Astaxanthin improve the intestinal microbiota and metabolism after ischemic stroke

As a prevalent cerebrovascular disorder, the association between ischemic stroke and gut microbiota has garnered increasing attention. Recent studies have confirmed that astaxanthin exhibits significant protective effects against ischemic stroke. However, there is still a lack of clear experimental evidence regarding whether astaxanthin can regulate the gut microbiota in patients with ischemic stroke. To investigate the neuroprotective mechanism of astaxanthin and its regulatory effect on gut microbiota, a rat stroke model was established using the middle cerebral artery occlusion method. Molecular docking and molecular dynamics were used to verify the binding stability of energy metabolism-related proteins with astaxanthin. The intervention effects of astaxanthin on ischemic brain injury were systematically evaluated through histopathological analysis (hematoxylin-eosin staining) and molecular biology assays (ELISA and Western blot). Additionally, the composition of gut microbiota was analyzed using 16 S rRNA high-throughput sequencing technology, combined with untargeted metabolomics methods, to comprehensively elucidate the regulatory effects of astaxanthin on brain metabolites, thereby clarifying its potential molecular mechanisms. Astaxanthin intervention significantly altered the structure of the gut microbiota, characterized by an increase in beneficial bacteria and a decrease in pathogenic bacteria, which concurrently led to marked changes in brain metabolites. The results of molecular docking and molecular dynamics show that astaxanthin has stable binding to the energy metabolism proteins AMPK and SIRT1. This protective mechanism not only improved the energy metabolism levels under ischemic stroke conditions but also involved the upregulation of AMPK and SIRT1 expression. The current research shows that astaxanthin may exert neuroprotective effects against ischemic stroke through the AMPK/SIRT1 signaling pathway, with its mechanism involving the regulation of gut microbiota and their metabolic products. Based on this finding, this compound holds significant research value as a potential therapeutic agent, warranting further exploration and validation.