Abstract
Background. Banxia Baizhu Tianma Decoction (BBTD) is a traditional Chinese medicine (TCM) and has been revealed to promote symptoms of preeclampsia (PE) in clinical practice. However, its mechanisms of action and molecular targets for the treatment of PE are not clear. Method. The potential mechanisms of the BBTD against PE were explored using network pharmacology approach and bioinformatic analysis. The PE animal model was induced by phosphatidylserine/dioleoyl-phosphatidylcholine. The effects of BBTD in the treatment of PE were evaluated in vitro and in vivo. The expressions of RNA and proteins were measured by quantitative real-time polymerase chain reaction and western blotting, respectively. The cell behavior was detected using the MMT assay, Transwell assay, and flow cytometry assay. Results. A total of 173 active compounds of BBTD with 346 targets were identified, and 516 target genes related to PE were also identified from databases. 195 candidate targets for BBTD were screened from the merged PPI network of BBTD-target proteins and PE-related targets. The pathway enrichment analyses showed that the BBTD had the potential to influence a variety of biological pathways. Further pathway-gene network analysis suggested BBTD may improve symptoms of PE via several genes, including MDM2, TP53, RELA, MYC, AKT1, and EGFR. The validation results demonstrated that BBTD treatment promoted pregnancy outcome in the PE animal model. Meanwhile, BBTD regulated the gene expression of MDM2, TP53, RELA, MYC, and EGFR and inhibited the EGFR-JAK/STAT signaling pathway in placental tissue and trophoblast cells. In addition, BBTD promoted the proliferation and invasion and reduced the apoptosis of trophoblast cells. Conclusion. BBTD improved PE by inhibiting the EGFR-JAK/STAT signaling pathway and promoting the proliferation and invasion and reduced the apoptosis of trophoblast cells.
Highlights
Preeclampsia (PE) is a serious pregnancy-related disorder and one of the main causes of maternal and fetal morbidity and mortality worldwide [1]
To further investigate the core genes involved in the anti-PE effect of Banxia Baizhu Tianma Decoction (BBTD), the significantly enriched pathways and the related genes were obtained to construct the genepathway network, as shown in Figure 6. e topological analysis of the 28 pathways and 136 genes was carried out with betweenness centrality (BC), and the results suggested that RPS6 had the most
Our results showed that the number of the invasive trophoblast cells was decreased in the PE group compared with that in the control group, whereas BBTD treatment significantly increased the number of the invasive trophoblast cells (Figures 8(c) and 8(d))
Summary
Preeclampsia (PE) is a serious pregnancy-related disorder and one of the main causes of maternal and fetal morbidity and mortality worldwide [1]. It is characterized by proteinuria, hypertension, unexplained seizure, and severe headache [2]. E validation results demonstrated that BBTD treatment promoted pregnancy outcome in the PE animal model. BBTD regulated the gene expression of MDM2, TP53, RELA, MYC, and EGFR and inhibited the EGFR-JAK/STAT signaling pathway in placental tissue and trophoblast cells. BBTD improved PE by inhibiting the EGFR-JAK/STAT signaling pathway and promoting the proliferation and invasion and reduced the apoptosis of trophoblast cells
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