Pseudostellaria heterophylla polysaccharide mitigates Alzheimer's-like pathology via regulating the microbiota-gut-brain axis in 5 × FAD mice

Chuantong He; Jiahui Jiang; Junxin Liu; Longjian Zhou; Yuewei Ge; Zhiyou Yang

doi:10.1016/j.ijbiomac.2024.132372

Pseudostellaria heterophylla polysaccharide mitigates Alzheimer's-like pathology via regulating the microbiota-gut-brain axis in 5 × FAD mice

Int J Biol Macromol. 2024 May 13;270(Pt 2):132372. doi: 10.1016/j.ijbiomac.2024.132372. Online ahead of print.

Authors

Chuantong He¹, Jiahui Jiang¹, Junxin Liu¹, Longjian Zhou¹, Yuewei Ge², Zhiyou Yang³

Affiliations

¹ College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key laboratory of Marine Drugs and Nutrition for Brain Health, Zhanjiang 524088, China.
² Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China.
³ College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key laboratory of Marine Drugs and Nutrition for Brain Health, Zhanjiang 524088, China. Electronic address: zyyang@gdou.edu.cn.

PMID: 38750854
DOI: 10.1016/j.ijbiomac.2024.132372

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuroinflammation, for which gut dysbiosis may be implicated. Our previous study showed that treatment with Pseudostellaria heterophylla aqueous extract and one of its cyclopeptides, heterophyllin B, attenuate memory deficits via immunomodulation and neurite regeneration. However, whether Pseudostellaria heterophylla polysaccharide (PH-PS) exerts neuroprotective effects against AD and its underlying mechanisms remain unclear. The infrared spectrum, molecular weight, and carbohydrate composition of the PH-PS were determined. The results showed that PH-PS (Mw 8.771 kDa) was composed of glucose (57.78 %), galactose (41.52 %), and arabinose (0.70 %). PH-PS treatment ameliorated learning and spatial memory deficits, reduced amyloid β build-up, and suppressed reactive glia and astrocytes in 5 × FAD mice. 16S rRNA sequencing further showed that PH-PS remodelled the intestinal flora composition by promoting probiotic microbiota, such as Lactobacillus, Muribaculum, Monoglobus, and [Eubacterium]_siraeum_group, and suppressing inflammation-related UCG-009 and Blautia. Additionally, PH-PS restored intestinal barrier function; ameliorated peripheral inflammation by reducing the secretion of inflammatory cytokines, thereby converting M1 microglia and A1 astrocyte toward beneficial M2 and A2 phenotypes; and contributed to Aβ plaques clearance by upregulation of insulin degradation enzyme and neprilysin. Collectively, our findings demonstrate that PH-PS may prevent the progression of AD via modulation of the gut microbiota and regulation of glial polarisation, which could provide evidence to design a potential diet therapy for preventing or curing AD.

Keywords: Alzheimer's disease; Cognitive impairment; Microbiota-gut-brain axis; Pseudostellaria heterophylla polysaccharide.