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

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

doi:10.1016/j.phytochem.2025.114582

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

Phytochemistry. 2025 Jun 17:114582. doi: 10.1016/j.phytochem.2025.114582. Online ahead of print.

Authors

Zai-Long Huang¹, En-Ke Qu¹, Lan-Run Yang¹, Rui Luo¹, Yan-Ni Liang¹, Shi-Jun Liu², Yuan-Zhen Xu³, Dong-Bo Zhang⁴

Affiliations

¹ 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.
² 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. Electronic address: 1501002@sntcm.edu.cn.
³ Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, People's Republic of China. Electronic address: yzxu@nwafu.edu.cn.
⁴ 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. Electronic address: symensu@163.com.

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

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 IC₅₀ 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.

Keywords: AChE; Fritillaria taipaiensis; Liliaceae; anti-neuroinflammatory activity; isosteroidal alkaloids; molecular docking; network pharmacological analysis.