The Pharmacological Activity of the Wenjing Decoction in Recurrent Spontaneous Abortion

Abstract

Background: Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA.

Methods: Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA (n = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software.

Results: In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF-α (tumor necrosis factor-α), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees.

Conclusion: The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.

Figure 1

The differential expression analysis of GSE121950. (a) Heatmap displayed the differentially expressed genes (DEGs). Red and green represent up- and downregulation, respectively. Orange and purple represent recurrent spontaneous abortion (RSA) and control groups, respectively. (b) Volcano plot displayed the DEGs. Red and blue dots represent up- and downregulated genes, respectively.

Figure 2

The Venn diagram of the intersected target proteins among the 933 target proteins and 1371 DEGs in GSE121950.

Figure 3

The pie chart showing the proportion of Gene Ontology (GO) terms involving the intersected target proteins.

Figure 4

The bubble diagram exhibiting the pathways for the intersected target proteins. The vertical axis represents the pathway name, while the horizontal axis shows the enrichment gene number. The larger the ratio of enriched genes to the total genes, the larger the dot size is. A brighter red dot indicates a smaller p value.

Figure 5

The protein-protein interaction (PPI) network for the intersected target proteins. The stronger the connection, the larger the dot is. Red and green represent up- and downregulation, respectively. Darker color indicates greater fold change.

Figure 6

The pharmacological network. Brown diamond, blue square, red and green circles, circles with a red border, and red hexagon represent TCMs, active ingredients, target proteins, pathway-associated target proteins, and pathways, respectively.