Integrated network pharmacology, metabolomics, and microbiome studies to reveal the therapeutic effects of Anacyclus pyrethrum in PD–MCI mice

作者：Tayier Tuersong, Qian Wu, Yan Chen, Pei Li, Yu Yong, Munire Shataer, Samire Shataer, Ying Liang, Xin Yang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156729 · 被引用次数：6 · 研究领域：Herbal Medicine Research Studies、Tryptophan and brain disorders、Pharmacological Receptor Mechanisms and Effects

BACKGROUND: Anacyclus pyrethrum (l.) DC has potential value in treating Parkinson's disease (PD)-mild cognitive impairment (MCI), manifesting as impaired memory, attention, executive function, and language. However, the specific targets and modes of action of A. pyrethrum remain unclear. PURPOSE: The aim of this study was to identify the active components of A. pyrethrum and examine their effectiveness in treating a mouse model of PD-MCI. METHODS: We generated ethanol extracts of A. pyrethrum root (EEAP) and identified its active components and related targets using UHPLC-MS/MS and network pharmacology.The PD-MCI model was induced via intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). After following continuous administration of EEAP,Altered learning or memory, as well as anxiety, were tested using the morris water maze, eight-arm radial arm maze (RAM), and open-field test,elevated plus-maze. Brain histopathology and ultrastructural changes were examined using brightfield microscopy, and electron microscopy, respectively. Furthermore, protein expression was assessed using western blotting.Stool samples were used for metabolomics analysis by UHPLC-MS/MS and for 16S rDNA sequencing to determine the compositional changes of the gut microbiota.We conducted a short-chain fatty acid targeted metabolomics experiment to study their role in the gut-brain axis in PD-MCI. RESULTS: Using UPLC-MS-MS, 126 compounds were identified from A. pyrethrum sample...