基于网络药理学研究参附注射液治疗脓毒症的作用机制

doi:10.3976/j.issn.1002-4026.2022.01.004

Abstract

Abstract:

This study aimed to study the material basis of Shenfu Injection in the treatment of sepsis and its possible mechanism of action using network pharmacology and molecular docking methods. Traditional Chinese Medicine System Pharmacology Database and Analysis Platform and Swiss Target Prediction database were used to identify the potential active ingredients and drug targets of Shenfu Injection. Screening of disease targets was performed using GeneCards, OMIM, and Drugbank databases. String database and Cytoscape software were used to construct a protein-protein interaction network. Metascape platform was used for gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Cytoscape software was used to construct a component-target-pathway network. Auto Dock software was used to perform molecular docking of the key components and targets. A mouse sepsis model was developed by injecting LPS into the tail vein. The therapeutic effect of Shenfu Injection on sepsis was verified using ELISA and western blot. The results revealed 34 potential active ingredients in Shenfu Injection and 137 key targets involved in sepsis treatment. The results of GO and KEGG analyses showed that these targets primarily involved biological processes such as inflammation, apoptosis, and signal transduction and played a role in sepsis treatment through signaling pathways such as PI3K-Akt and MAPK. The results of molecular docking revealed that the key components had good binding activities with the corresponding targets. In vivo experiments verified that Shenfu Injection inhibits the expression of inflammatory factors TNF-α and IL-6 in septic mice. Western blot results showed that Shenfu Injection could significantly upregulate ERK expression (P<0.01) and downregulate p-ERK expression (P<0.01) in liver tissues. This study found that Shenfu Injection exerts its antiseptic effect through a multicomponent-multitarget-multipathway mode of action, which provides an important scientific basis for clarifying its antisepsis mechanism.

Key words: Shenfu Injection, sepsis, network pharmacology, molecular docking, in vivo experiment

CLC Number:

R285

YING Tian-hao,YU Tao,ZHAO Jia-ning,SUN Meng-meng,ZHU Xuan,LI Xiao-li,TANG Yi-di,ZHANG Lei-ming. Mechanism of Shenfu Injection in the treatment of sepsis based on network pharmacology[J].Shandong Science, 2022, 35(1): 18-27.

Figures/Tables 8

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References 33

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Mechanism of Shenfu Injection in the treatment of sepsis based on network pharmacology

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