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Astaxanthin improve the intestinal flora and metabolism after ischemic stroke

ABSTRACT:

Abstract:

Background and Objective. 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 microbiome in patients with ischemic stroke.

Methods. 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 16S 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.

Results. 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.

Conclusions. Research indicates 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13080 | MetaboLights | 2025-10-15

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13080_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13080_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13080_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13080_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:<p>Hua-Feng-Dan is a traditional Chinese medicine compound used to treat ischemic stroke, but little is known about its therapeutic mechanism. This study explored whether and how the mechanism involves readjustment of gut microbiota. Rats were subjected to middle cerebral artery occlusion as a model of ischemic stroke or to sham surgery, then treated or not with Hua-Feng-Dan. The different groups of animals were compared in terms of neurological score, cerebral infarct volume and brain histopathology to assess stroke severity. They were also compared in terms of indices of intestinal barrier permeability, inflammation and oxidative stress as well as composition of the gut microbiota and their metabolites. Hua-Feng-Dan significantly reduced cerebral infarct volume and improved neurological score and brain histopathology on the ischemic side of the brain. It partially reversed stroke-induced intestinal leakiness, inflammation, dyslipidemia and oxidative stress, as well as the stroke-induced increase in pathogenic gut microbiota (e.g. Escherichia-Shigella, Enterococcus, Clostridium_innocuum_group) and decrease in beneficial microbiota (e.g. Lachnospiraceae, unclassified__f__Lachnospiracea and Ruminococcus_torques_group). The treatment altered levels of 39 metabolites produced during metabolism mainly of amino acids, short-chain fatty acids and essential fatty acids. Levels of factors related to inflammation and intestinal barrier permeability correlated positively with relative abundance of Escherichia-Shigella and Clostridium_innocuum_group, and negatively with 4-(glutamylamino)butanoate, 2-hydroxy-3-methylbutyric acid, dihomo-alpha-linolenic acid, dihomolinoleic acid and 10-nitrolinoleic acid. Conversely, levels of 4-(glutamylamino)butanoate, 2-hydroxy-3-methylbutyric acid and 10-nitrolinoleic acid correlated positively with relative abundance of unclassified__f__Lachnospiracea. Our results suggest that Hua-Feng-Dan may mitigate ischemic stroke injury by renormalizing gut microbiota and restoring gut barrier function and gut metabolism, thereby helping to alleviate inflammatory and neurological damage.</p>

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Astaxanthin improve the intestinal flora and metabolism after ischemic stroke

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