Network Pharmacology-Based Analysis on the Mechanism of Action of Ephedrae Herba-Cinnamomi Ramulus Couplet Medicines in the Treatment for Psoriasis

Abstract

BACKGROUND This study explored the mechanism of action of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) at the pharmacological level in the treatment of psoriasis. MATERIAL AND METHODS The active ingredients in MGCM were mined through literature retrieval and the BATMAN-TCM database, and potential targets were predicted. In addition, targets associated with psoriasis were acquired using multiple disease-related databases. Thereafter, an interaction network between candidate MGCM targets and the known psoriasis-associated targets was constructed based on the protein-protein interaction (PPI) data, using the STRING database. Then, the topological parameter degree was determined for mining the core targets for MGCM in the treatment of psoriasis, which also represented the major hubs within the PPI network. In addition, the core networks of targets and ingredients were constructed using Cytoscape software to apply MGCM in the treatment for psoriasis. These core targets were then analyzed for Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathway enrichment using OmicShare. RESULTS The ingredient-target core network of MGCM for treating psoriasis was constructed; it contained 52 active ingredients and corresponded to 19 core targets. In addition, based on enrichment analysis, these core targets were majorly enriched for several biological processes (immuno-inflammatory responses, leukocyte differentiation, energy metabolism, angiogenesis, and programmed cell death) together with the relevant pathways (Janus kinase-signal transducer and activator of transcription, toll-like receptors, nuclear factor kappaB, vascular endothelial growth factor, and peroxisome proliferator-activated receptor), thus identifying the possible mechanism of action of MGCM in treating psoriasis. CONCLUSIONS The present network pharmacology study indicated that MGCM alleviates various pathological factors of psoriasis through multiple compounds, multiple targets, and multiple pathways.

Figure 1

Construction of the network of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) compounds and their potential targets. The active compounds (compounds ID) collected from diverse herbal medicines were linked with corresponding potential targets to construct the compound-target network, with a node indicating an active compound (the diverse colors of circle stand for diverse herbal medicines) and the target (green square).

Figure 2

Identification of the core targets of Ephedrae Herba-Cinnamomi Ramulus couplet medicines (MGCM) in treating psoriasis. (A) The Venn diagram shows that MGCM shared 117 potential targets with known components of the pathological course related to psoriasis. (B) The protein–protein interaction (PPI) network of all 117 candidate targets of MGCM in treating psoriasis. (C) The PPI network of the core targets of MGCM in treating psoriasis.

Figure 3

(A) Construction of the core network of active ingredients of Ephedrae Herba-Cinnamomi Ramulus couplet medicines (MGCM) and their targets in treating psoriasis, and the statistical analysis of the degree of each (B) ingredient and (C) target in the network. All nodes were sorted and calculated according to the degree of freedom, and the node size in the network was associated with the degree.

Figure 4

Enrichment analysis of core targets of Ephedrae Herba-Cinnamomi Ramulus couplet medicines (MGCM) in treating psoriasis based on OmicShare. We considered a P value cutoff of ≤0.05 as significant and applied hypergeometric tests to identify (A) enriched Gene Ontology biological processes (GO-BP) and (B) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The chart shows an overview of the analysis with up to 20 significantly enriched processes and pathways.