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太白贝母鳞茎中未描述的瑟瓦宁型异甾体生物碱弗里蒂泰派因A - O及其抗神经炎症和乙酰胆碱酯酶抑制活性

Frititaipaines A-O, undescribed cevanine-type isosteroidal alkaloids from the bulbs of Fritillaria taipaiensis and their anti-neuroinflammatory and AChE inhibitory activities.

作者信息

Huang Zai-Long, Qu En-Ke, Yang Lan-Run, Luo Rui, Liang Yan-Ni, Liu Shi-Jun, Xu Yuan-Zhen, Zhang Dong-Bo

机构信息

Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi, People's Republic of China.

Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi, People's Republic of China.

出版信息

Phytochemistry. 2025 Nov;239:114582. doi: 10.1016/j.phytochem.2025.114582. Epub 2025 Jun 17.

DOI:10.1016/j.phytochem.2025.114582
PMID:40553887
Abstract

Fifteen undescribed cevanine-type isosteroidal alkaloids, frititaipaines A-O (1-15), and twelve known analogs (16-27) were isolated from the bulbs of Fritillaria taipaiensis. The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic, electronic circular dichroism spectra, and single-crystal X-ray diffraction data analysis. Compounds 3, 5, and 6 displayed significant inhibitory effects against lipopolysaccharide induced NO release in BV-2 microglial cells with IC values of 6.3, 10.7, and 6.7 μM, respectively. All compounds showed no or weak acetylcholinesterase inhibitory activities as determined by the Ellman's method. Network pharmacological analysis and molecular docking results suggest that 3 may be able to treat Alzheimer's disease through pathways in cancer, PI3K-Akt signaling pathway, Rap1 signaling pathway, etc., as well as by binding PIK3CA, AKT1, SRC, PIK3R1, and ITGB1 targets.

摘要

从太白贝母鳞茎中分离得到15个未描述的瑟文碱型异甾体生物碱,即太白贝母碱A - O(1 - 15),以及12个已知类似物(16 - 27)。基于光谱、电子圆二色光谱和单晶X射线衍射数据分析,对这些之前未描述的化合物的结构,包括其绝对构型进行了全面阐释。化合物3、5和6对脂多糖诱导的BV - 2小胶质细胞中NO释放显示出显著抑制作用,IC值分别为6.3、10.7和6.7 μM。通过埃尔曼法测定,所有化合物均未显示或仅显示微弱的乙酰胆碱酯酶抑制活性。网络药理学分析和分子对接结果表明,化合物3可能能够通过癌症相关通路、PI3K - Akt信号通路、Rap1信号通路等,以及通过结合PIK3CA、AKT1、SRC、PIK3R1和ITGB1靶点来治疗阿尔茨海默病。

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