Screening Safflower Injection for Constituents with Activity against Stroke Using Comprehensive Chemical Profiling Coupled with Network Pharmacology

Objective: This study aimed to explore safflower injection (SI) for constituents with activity against ischemic stroke using a combination of chemical analysis and a network pharmacology strategy. Materials and Methods: The main ingredients of SI were comprehensively identified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, and the core targets and pathways associated with stroke were predicted using PharmMapper and Kyoto Encyclopedia of Genes and Genomes analysis. Cytoscape software was used to visualize and analyze the active compound-target-pathway network of SI regulating ischemic stroke. Results: A total of 76 chemical compounds were identified from the SI sample, including 63, which regulated 88 targets that were ultimately enriched in 12 key ischemia stroke-related signaling pathways. Kaempferol-3-O-sophoroside, kaempferol-3-O-rutinoside, carthamoside B6, neoeriocitrin, and 6-hydroxykaempferol-3-O-rutinoside-6-O-glucoside were determined to be important for stroke treatment because they had a higher degree value in the network than other constituents did. Moreover, the characteristic components isolated from SI showed protective effect mainly by acting on multiple targets including AKT1, epidermal growth factor receptor, transforming growth factor-beta receptor (TGFBR), Ras homolog, mTORC1 binding, caspase 3, and glycogen synthase kinase 3 beta, which were involved in different signaling pathways including phosphoinositide 3-kinase-Akt, mitogen-activated protein kinase, neurotrophin, ErbB, mechanistic target of rapamycin, and tumor necrosis factor. Conclusions: This study proposed a network pharmacology and chemical component profiling strategy for the systematic understanding of the therapeutic material basis of using SI against ischemic stroke.

Automated summary

This study identified 76 chemical compounds in SI, which regulated 88 core targets associated with ischemic stroke and enriched in 12 key signaling pathways. Certain components in SI were determined to be crucial for stroke treatment due to their higher degree value in the network. The characteristic components from SI exhibited protective effects mainly by acting on multiple targets involved in various signaling pathways.