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The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology.
Mawatari, Kazuaki; Koike, Nobuya; Nohara, Kazunari; Wirianto, Marvin; Uebanso, Takashi; Shimohata, Takaaki; Shikishima, Yasuhiro; Miura, Hiroyuki; Nii, Yoshitaka; Burish, Mark J; Yagita, Kazuhiro; Takahashi, Akira; Yoo, Seung-Hee; Chen, Zheng.
Afiliação
  • Mawatari K; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA.
  • Koike N; Department of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
  • Nohara K; Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, 465 Kamigyo-ku, Kyoto, 602-8566, Japan.
  • Wirianto M; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA.
  • Uebanso T; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA.
  • Shimohata T; Department of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
  • Shikishima Y; Department of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
  • Miura H; Ikeda Yakusou Corporation, 1808-1 Shuzunakatsu, Ikeda-cho, Miyoshi-city, Tokushima, 778-0020, Japan.
  • Nii Y; Ikeda Yakusou Corporation, 1808-1 Shuzunakatsu, Ikeda-cho, Miyoshi-city, Tokushima, 778-0020, Japan.
  • Burish MJ; Food and Biotechnology Division, Tokushima Prefectural Industrial Technology Center, 11-2 Nishibari, Saika-cho, Tokushima, 770-8021, Japan.
  • Yagita K; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA.
  • Takahashi A; Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, 465 Kamigyo-ku, Kyoto, 602-8566, Japan.
  • Yoo SH; Department of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
  • Chen Z; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA.
Mol Nutr Food Res ; 67(9): e2200270, 2023 05.
Article em En | MEDLINE | ID: mdl-36829302
ABSTRACT
SCOPE 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. METHODS AND

RESULTS:

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.

CONCLUSION:

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Relógios Circadianos Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Relógios Circadianos Idioma: En Ano de publicação: 2023 Tipo de documento: Article