Hydroxy-β-sanshool isolated from Zanthoxylum piperitum (Japanese pepper) shortens the period of the circadian clock
Hydroxy-β-sanshool isolated from Zanthoxylum piperitum (Japanese pepper) shortens the period of the circadian clock
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DOI：
10.1039/d2fo01036d
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发表时间：
2022-08-09
期刊：
影响因子：
6.1
通讯作者：
Miyazaki，Koyomi
中科院分区：
文献类型：
--
作者：
Tomita，Tatsunosuke;Kawano，Yasuhiro;Miyazaki，Koyomi
我们发现，花椒的乙醇提取物可以缩短细胞水平的昼夜节律，这种活性是由于羟基-β-山椒醇，在这种植物的次生代谢产物。采用乙醇提取法对Z.使用固相萃取和反相HPLC反复分级分离胡椒，然后使用实时报告基因测定监测加载了级分的细胞的昼夜节律。对其中一个色谱峰进行了纯化，并利用液相色谱-精密度-质谱联用技术鉴定其为羟基-β-山椒醇。该化合物在细胞水平上缩短了Bmal 1和Per 2的周期。用羟基-β-山椒醇孵育细胞24 h导致Per 2启动子活性上调。羟基-β-山椒醇还剂量依赖性地上调生物钟基因Bmal 1、Per 1、Per 2和Cry 1以及生物钟控制的氧化应激反应基因Gpx 1和Sod 2的表达。
We showed that an ethanol extract from Zanthoxylum piperitum can shorten the circadian rhythm at the cellular level and that this activity was due to hydroxy-β-sanshool, a secondary metabolite in this plant. An ethanol extract of Z. piperitum was repeatedly fractionated using solid phase extraction and reverse-phase HPLC, then the circadian rhythms of cells to which the fractions were loaded were monitored using real-time reporter gene assays. We purified one HPLC peak and identified it as hydroxy-β-sanshool using liquid chromatography (LC)-precision-mass spectrometry (MS). This compound shortened the period of Bmal1 and Per2 at the cellular level. Incubation cells for 24 h with hydroxy-β-sanshool resulted in upregulated Per2 promoter activity. Hydroxy-β-sanshool also dose-dependently upregulated expression of the clock genes Bmal1, Per1, Per2 and Cry1 and the clock-controlled oxidative stress responsive genes Gpx1and Sod2.