Therapeutic effects of traditional Chinese medicine compound Hua-Feng-Dan in a rat model of ischemic stroke involve renormalization of gut microbiota

ABSTRACT:

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.

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

PROVIDER: MTBLS10818 | MetaboLights | 2025-01-06

REPOSITORIES: MetaboLights