Zhongguo Zhong Yao Za Zhi. 2026 Jul;51(13):3751-3760. doi: 10.19540/j.cnki.cjcmm.20260310.701.
ABSTRACT
This study aimed to explore the mechanism by which the ethanol extract of Cyanotis arachnoidea(ECA) ameliorates ischemic stroke(IS) in rats, based on metabolomics and transcriptomics. A rat model of middle cerebral artery occlusion(MCAO)-induced IS was established using the modified suture occlusion method. Ninety Sprague-Dawley(SD) rats were randomly divided into the sham operation(sham) group, the model(model) group, ECA low-, medium-and high-dose groups(ECA-L, ECA-M, ECA-H), and the positive drug nimodipine(NMDP) group. The therapeutic effects of ECA were evaluated by neurological deficit scores, 2,3,5-triphenyltetrazolium chloride(TTC) staining, serum biochemical assays, hematoxylin-eosin(HE) staining, and Nissl staining. Transcriptomic and metabolomic analyses were performed on brain tissues from the sham, model, and ECA-H groups. Core gene expression was verified using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The results showed that ECA significantly reduced neurological deficit scores and cerebral infarct volume, ameliorated pathological damage in the cerebral cortex, and dose-dependently downregulated the inflammatory factor levels and oxidative stress markers in IS rats. Transcriptomic analysis revealed that ECA-H regulated the expression of 328 differentially expressed genes(DEGs) in the model group, with 129 genes identified as core regulatory targets. Gene Ontology(GO) enrichment analysis showed that these DEGs were mainly involved in IS-related processes, including cerebral cortex development and neuronal development. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis showed that the DEGs were primarily enriched in pathways such as the calcium signaling pathway and the cyclic adenosine monophosphate(cAMP) signaling pathway. RT-qPCR verification demonstrated that ECA significantly upregulated the relative expression levels of 10 genes related to these two signaling pathways. Metabolomic analysis revealed that ECA-H significantly regulated the levels of 11 differential metabolites in rat brain tissues, mainly involving metabolic pathways such as folate-mediated one-carbon metabolism, lysine degradation, and cysteine and methionine metabolism. In summary, the ECA exerts neuroprotective effects in IS by synergistically activating the calcium and cAMP signaling pathways, targeting the expression of core genes, and regulating key metabolic pathways, thereby inhibiting neuroinflammation, balancing oxidative stress, and alleviating neuronal damage.
PMID:42543365 | DOI:10.19540/j.cnki.cjcmm.20260310.701