Multi-omics analysis of untargeted metabolomics and gut microbiota study on the mechanism of Astragalus-Safflower to coordinate the regulation of energy metabolism pathways and gut microbiota remodeling to improve ischemic stroke.
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Abstract
Ischemic stroke (IS) is a detrimental neurological disorder with limited clinical therapeutic options. The Astragalus-Safflower herb pair (AS) shows therapeutic effects against IS, but its mechanism remains unclear. Herein, this study combined cerebral untargeted metabolomics, mitochondrial ultrastructural observation and 16 S rDNA gut microbiota profiling to systematically explore its neuroprotective mechanism. This study aimed to evaluate the efficacy of AS in alleviating IS, and investigate its mechanism of action. Rat models of middle cerebral artery occlusion (MCAO) were established using the intraluminal filament method. Behavioral tests confirmed that AS significantly improved neurological deficits and motor function. Untargeted metabolomics revealed that AS reversed nine IS-related energy metabolites in brain tissue. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated involvement of nicotinamide metabolism and the TCA cycle. Molecular studies demonstrated that AS regulated mitochondrial energy metabolism via the AMPK/Sirt1/PGC-1α axis. Additionally, 16 S rDNA sequencing showed that AS restructured gut microbiota composition. Correlation analysis suggested a gut-brain axis mechanism linking microbial changes to cerebral energy metabolism. In conclusion, AS exerts neuroprotection against IS by activating the AMPK/Sirt1/PGC-1α pathway, thereby enhancing TCA cycle activity and maintaining energy homeostasis. Concurrently, AS reshapes the gut microbiota, contributing to its effects via the gut-brain axis. Taken together, this integrated multi-omics study systematically clarifies the multi-target pharmacological characteristics of AS. These findings provide a novel multi-target mechanistic basis for the clinical application of AS in the treatment of IS and enrich the understanding of its synergistic neuroprotective mechanism.
期刊介绍：
Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.
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