文献类型：期刊文献

英文题名：Structural characterization of a branched α-glucan from Pseudostellaria heterophylla and its neuroprotective effect against Alzheimer's disease via regulating the microbiota-gut-brain axis

作者：Chen, Lin[1];Kang, Xiaobo[1];Deng, Wendi[1];Zhang, Yi[1];Zhao, Yuntao[1];Song, Cai[1,2,3];Yang, Zhiyou[1]

机构：[1]Guangdong Ocean Univ, Guangdong Prov Key Lab Aquat Prod Proc & Safety, Guangdong Prov Engn Lab Marine Biol Prod, Coll Food Sci & Technol,Shenzhen Inst,Zhanjiang Mu, Zhanjiang 524088, Peoples R China;[2]Dongguan 7 Peoples Hosp, Dongguan Mental Hlth Ctr, Dongguan, Peoples R China;[3]BGI Life Sci Res Inst, Neurosci Sect, Hangzhou, Peoples R China

年份：2026

卷号：374

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：SCI-EXPANDED(收录号：WOS:001820410300001)、、EI(收录号：20262721046820)、Scopus(收录号：2-s2.0-105043717555)、WOS

基金：This research was funded by Guangdong Basic and Applied Basic Research Foundation (2026A1515011666), Guangdong University Featured Innovation Program Project (2024KTSCX199), and the Sustainable Development Program of Shenzhen Science and Technology Major Program (KCXFZ20240903093925033).

语种：英文

外文关键词：Alzheimer's disease; Pseudostellaria heterophylla polysaccharide; Microbiota-gut-brain axis; Neuroprotection; Neuroinflammation

外文摘要：Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited therapeutic options. Emerging evidence highlights the gut-brain axis as a promising target, and natural polysaccharides offer multi-target advantages. Here, we isolated and structurally characterized PF30-3, a homogeneous branched alpha-D-glucan (69.91 kDa) from Pseudostellaria heterophylla, featuring a (1 -* 4)-alpha-D-glucopyranosyl backbone with (1 -* 4,6)-alpha-Dglucopyranosyl branching points. In LPS-stimulated RAW264.7 macrophages, 200 & micro;g/mL PF30-3 significantly inhibited nitric oxide release, restored cell viability, and rebalanced inflammatory cytokines. The in vivo efficacy was first validated in an A(31-42-induced zebrafish AD-like model, where 20 mg/kg PF30-3 effectively rescued spatial memory and learning impairments. These findings were further translated to 5 & times; FAD mice, in which oral administration of 50 mg/kg PF30-3 for 24 consecutive days significantly improved the recognition and spatial memory without observable acute toxicity. Mechanistically, PF30-3 reduced cerebral A(3 deposition in vivo, an effect not attributable to direct aggregation inhibition as shown by ThT and CD assays. Instead, PF30-3 exerted its effects through multiple indirect pathways, including inhibition of glial cell hyperactivation, repair of intestinal barrier integrity, rebalancing of serum inflammatory cytokines, and remodeling of gut microbiota composition, characterized by a decreased Firmicutes/Bacteroidota ratio and enrichment of beneficial genera such as Muribaculum, Bacteroides, and Prevotellaceae_UCG-001. Correlation analyses linked these microbial shifts to improved cognitive outcomes and reduced neuroinflammation. Collectively, these findings demonstrate that PF30-3 exerts neuroprotective effects through modulation of the microbiota-gut-brain axis, highlighting it as a promising natural polysaccharide-based candidate for AD therapy.