Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The preventive effects of aspirin on preeclampsia based on network pharmacology and bioinformatics



This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein–protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C–X–C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing preeclampsia.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Venn diagram of preeclampsia and aspirin targets.
Fig. 2: Top 20 biological processes and KEGG signaling pathways of the intersecting targets.
Fig. 3: Protein–protein interaction network and hub targets.
Fig. 4: Molecular docking of aspirin and proteins.


  1. Bearblock E, Aiken CE, Burton GJ. Air pollution and pre-eclampsia; associations and potential mechanisms. Placenta. 2020;104:188–94.

    Article  Google Scholar 

  2. ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol 2018;132:e44–52.

  3. Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin. Am J Obstet Gynecol. 2020; e-pub ahead of print 21 August 2020;

  4. Su MT, Wang CY, Tsai PY, Chen TY, Tsai HL, Kuo PL. Aspirin enhances trophoblast invasion and represses soluble fms-like tyrosine kinase 1 production: a putative mechanism for preventing preeclampsia. J Hypertens. 2019;37:2461–9.

    CAS  Article  Google Scholar 

  5. Xu B, Shanmugalingam R, Chau K, Pears S, Hennessy A, Makris A. The effect of acetyl salicylic acid (Aspirin) on trophoblast-endothelial interaction in vitro. J Reprod Immunol. 2017;124:54–61.

    CAS  Article  Google Scholar 

  6. Sun J, Zhang H, Liu F, Tang D, Lu X. Ameliorative effects of aspirin against lipopolysaccharide-induced preeclampsia-like symptoms in rats by inhibiting the pro-inflammatory pathway. Can J Physiol Pharm. 2018;96:1084–91.

    CAS  Article  Google Scholar 

  7. Zhang X, Gao R, Zhou Z, Tang X, Lin J, Wang L, et al. A network pharmacology based approach for predicting active ingredients and potential mechanism of Lianhuaqingwen capsule in treating COVID-19. Int J Med Sci. 2021;18:1866–76.

    CAS  Article  Google Scholar 

  8. Lin L, Li G, Zhang W, Wang YL, Yang H. Low-dose aspirin reduces hypoxia-induced sFlt1 release via the JNK/AP-1 pathway in human trophoblast and endothelial cells. J Cell Physiol. 2019;234:18928–41.

    CAS  Article  Google Scholar 

  9. Khanabdali R, Shakouri-Motlagh A, Wilkinson S, Murthi P, Georgiou HM, Brennecke SP, et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med. 2018;96:1215–25.

    CAS  Article  Google Scholar 

  10. Li Y, Zhou C, Lei W, Wang K, Zheng J. Roles of aryl hydrocarbon receptor in endothelial angiogenic responsesdagger. Biol Reprod. 2020;103:927–37.

    Article  Google Scholar 

  11. Slonchak AM, Martseniuk OP, Rzeszowska-Wolny J, Vidlak P, Obolens’ka M. [Some aspects of glutathione S-transferase P1-1 gene transcription regulation in human placenta]. Ukr Biokhim Zh 1999;2007;79:67–75.

    CAS  Google Scholar 

  12. Huang Q, Hu B, Han X, Yang J, Di X, Bao J, et al. Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model. Hypertension Res. 2020;43:263–70.

    CAS  Article  Google Scholar 

  13. Huai J, Li GL, Lin L, Ma JM, Yang HX. Phosphoproteomics reveals the apoptotic regulation of aspirin in the placenta of preeclampsia-like mice. Am J Transl Res. 2020;12:3361–3375.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Panagodage S, Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP, et al. Low-dose acetylsalicylic acid treatment modulates the production of cytokines and improves trophoblast function in an in vitro model of early-onset preeclampsia. Am J Pathol. 2016;186:3217–3224.

    CAS  Article  Google Scholar 

  15. Pai CH, Yen CT, Chen CP, Yu IS, Lin SW, Lin SR. Lack of thromboxane synthase prevents hypertension and fetal growth restriction after high salt treatment during pregnancy. PloS One. 2016;11:e0151617.

    Article  Google Scholar 

  16. Sheridan R, Belludi C, Khoury J, Stanek J, Handwerger S. FOXO1 expression in villous trophoblast of preeclampsia and fetal growth restriction placentas. Histol Histopathol. 2015;30:213–22.

    PubMed  Google Scholar 

  17. Al-Far HFM, Tjessem IH, Fuglsang J, Lauszus FF. Preeclampsia is associated with increased ambulatory arterial stiffness index in type 1 diabetes mellitus. Eur J Obstet, Gynecol, Reprod Biol. 2017;216:153–8.

    Article  Google Scholar 

  18. Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low-dose aspirin for prevention of complications in pregnancy. Chronobiol Int. 2013;30:260–79.

    CAS  Article  Google Scholar 

  19. Gairard A, Lopez-Miranda V, Pernot F, Beck JF, Coumaros G, Van Overloop B, et al. Effect of i1 imidazoline receptor agonist, moxonidine, in nitric oxide-deficient hypertension in pregnant rats. J Cardiovascular Pharmacol. 2004;43:731–736.

    CAS  Article  Google Scholar 

  20. Plenty NL, Faulkner JL, Cotton J, Spencer SK, Wallace K, LaMarca B, et al. Arachidonic acid metabolites of CYP4A and CYP4F are altered in women with preeclampsia. Prostaglandins Other Lipid Mediat. 2018;136:15–22.

    CAS  Article  Google Scholar 

  21. Mistry HD, Kurlak LO, Mansour YT, Zurkinden L, Mohaupt MG, Escher G. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia. J Lipid Res. 2017;58:1186–95.

    CAS  Article  Google Scholar 

  22. Herse F, LaMarca BB, Hubel CA, Laivuori H, Huppertz B, Verlohren S, et al. OS066. Intrauterine CYP2J2 expression and circulating epoxyeicosatrienoic acid levels in preeclampsia. Pregnancy Hypertens. 2012;2:212–3.

    CAS  Article  Google Scholar 

  23. Harati-Sadegh M, Kohan L, Teimoori B, Mehrabani M, Salimi S. Analysis of polymorphisms, promoter methylation, and mRNA expression profile of maternal and placental P53 and P21 genes in preeclamptic and normotensive pregnant women. J Biomed Sci. 2019;26:92.

    Article  Google Scholar 

  24. Jiang R, Wang T, Zhou F, Yao Y, He J, Xu D. Bioinformatics-based identification of miRNA-, lncRNA-, and mRNA-associated ceRNA networks and potential biomarkers for preeclampsia. Medicine. 2020;99:e22985.

    CAS  Article  Google Scholar 

  25. Moon KC, Park JS, Norwitz ER, Kim DI, Oh KJ, Park CW, et al. Expression of extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinase in the invasive trophoblasts at the human placental bed. Placenta. 2008;29:391–5.

    CAS  Article  Google Scholar 

  26. Su YF, Yang SH, Lee YH, Wu BC, Huang SC, Liu CM, et al. Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway. Eur J Pharmacol. 2014;738:101–10.

    CAS  Article  Google Scholar 

  27. Li FH, Han N, Wang Y, Xu Q. Gadd45a knockdown alleviates oxidative stress through suppressing the p38 MAPK signaling pathway in the pathogenesis of preeclampsia. Placenta. 2018;65:20–28.

    CAS  Article  Google Scholar 

  28. Fan M, Li X, Gao X, Dong L, Xin G, Chen L, et al. LPS induces preeclampsia-like phenotype in rats and HTR8/SVneo cells dysfunction through TLR4/p38 MAPK pathway. Front Physiol. 2019;10:1030.

    Article  Google Scholar 

  29. Castro P, Nasser H, Abrahao A, Dos Reis LC, Rica I, Valenca SS, et al. Aspirin and indomethacin reduce lung inflammation of mice exposed to cigarette smoke. Biochemical Pharmacol. 2009;77:1029–39.

    CAS  Article  Google Scholar 

  30. Hastie R, Brownfoot FC, Pritchard N, Hannan NJ, Cannon P, Nguyen V, et al. EGFR (Epidermal growth factor receptor) signaling and the mitochondria regulate sFlt-1 (soluble FMS-like tyrosine kinase-1) secretion. Hypertension. 2019;73:659–70.

    CAS  Article  Google Scholar 

  31. Bashir AIJ, Kankipati CS, Jones S, Newman RM, Safrany ST, Perry CJ, et al. A novel mechanism for the anticancer activity of aspirin and salicylates. Int J Oncol. 2019;54:1256–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Lan KC, Lai YJ, Cheng HH, Tsai NC, Su YT, Tsai CC, et al. Levels of sex steroid hormones and their receptors in women with preeclampsia. Reprod Biol Endocrinol. 2020;18:12.

    CAS  Article  Google Scholar 

  33. Goksu Erol AY, Nazli M, Yildiz SE. Expression levels of cyclooxygenase-2, tumor necrosis factor-alpha and inducible NO synthase in placental tissue of normal and preeclamptic pregnancies. J Matern Fetal Neonatal Med. 2012;25:826–30.

    CAS  Article  Google Scholar 

  34. Reijnders D, Liu CC, Xu X, Zhao AM, Olson KN, Butler SD, et al. Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia. Physiol Genom. 2018;50:385–92.

    CAS  Article  Google Scholar 

  35. Altinoz MA, Korkmaz R. NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma. 2004;51:239–47.

    CAS  PubMed  Google Scholar 

Download references


This work was supported by National Natural Science Foundation of China (No. 81903696 to Jiejie Zhang; No. 81974236 to Weishe Zhang) and Postdoctoral Foundation of Xiangya Hospital Central South University (No. 2209090555067 to Jiejie Zhang).

Author information

Authors and Affiliations



Jiejie Zhang and Jingrui Huang analyzed the data. Jiejie Zhang drafted the paper. Yanhua Zhao and Weishe Zhang were responsible for design and co-ordination of the project and preparation of the manuscript. All authors reviewed and approved submission of the manuscript.

Corresponding author

Correspondence to Weishe Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Huang, J., Zhao, Y. et al. The preventive effects of aspirin on preeclampsia based on network pharmacology and bioinformatics. J Hum Hypertens 36, 753–759 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links