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从苦参根中分离得到的 7 个新的类甲氧基查尔酮及其抗增殖活性。

Seven new prenylated flavanones from the roots of Sophora flavescens and their anti-proliferative activities.

机构信息

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medcial University, Guizhou 550025, PR China.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.

出版信息

Bioorg Chem. 2021 Apr;109:104716. doi: 10.1016/j.bioorg.2021.104716. Epub 2021 Feb 9.

Abstract

Aiming to discover potent anti-proliferative agents from the roots of Sophora flavescens, seven new prenylated flavanones were isolated, along with 16 known compounds. Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, CD, and HRESIMS) and comparison to literature data. In the in vitro assay, 21 showed anti-proliferative activity against human hepatoma cells (HepG2). Studies of its mechanism revealed that 21 could significantly activate autophagic flux and trigger ROS release in HepG2 cells. Western blot experiments demonstrated that 21 could activate the key signaling protein of autophagy and ROS, while it does not affect the main protein of the apoptosis signaling pathway. These results suggested that 21 mediates its anti-proliferative effects through autophagic cell death, which is apoptosis-independent.

摘要

为了从苦参根部分离出具有强效抗增殖活性的物质,共分离得到了 7 个新的类异戊烯基黄酮类化合物,同时还分离得到了 16 个已知化合物。通过解析其光谱数据(1D 和 2D NMR、UV、IR、CD 和 HRESIMS)并与文献数据进行比较,确定了它们的结构。在体外实验中,化合物 21 对人肝癌细胞(HepG2)表现出抗增殖活性。对其作用机制的研究表明,化合物 21 能够显著激活自噬流并引发 HepG2 细胞中 ROS 的释放。Western blot 实验表明,化合物 21 能够激活自噬和 ROS 的关键信号蛋白,而不影响凋亡信号通路的主要蛋白。这些结果表明,化合物 21 通过非凋亡依赖性的自噬细胞死亡来介导其抗增殖作用。

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