A network pharmacology and molecular docking investigation on the mechanisms of Shanyaotianhua decoction (STT) as a therapy for psoriasis

Abstract

Psoriasis is an immune-mediated inflammatory skin disease with a complex etiology involving environmental and genetic factors. Psoriasis patients often require long-term treatment. Shanyaotianua decoction (STT), a typical traditional Chinese medicine prescription, positively affects psoriasis, although its molecular targets remain unknown. To elucidate its molecular mechanisms, a combination of network pharmacology, bioinformatics analysis, and drug similarity comparisons were employed. Participants were separated into 3 groups: non-lesional (NL), lesions after medication (LM), and psoriasis lesion groups (LS). Based on the Gene Ontology/kyoto encyclopedia of genes and genomes enrichment analyses, the key targets were mainly enriched for biological processes (immuno-inflammatory responses, leukocyte differentiation, lipid metabolic disorders, and viral infection) with the relevant pathways (Janus kinase/signal transducers and activators of transcription and adipocytokine signaling and T-helper 17 cell differentiation), thus identifying the possible action mechanism of STT against psoriasis. Target prediction for 18 STT compounds that matched the screening criteria was performed. Then, the STT compounds were intersected with the differentially expressed genes of the psoriatic process, and 5 proteins were potential targets for STT. Based on the open-source toolkit RDKit and DrugBank database, and through molecular docking and drug similarity comparisons, spinasterol, diosgenin, and 24-Methylcholest-5-enyl-3belta-O-glucopyranoside_qt may be potential drugs for psoriasis.

Figure 1.

Volcano plots and heatmaps of DEGs in NL-LS. (A) Overall distribution and number of up-and down-regulated genes. (B) Heatmap for DEGs generated by comparison in NL and LS. DEGs were detected by Wilcoxon rank sum test (q < 0.05 and log2FC > 0.3). The row represents the gene, while the column identifies the samples that are not shown in the plot. DEGs = differentially expressed genes, LS = psoriasis lesion, NL = non-lesion.

Figure 2.

GO enrichment analysis of down-/up-regulated DEGs. DEGs = differentially expressed genes, GO = gene ontology.

Figure 3.

KEGG analysis of the up-/down-regulated DEGs involved in LS. DEGs = differentially expressed genes, KEGG = Kyoto encyclopedia of genes and genomes.

Figure 4.

The chord diagram of STT and main target proteins. STT = Shanyaotianua decoction.

Figure 5.

GO and KEGG analysis of the STT target proteins. GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, STT = Shanyaotianua decoction.

Figure 6.

GSEA analysis of the STT target proteins. GSEA = gene set enrichment analysis, STT = Shanyaotianua decoction.

Figure 7.

Intersection of NL-LM-LS and STT target proteins Venn Diagram and heatmap. STT = Shanyaotianua decoction, LM = lesions after medication, LS = psoriasis lesion, NL = non-lesion.

Figure 8.

The overall interactive network diagram (herbs, active compounds, target proteins). (A) Target proteins are linked to their corresponding diseases and those diseases are linked to the corresponding disease categories they belong to. The node size and the number of the line have a direct proportional (positive) relationship with the therapeutic effect. The blue triangles represent the compounds of herbs; the yellow darts represent clinical drug targets. (B) The pink diamonds represent herbs; the blue triangles represent the compounds of herbs; the ovals represent the intersecting target proteins in treating psoriasis.

Figure 9.

Comparability of compounds and drugs from the DrugBank.

Figure 10.

Molecular docking models of putative interactions with target proteins.