TY - JOUR T1 - <strong>A Network Pharmacology-Based Analysis of the Protective Mechanism of Miao Medicine Xuemaitong Capsule against Secondary Brain Damage in the Ischemic area Surrounding Intracerebral Hemorrhage</strong> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.120.000083 SP - JPET-AR-2020-000083 AU - Bo Zhang AU - Zhengyan Zeng AU - Haijun Wu Y1 - 2020/01/01 UR - http://jpet.aspetjournals.org/content/early/2020/12/11/jpet.120.000083.abstract N2 - Intracerebral hemorrhage (ICH) is a devastating disease with the high mortality. The poor outcome of ICH is partially due to combination of various secondary insults, including ischemic area. Xuemaitong capsule (XMT), a kind of traditional Chinese medicine, has been applied to clinic practice. The purpose of this study is to explore the mechanism of XMT in alleviating secondary damage in ischemic area after ICH. We screened XMT target, compound components and ICH-related targets using network pharmacology, cluster analysis, and enrichment analysis. We found that TNF signaling pathway might be the key signaling pathway for XMT treatment of ICH. ICH rat model was established, as demonstrated by poor neurological score. In the ICH rats, Western blot analysis and immunofluorescence indicated the upregulated expression of TNFR1, MAPK, NF-κB and caspase-3. Importantly, administration of XMT alleviated inflammation, edema and increased perfusion in ischemic area, while the expression of TNFR1, MAPK, NF-κB and CASP3 was decreased. Besides, Fluoro-Jade B and TUNEL staining revealed that XMT application also inhibited apoptosis and degradation of ischemic area neurons. In conclusion, these evidence elucidates that XMT alleviates neuron apoptosis, ischemic area inflammation, edema, and perfusion through TNFR1-mediated CASP3/NF-κB/MAPK axis. Significance Statement TNF is the key signaling pathway of XMT to intervention during ICH. 14 key targets (ICAM1, IL6, TNF, CCL2, PTGS2, RELA, MMP9, EDN1, MAPK1, FOS, CASP3, JUN, IL1B, MAPK8) are retrieved from the database. XMT can inhibit neuron apoptosis in the ischemic area via regulating TNFR1/CASP3. XMT alleviates inflammation and edema through regulating TNFR1/NF-κB and TNFR1/MAPK signaling pathways. XMT alleviates hypoperfusion in the cerebral ischemic area through mediating TNFR1/MAPK/EDN1. ER -