Polygalae Radix shortens the circadian period through activation of the CaMKII pathway.-猫眼课题宝

DOI：

10.1080/13880209.2022.2048863

发表时间：

2022-12

期刊：

Pharmaceutical biology

影响因子：

3.8

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Haraguchi A;Saito K;Tahara Y;Shibata S

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933028/

哺乳动物的生物钟系统调节生理功能。含有复方的中药和复方的中药已被用于治疗各种疾病，但很少有研究关注生物钟。我们研究了至少一种或两种坎普药材对时钟基因表达节律周期长度的缩短作用，并揭示了缩短作用的机制。我们准备了40种生药。在体外实验中，我们以PERIOD2::LUCIFERASE敲入小鼠（背景：C57BL/6J小鼠）的小鼠胚胎成纤维细胞为材料，通过蒸馏水或生药（100 μg/mL）慢性治疗（6 d），评价生药对核心时钟基因周期长度、Per2表达节律的影响。在体内实验中，我们评估了C57BL/6J小鼠分别饲喂AIN-93M或AIN-93M中添加1%生药（6周）后，在体外实验中缩短了PERIOD2::LUCIFERASE表达节律的周期长度。我们发现，在40种药材中，聚蒜子（ED50: 24.01 μg/mL）的PERIOD2::LUCIFERASE节律周期长度缩短最多，CaMKII通路参与了这一作用。此外，长期饲喂AIN-93M+复方小檗可略微缩短小鼠运动活动节律的自由奔跑期。本研究结果表明，复方白芷可能是一种治疗昼夜节律障碍的新方法，CaMKII通路可能是昼夜节律障碍的靶标通路。

The mammalian circadian clock system regulates physiological function. Crude drugs, containing Polygalae Radix, and Kampō, combining multiple crude drugs, have been used to treat various diseases, but few studies have focussed on the circadian clock. We examine effective crude drugs, which cover at least one or two of Kampō, for the shortening effects on period length of clock gene expression rhythm, and reveal the mechanism of shortening effects. We prepared 40 crude drugs. In the in vitro experiments, we used mouse embryonic fibroblasts from PERIOD2::LUCIFERASE knock-in mice (background; C57BL/6J mice) to evaluate the effect of crude drugs on the period length of core clock gene, Per2, expression rhythm by chronic treatment (six days) with distilled water or crude drugs (100 μg/mL). In the in vivo experiments, we evaluated the free-running period length of C57BL/6J mice fed AIN-93M or AIN-93M supplemented with 1% crude drug (6 weeks) that shortened the period length of the PERIOD2::LUCIFERASE expression rhythm in the in vitro experiments. We found that Polygalae Radix (ED50: 24.01 μg/mL) had the most shortened PERIOD2::LUCIFERASE rhythm period length in 40 crude drugs and that the CaMKII pathway was involved in this effect. Moreover, long-term feeding with AIN-93M+Polygalae Radix slightly shortened the free-running period of the mouse locomotor activity rhythm. Our results indicate that Polygalae Radix may be regarded as a new therapy for circadian rhythm disorder and that the CaMKII pathway may be regarded as a target pathway for circadian rhythm disorders.