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

May 16, 2024International journal of biological macromolecules

Pseudostellaria heterophylla polysaccharide reduces Alzheimer's-like symptoms by affecting gut bacteria and brain communication in 5×FAD mice

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Abstract

PH-PS (Mw 8.771 kDa) was composed of glucose (57.78 %), galactose (41.52 %), and arabinose (0.70 %).

PH-PS treatment improved learning and spatial memory deficits in 5 × FAD mice.
The treatment reduced amyloid β accumulation and suppressed reactive glial cells and astrocytes.
PH-PS altered the gut microbiota by increasing beneficial bacteria like Lactobacillus and reducing inflammation-related species.
The treatment restored intestinal barrier function and reduced inflammatory cytokine secretion.
PH-PS may influence microglial and astrocytic polarization towards beneficial phenotypes.
The findings suggest that PH-PS could play a role in Aβ plaque clearance.

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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.

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

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