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
- bioinformatics analysis
- genome wide
- signaling pathway
- cerebral ischemia
- genome wide identification
- oxidative stress
- poor prognosis
- network analysis
- white matter
- resting state
- brain injury
- epithelial mesenchymal transition
- genome wide analysis
- transcription factor
- stem cells
- functional connectivity
- bone marrow
- subarachnoid hemorrhage
- cell death
- risk assessment
- endoplasmic reticulum stress
- single molecule
- blood brain barrier
- long non coding rna
- adverse drug
- replacement therapy
- flow cytometry