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具有衰老细胞活性的根的酚类成分。

Phenolic Constituents of the Roots of with Senolytic Activity.

机构信息

Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

Department of Botany, Hanoi University of Pharmacy, Hanoi, Vietnam.

出版信息

J Nat Prod. 2020 Dec 24;83(12):3661-3670. doi: 10.1021/acs.jnatprod.0c00885. Epub 2020 Dec 1.

DOI:10.1021/acs.jnatprod.0c00885
PMID:33256407
Abstract

With the advent of senolytic agents capable of selectively removing senescent cells in old tissues, the perception of age-associated diseases has been changing from being an inevitable to a preventable phenomenon of human life. In the search for materials with senolytic activity from natural products, six new flavonostilbenes (-), three new phenylethylchromanones (-), three new phenylethylchromones (-), and four known compounds (-) were isolated from the roots of . The chemical structures of these isolated compounds were determined based on the interpretation of spectroscopic data, including 1D and 2D NMR, ECD, and HRMS. The absolute configuration of compound was also determined by a Mosher ester analysis and ECD calculations. Compounds - were shown to selectively destroy senescent cells, and the promoter activity of p16INK4A, a representative senescence marker, was reduced significantly by compound . The present results suggest the potential activity of flavonostilbene and phenylethylchromanone skeletons from . as new senolytics.

摘要

随着能够选择性清除衰老细胞的衰老细胞清除剂的出现,人们对与年龄相关的疾病的认识已经从不可避免的人类生命现象转变为可预防的现象。在从天然产物中寻找具有衰老细胞清除活性的物质的过程中,从 的根部分离得到了六个新的黄酮二苯乙烯类化合物 (-)、三个新的苯乙基色酮类化合物 (-)、三个新的苯乙基查耳酮类化合物 (-) 和四个已知化合物 (-)。这些分离化合物的化学结构是根据包括 1D 和 2D NMR、ECD 和 HRMS 在内的光谱数据解释确定的。通过 Mosher 酯分析和 ECD 计算确定了化合物 的绝对构型。化合物 - 被证明能够选择性地破坏衰老细胞,并且代表性衰老标志物 p16INK4A 的启动子活性被化合物 显著降低。这些结果表明,来自 的黄酮二苯乙烯和苯乙基色酮骨架可能具有作为新型衰老细胞清除剂的潜力。

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