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Published on: December 9, 2018
Astragalus polysaccharide ameliorates ischemic stroke via modulating the microbiota-gut-brain axis
Yu Li1, Jing Zhang1, Shuo Li2
1State Key Laboratory for Quality Essurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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.
Insights
Astragalus polysaccharide (ASP) shows promise in treating ischemic stroke (IS) by protecting the brain and gut barrier. Its therapeutic effects are dependent on gut microbiota modulation, highlighting the microbiota-gut-brain axis.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Ischemic stroke (IS) is a leading cause of global disability and mortality.
- Astragalus polysaccharide (ASP), derived from Astragalus membranaceus, has shown therapeutic potential for IS.
- The precise mechanism of ASP's action, particularly through the microbiota-gut-brain axis, remains largely unexplored.
Purpose of the Study:
- To elucidate the mechanism by which ASP exerts neuroprotective effects against IS.
- To investigate the role of the gut microbiota in mediating ASP's therapeutic benefits in IS.
Main Methods:
- Middle cerebral artery occlusion (MCAO) mouse models were employed.
- Experiments included antibiotic treatment (ABX) and fecal microbiota transplantation (FMT).
- Transcriptomics, network pharmacology, western blot, metagenomics, and metabolomics were utilized.
Main Results:
- ASP significantly reduced brain injury and intestinal barrier dysfunction in MCAO mice.
- The LPS-TLR4-MAPK pathway was identified as a key regulatory pathway.
- ASP modulated gut microbiota, increasing beneficial SCFA-producing bacteria like g_Anaerobutyricum and g_Caproiciproducens.
- Neuroprotection by ASP was confirmed to be microbiota-dependent.
Conclusions:
- ASP alleviates IS-induced brain injury through the microbiota-gut-brain axis.
- The findings highlight the therapeutic potential of ASP for IS, emphasizing the gut microbiota's crucial role.
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