Astragalus polysaccharide ameliorates ischemic stroke via modulating the microbiota-gut-brain axis

Abstract

Ischemic stroke (IS) remains a major contributor to global disability and mortality. Astragalus polysaccharide (ASP), a naturally active component derived from Astragalus membranaceus, exhibits therapeutic potential against IS. However, their mechanism against IS via the microbiota-gut-brain axis remains unclear. Our study aimed to evaluate the mechanism of ASP against IS by middle cerebral artery occlusion (MCAO)-induced animal models combined with antibiotics (ABX) and fecal microbiota transplantation (FMT) experiments. In MCAO mice, our results showed that ASP significantly attenuated brain injury and intestinal barrier dysfunction. Transcriptomics, network pharmacology, and western blot identified LPS-TLR4-MAPK pathway as a key regulatory pathway in the regulation of IS-induced intestinal barrier dysfunction by ASP. Metagenomics and metabolomics indicated that ASP modulates SCFA-producing and anti-inflammatory bacterial genera (g_Anaerobutyricum and g_Caproiciproducens). Critically, ABX and FMT experiments confirmed that ASP’s neuroprotective effects in MCAO mice receiving gut microbiota from IS patients, with this therapeutic benefit being microbiota-dependent. Additionally, LPS levels were upregulated in clinical patients with IS. In conclusion, our findings indicated that ASP alleviates IS-induced brain injury via the microbiota-gut-brain axis.

Keywords

Ischemic stroke / Astragalus polysaccharide / Gut microbiota / LPS-TLR4-MAPK pathway / Microbiota-gut-brain axis

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82574737 and 82204973), Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (Nos. CI2026A04906, CI2024E003, CI2021A00605 and CI2021B015), the Fundamental Research Funds for the Central Public Welfare Research Institutes of Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. ZXKT25045 and ZXKT21030), the Special Program for Outstanding Young Scientific and Technological Talents (Innovation) of China Academy of Chinese Medical Sciences (No. ZZ15-YQ-034), and the Supportive Plan for Top Innovative PhD Students at China Academy of Chinese Medical Sciences.

Declaration of competing interest

These authors have no conflict of interest to declare.

Data availability

Data will be available on request by sending E-mail to the corresponding authors.

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