Affiliation:
1. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy Zunyi Medical University Zunyi China
2. Department of Neurology South West China Medical University Luzhou China
3. Animal Center Kunming Medical University Kunming China
4. Department of Theriogenology, Faculty of Veterinary Sciences University of Veterinary and Animal Sciences Lahore Pakistan
Abstract
AbstractWe 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.