Exploring the Ferroptosis Mechanism of Zhilong Huoxue Tongyu Capsule for the Treatment of Intracerebral Hemorrhage Based on Network Pharmacology and In Vivo Validation

Abstract

Objective. The purpose of this study is to explore the mechanism of the Zhilong Huoxue Tongyu (ZL) capsule in the treatment of intracerebral hemorrhage (ICH) via targeting ferroptosis based on network pharmacology. Methods. The active ingredients and related key targets of the ZL capsule were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were also performed. Finally, identified targets were validated in an in-vivo model of ICH. Results. A total of 30 active ingredients and 33 intersecting targets were identified through a TCMSP database search. Ingredients-Targets-Pathways network was constructed to filter out the key targets according to the degree value. TP53 was selected as the key target. The in-vivo validation studies demonstrated that TP53 was down-regulated and GPX4 was upregulated in rats following ZL capsule treatment. Conclusions. It is concluded that the ZL capsule could alleviate ICH in a muti-target and multi-pathway manner. ZL capsule could alleviate ICH by inhibiting ferroptosis, and TP53 is identified to be the potential target. Further research is needed to clarify the detailed anti-ferroptotic mechanism of the ZL capsule.