Reveals of candidate active ingredients in Justicia and its anti-thrombotic action of mechanism based on network pharmacology approach and experimental validation

Sci Rep. 2021 Aug 25;11(1):17187. doi: 10.1038/s41598-021-96683-z.

Abstract

Thrombotic diseases seriously threaten human life. Justicia, as a common Chinese medicine, is usually used for anti-inflammatory treatment, and further studies have found that it has an inhibitory effect on platelet aggregation. Therefore, it can be inferred that Justicia can be used as a therapeutic drug for thrombosis. This work aims to reveal the pharmacological mechanism of the anti-thrombotic effect of Justicia through network pharmacology combined with wet experimental verification. During the analysis, 461 compound targets were predicted from various databases and 881 thrombus-related targets were collected. Then, herb-compound-target network and protein-protein interaction network of disease and prediction targets were constructed and cluster analysis was applied to further explore the connection between the targets. In addition, Gene Ontology (GO) and pathway (KEGG) enrichment were used to further determine the association between target proteins and diseases. Finally, the expression of hub target proteins of the core component and the anti-thrombotic effect of Justicia's core compounds were verified by experiments. In conclusion, the core bioactive components, especially justicidin D, can reduce thrombosis by regulating F2, MMP9, CXCL12, MET, RAC1, PDE5A, and ABCB1. The combination of network pharmacology and the experimental research strategies proposed in this paper provides a comprehensive method for systematically exploring the therapeutic mechanism of multi-component medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Dioxolanes / chemistry
  • Dioxolanes / pharmacology*
  • Drug Discovery / methods
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology*
  • Gene Regulatory Networks*
  • Humans
  • Justicia / chemistry
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Interaction Maps*
  • Proto-Oncogene Proteins c-met / metabolism
  • rac1 GTP-Binding Protein / metabolism

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Dioxolanes
  • Fibrinolytic Agents
  • Lignans
  • RAC1 protein, human
  • justicidins
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • rac1 GTP-Binding Protein