Molecular network mechanism of Shexiang Huayu Xingnao granules in treating intracerebral hemorrhage.
Ke-Qian LiuXue BaiJi-Lin ChenGuo-Jiao ChenMuhammad Ameen JamalYu-Qi HePublished in: Ibrain (2023)
We aim to explore the pharmacological efficacy and molecular network mechanism of Shexiang Huayu Xingnao granules (SX granules) in the treatment of intracerebral hemorrhage (ICH) based on experiments and network pharmacology. After the ICH model establishment, the behavioral functions of rats were assessed by the modified neurological severity score (mNSS), the wire suspension test, and the rotarod test. Brain histomorphological changes were observed using 2,3,5-triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), Nissl, and TdT-mediated dUTP nick end labeling (TUNEL) combined with neuronal nuclear (NEUN) immunofluorescence staining. The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug-disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. In conclusion, SX granules improved behavioral dysfunction, abnormal alterations in brain tissue, and cell morphology in ICH rats, and potential molecular mechanism was linked with the expression of multiple genes.
Keyphrases
- genome wide
- bioinformatics analysis
- signaling pathway
- oxidative stress
- genome wide identification
- cerebral ischemia
- poor prognosis
- resting state
- network analysis
- white matter
- pi k akt
- emergency department
- functional connectivity
- cell death
- dna methylation
- endoplasmic reticulum stress
- induced apoptosis
- epithelial mesenchymal transition
- mesenchymal stem cells
- long non coding rna
- high resolution
- risk assessment
- cell therapy
- human health