accumulation. This study elucidates Sudachitin as a new clock-modulating PMF with beneficial effects to improve diurnal metabolic homeostasis and liver physiology, suggesting the circadian clock as a fundamental mechanism to safeguard physiological well-being.
Identifiants
pubmed: 36829302
doi: 10.1002/mnfr.202200270
doi:
Substances chimiques
sudachitin
0
ARNTL Transcription Factors
0
Flavonoids
0
CLOCK Proteins
EC 2.3.1.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2200270Informations de copyright
© 2023 Wiley-VCH GmbH.
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