The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology
The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology
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多甲氧基黄酮 Sudachitin 调节昼夜节律时钟并改善肝脏生理机能
DOI：
10.1002/mnfr.202200270
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Chen Zheng
中科院分区：
文献类型：
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作者：
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
范围聚甲氧基黄酮（PMF）是一组天然化合物，已知显示出广泛的有益效果，以促进生理健康。最近的研究表明，生物钟是介导主要PMF Nobiletin对代谢紊乱的预防功效的重要细胞机制。Sudachitin是一种富含柑橘sudachi的PMF，其功能和作用机制知之甚少。方法和结果使用昼夜报道细胞，它表明Sudachitin调节Bmal 1启动子驱动的报道节律的昼夜幅度和周期，真实的时间qPCR分析表明，Sudachitin改变核心时钟基因的表达，特别是Bmal 1，在转录和蛋白质水平。质谱分析显示体内全身暴露。在喂食含或不含Sudachitin的高脂肪饮食的小鼠中，观察到夜间活动和白天睡眠增加，伴随着昼夜节律时间依赖性方式的显著代谢改善，包括呼吸商，血脂和葡萄糖谱以及肝脏生理学。聚焦于肝脏，RNA测序和代谢组学分析揭示了基因表达和代谢物积累的普遍昼夜变化。ConclusionThis study elucidates Sudachitin as a new clock‐modulating PMF with beneficial effects to improve dioderical metabolic homeostasis and liver physiology，提示生物钟是保障生理健康的基本机制。
ScopePolymethoxylated 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 inCitrus sudachi, and its functions and mechanism of action are poorly understood.Methods and resultsUsing circadian reporter cells, it shows that Sudachitin modulates circadian amplitude and period ofBmal1promoter‐driven reporter rhythms, and real‐time qPCR analysis shows that Sudachitin alters expression of core clock genes, notablyBmal1, 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.ConclusionThis 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.