• A novel HG-type and RG-I type pectic polysaccharide was purified from Rubus caesius L. fruit. • The polysaccharide significantly ameliorated AD symptoms in zebrafish. • Its potential mechanism involves ameliorating AD via the gut-brain axis. • This study provides a reference for using zebrafish in screening neuroactive drugs. This study investigated the structural properties and therapeutic potential against Alzheimer's disease (AD) of HFP-U-1, a pectin-type polysaccharide extracted from Rubus caesius L.. Structural studies revealed that HFP-U-1 (1743 kDa) is a homogeneous pectic polysaccharide composed of homogalacturonan (HG) and rhamnogalacturonan I (RG-I) domains in a 7.2:2.5 mass ratio, and 1, 2-linked α -Rha p with C-4 branching to 1, 6-linked β -Gal p , or 1, 5-linked α-Ara f . In an AlCl₃-induced AD zebrafish model, HFP-U-1 intervention markedly improved learning and spatial memory deficits. It suppressed amyloid-beta plaque deposition, reduced oxidative stress and neuroinflammation, and lowered monoamine oxidase activity. Moreover, HFP-U-1 increased acetylcholine levels and modulated multiple AD-related pathways. Through 16S rRNA sequencing and metabolomics, HFP-U-1 was shown to reverse gut microbiota dysbiosis, elevate short-chain fatty acids (SCFAs), and restore intestinal homeostasis. These findings indicate that HFP-U-1, alleviates AD-like pathology via the gut–brain axis, demonstrating its potential as a novel therapeutic candidate for AD.
Wang et al. (Sun,) studied this question.