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诺比莱丁刺激上腺荷尔蒙,调节小鼠的日夜钟

Conn Ryan¹, Yu Tahara^1,2, Atsushi Haraguchi¹

¹Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-0056, Japan.

|May 25, 2024

概括

诺比利丁是一种类植物中的多甲基类黄,它调节了周围的生理时钟. 它的服用时间会影响时钟节奏,并通过固酶抑制影响激素分泌和基因表达.

科学领域:

时间生物学时间生物学
药理学药理学是指药理学的学科.
生物化学生物化学

背景情况:

像nobiletin这样的多甲基黄具有多样化的生物活性,包括抗氧化剂,抗炎症,抗癌和抗痴呆作用.
已知nobiletin通过与视网膜酸受体相关的孤儿受体 (ROR) α/γ调节昼夜时钟.
诺比素摄入影响昼夜时钟的最佳时间仍未确定.

研究的目的:

研究nobiletin给药对小鼠周围昼夜时钟的时间依赖性影响.
阐明一种潜在的新机制,用于nobiletin诱导的昼夜时钟调节.

主要方法:

在不同时间 (ZT4和ZT16) 给出nobiletin后,在外周器官中PER2::LUC节律的体内成像.
在注射nobiletin后测量皮质和上腺素分泌.
在外围组织中对Per1基因表达的分析.
评估诺比莱丁对固酶 (PDE) 酶的抑制作用,并与罗利普拉姆 (PDE4 抑制剂) 和SR1078 (RORα/γ 激动剂) 进行比较.

主要成果:

诺比丁的使用时间改变了周围的时钟节奏;ZT4推进了时钟,而ZT16增加了振幅.
内注射的诺比丁刺激了皮质和上腺素的分泌,并增加了Per1的表达.
诺比列丁抑制了PDE4A1A,4B1和10A2.2. 这三种类型的PDE.
诺比和罗利普拉姆,但不是SR1078,诱导了急性表达.

结论:

诺比莱丁的服用时间显著影响了周围生理时钟的功能.
诺比林调节周围的昼夜时钟,可能通过固酶抑制,影响激素分泌和基因表达.
这项研究揭示了nobiletin在外周生理时钟调节中的新功能.

关键词:

时间营养 - 时代营养昼夜节律昼夜节律功能性食品是一种功能性食品.没有公告公告周围组织的外围组织.基化酶是一种基化剂.

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