Objective To investigate the modulatory effects of Angelica Sinensis Polysaccharide (ASP) on intestinal microbiota and its subsequent influence on cerebral ischemia/reperfusion (I/R) injury in murine models. Methods A cohort of 64 SPF level mice was stratified into four groups: sham operation group (Sham group), middle cerebral artery occlusion group (MCAO group), ASP gavage group (ASP group), and fecal microbiota transplantation group (ASP-FMT group), each comprising 16 subjects. Following a 7-day regimen of the respective interventions, the MCAO model was established. Neurological function deficits were quantified 24 hours post-MCAO using the modified Neurological Severity Scores (mNSS); cerebral infarct size was assessed via 2,3,5-triphenyltetrazolium chloride (TTC) staining; concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in the ischemic penumbra were determined using assay kits. Additionally, the expression levels of inflammatory cytokines IL-1β, IL-5, IL-6, and IL-10 in brain tissues were quantified via Western blot, while 1 the diversity of intestinal microbiota was analyzed by 6s rRNA sequencing of cecal contents. Results Compared with the MCAO group, neurological function was markedly ameliorated after ASP intervention (P<0.001), cerebral infarct size was significantly reduced (P<0.01), and oxidative stress levels were attenuated (P<0.05). Compared with the MCAO group, the expression of pro-inflammatory cytokines IL-1β, IL-5, and IL-6 were substantially decreased by ASP intervention, while concurrently upregulated the anti-inflammatory cytokine IL-10 (P<0.05). Post-MCAO, a notable depletion in the richness of intestinal microbiota and a reduction in probiotic strains were observed. However, ASP administration or fecal microbiota transplantation partially restored microbiota richness and enhanced the proportion of probiotics. A correlation was established between the modulation of intestinal microbiota and the degree of brain tissue damage. Conclusions Angelica Sinensis Polysaccharide ameliorates intestinal microbiota, mitigates oxidative stress, modulates inflammatory cytokine profiles, and thereby attenuates neurological dysfunction and reduces infarct size following cerebral ischemia/reperfusion injury.
Key words
Cerebral ischemia/reperfusion injury /
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Angelica Sinensis Polysaccharide /
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Intestinal microbiota /
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Inflammatory response
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