Angong Niuhuang Pill (
ANP) is a famous traditional Chinese
patent medicine and is used for treating ischemic or
hemorrhagic stroke for centuries. However, the mechanism of action of
ANP in
stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between
acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of
ANP in treating
acute ischemic stroke from the perspective of the gut microbiota. A mouse model of
acute ischemic stroke by
middle cerebral artery occlusion (MCAO) was established, and
16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the
sham, model, and
ANP-treated MCAO mice. The results showed that
ANP significantly ameliorated
cerebral infarct volume, improved neurological deficits, and reduced histopathological
injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover,
ANP reversed gut microbiota
dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla Bacteroidetes and Firmicutes, the families Lachnospiraceae and Prevotellaceae, and the genera Alloprevotella and Roseburia. Microbial metabolites related to
inflammation and neuroprotection, such as
prostaglandin I2 and
uridine, were also regulated by
ANP treatment.
Uridine,
guanosine, and
inosine might be potential
neuromodulators produced by the gut microbiota in the
ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter. Our results demonstrated that alleviating gut microbiota
dysbiosis is one of the mechanisms by which
ANP protects against
ischemic stroke and suggest that targeting Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-
stroke therapy.