The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology
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- Kazuaki Mawatari
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
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- Nobuya Koike
- Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine 465 Kamigyo‐ku Kyoto 602‐8566 Japan
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- Kazunari Nohara
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
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- Marvin Wirianto
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
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- Takashi Uebanso
- Department of Preventive Environment and Nutrition Institute of Biomedical Sciences Tokushima University Graduate School Kuramoto‐cho 3‐18‐15 Tokushima 770‐8503 Japan
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- Takaaki Shimohata
- Department of Preventive Environment and Nutrition Institute of Biomedical Sciences Tokushima University Graduate School Kuramoto‐cho 3‐18‐15 Tokushima 770‐8503 Japan
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- Yasuhiro Shikishima
- Ikeda Yakusou Corporation 1808‐1 Shuzunakatsu, Ikeda‐cho Miyoshi‐city Tokushima 778‐0020 Japan
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- Hiroyuki Miura
- Ikeda Yakusou Corporation 1808‐1 Shuzunakatsu, Ikeda‐cho Miyoshi‐city Tokushima 778‐0020 Japan
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- Yoshitaka Nii
- Food and Biotechnology Division Tokushima Prefectural Industrial Technology Center 11‐2 Nishibari, Saika‐cho Tokushima 770‐8021 Japan
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- Mark J. Burish
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
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- Kazuhiro Yagita
- Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine 465 Kamigyo‐ku Kyoto 602‐8566 Japan
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- Akira Takahashi
- Department of Preventive Environment and Nutrition Institute of Biomedical Sciences Tokushima University Graduate School Kuramoto‐cho 3‐18‐15 Tokushima 770‐8503 Japan
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- Seung‐Hee Yoo
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
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- Zheng Chen
- Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston 6431 Fannin St. Houston TX 77030 USA
説明
<jats:sec><jats:title>Scope</jats:title><jats:p>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 <jats:italic>Citrus sudachi</jats:italic>, and its functions and mechanism of action are poorly understood.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>Using circadian reporter cells, it shows that Sudachitin modulates circadian amplitude and period of <jats:italic>Bmal1</jats:italic> promoter‐driven reporter rhythms, and real‐time qPCR analysis shows that Sudachitin alters expression of core clock genes, notably <jats:italic>Bmal1</jats:italic>, 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>
収録刊行物
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- Molecular Nutrition & Food Research
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Molecular Nutrition & Food Research 67 (9), 2023-03-17
Wiley