Researchers at the China Academy of Chinese Medical Sciences and Beijing University of Chinese Medicine have uncovered new evidence that a polysaccharide derived from the traditional medicinal herb Astragalus membranaceus (Huangqi) can protect against ischemic stroke — the world’s leading cause of long-term disability — by acting through an unexpected route: the gut.

The study, published in the Chinese Journal of Natural Medicines, demonstrates that Astragalus polysaccharide (ASP) alleviates stroke-induced brain injury by modulating the “microbiota-gut-brain axis”, a two-way communication network between gut microbes and the brain that has emerged as a promising frontier in neuroscience and stroke research.

Ischemic stroke occurs when blood flow to the brain is interrupted, triggering a cascade of inflammation, neuronal death, and blood-brain barrier breakdown. Current treatments — thrombolysis, antiplatelet drugs, and mechanical thrombectomy — can restore blood flow but often fail to prevent secondary damage to distant organs, including the intestine.

Growing evidence shows that stroke rapidly disrupts gut microbial balance, elevating levels of lipopolysaccharide (LPS), an inflammatory molecule produced by Gram-negative bacteria. LPS leaks through a weakened intestinal barrier into the bloodstream, crosses into the brain, and amplifies neuroinflammation — worsening the original injury.

Using a mouse model of middle cerebral artery occlusion (MCAO), the research team led by Professor Jing Xu, Professor Shihuan Tang, and Dr. Yu Liu showed that a seven-day course of ASP significantly reduced infarct size, improved neurological scores, and preserved neurons in a dose-dependent manner. ASP also reduced markers of microglial activation — the brain’s inflammatory immune response — and restored tight junction proteins that maintain both the blood-brain barrier and the intestinal barrier.

To identify how ASP works, the researchers combined transcriptomics, network pharmacology, and molecular experiments. Their analysis converged on a single signaling cascade: LPS activating the TLR4 receptor and downstream MAPK/NF-κB pathways in the colon, driving inflammation and intestinal barrier breakdown. ASP treatment suppressed this pathway at multiple points and lowered LPS levels in the colon, serum, and brain.

Metagenomic and metabolomic analyses revealed why. ASP reshaped the stroke-disrupted gut microbiome, enriching beneficial short-chain fatty acid (SCFA)-producing and anti-inflammatory bacteria — notably Anaerobutyricum and Caproiciproducens — and restoring fecal levels of acetate, butyrate, and other SCFAs that nourish both the intestinal barrier and brain immune cells.

Two decisive experiments confirmed that ASP’s benefits are truly microbiota-dependent. When the researchers depleted gut bacteria with a broad-spectrum antibiotic cocktail, ASP completely lost its protective effects in stroke mice. Conversely, when germ-depleted mice were transplanted with fecal microbiota from human ischemic stroke patients, ASP again reduced infarct size, improved colon structure, dampened inflammation, and re-established healthy microbial communities — including the same SCFA-producing genera.

The clinical relevance was underscored by the patients themselves: serum LPS levels were significantly elevated in the 13 ischemic stroke patients enrolled in the study compared with 17 healthy participants, consistent with previous clinical reports linking high LPS to worse stroke outcomes.

The work entitled “Astragalus polysaccharide ameliorates ischemic stroke via modulating the microbiota-gut-brain axis” was published in the Chinese Journal of Natural Medicines (published on August 21, 2026).
DOI：10.1016/S1875-5364(26)61206-X