Deciphering the Therapeutic Mechanisms of Wuzi Ershen Decoction in Treating Oligoasthenozoospermia through the Network Pharmacology Approach

Figures

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  Figure 1. Candidate compound-candidate target (cC-cT) network of WZESD. Squares: herbs; triangles: candidate compounds for herbs of WZESD; circles: candidate targets predicted. The size of the node is proportional to the value of the degree, respectively.

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  Figure 2. Oligoasthenozoospermia-related protein interaction network. (a) Total protein-protein interaction (PPI) network for oligoasthenozoospermia. (b) 79 candidate protein targets of WZESD screened for oligoasthenozoospermia therapy. The size and color of the node are proportional to the value of betweenness and degree, respectively.

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  Figure 3. Co-bioinformatics analysis for targets of WZESD and oligoasthenozoospermia-specific proteins. (a) Circos plot for the 2 groups of proteins. Purple lines link the same proteins that are shared by multiple lists. Blue lines link different proteins where they fall into the same ontology term. (b) Enrichment network analysis for the union of the 2 groups of proteins. Each term is represented by a circle node, where its size is proportional to the number of input proteins that fall into that term, and its color represents its cluster identity. Terms with a similarity score >0.3 are linked by an edge (the thickness of the edge represents the similarity score). (c) The same enrichment network has its nodes displayed as pies. Each pie sector is proportional to the number of hits originated from the 2 lists. (d) The same enrichment network has its nodes coloured by the p value, as shown in the legend. The darker the color, the more statistically significant the node.

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  Figure 4. Potential compound-potential target (pC-pT) network of WZESD for treating oligoasthenozoospermia. The squares, triangles, and circles represent the herbs, potential compounds, and potential targets, respectively. LightSlateBlue: potential compounds and targets originated from the WZYZ pill. Red: potential compounds and targets derived from other herbs for WZESD. DeepSkyBlue: common compounds and targets in 2 comparison cohorts. The size of the node is proportional to the value of the degree.

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  Figure 5. GO and KEGG pathway analyses for the 79 target proteins via the online “Enrichr” platform (http://amp.pharm.mssm.edu/Enrichr/).

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  Figure 6. C-T network through molecular docking validation. 61 potential compounds (yellow triangles) are interacting with 21 potential targets (red circles) of WZESD. The size of the node is proportional to the value of the degree.

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  Figure 7. Predicted binding mode within the active site of the drug-target complexes obtained from AutoDock Vina. (a–c) PTGS2-1,2,5,6-tetrahydrotanshinone. (d–f) XDH-luteolin. (g–i) NOS2-hypolaetin (the PDB ID of PTGS2, XDH, and luteolin is 3NT1, 1N5X, and 3E65. (a, d, g) Global view. (b, e, h) 3D partial view. (c, f, i) 2D view for the interaction). The proteins are presented as cartoon modes, and molecules are presented as ball and stick models. Active site amino acid residues are represented as lines.