Skip to main content

Advertisement

SpringerLink
Log in

The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics

  • Maternal Fetal Medicine/Biology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Our previous study has shown that quercetin prevented lipopolysaccharide-induced preterm birth. This study aims to clarify the potential targets and biological mechanisms of quercetin in preventing preterm birth. We used bioinformatics databases to collect the candidate targets for quercetin and preterm birth. The biological functions and enriched pathways of the intersecting targets were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We obtained 105 targets for quercetin in preventing preterm birth. The biological processes of the intersecting targets are mainly involved in steroid metabolic process, drug metabolic process, oxidation-reduction process, omega-hydroxylase P450 pathway, positive regulation of cell migration, negative regulation of apoptotic process, and positive regulation of cell proliferation. The highly enriched pathways were steroid hormone biosynthesis, metabolism of xenobiotics by cytochrome P450, proteoglycans in cancer, focal adhesion, and arachidonic acid metabolism. The ten hub targets for quercetin in preventing preterm birth were AKT serine/threonine kinase 1, mitogen-activated protein kinase 3, epidermal growth factor receptor, prostaglandin-endoperoxide synthase 2, mitogen-activated protein kinase 1, estrogen receptor 1, heat shock protein 90 alpha family class A member 1, mitogen-activated protein kinase 8, androgen receptor, and matrix metallopeptidase 9. Molecular docking analysis showed good bindings between these proteins and quercetin. In conclusion, these findings highlight the key targets and molecular mechanisms of quercetin in preventing preterm birth.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of Data and Material

Data and material are available upon reasonable request.

Code Availability

Not applicable.

References

  1. Zierden HC, Ortiz JI, DeLong K, Yu J, Li G, Dimitrion P, et al. Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth. Sci Transl Med. 2021;13(576). https://doi.org/10.1126/scitranslmed.abc6245.

  2. He C, Liu L, Chu Y, Perin J, Dai L, Li X, et al. National and subnational all-cause and cause-specific child mortality in China, 1996-2015: a systematic analysis with implications for the Sustainable Development Goals. Lancet Glob Health. 2017;5(2):e186–e97. https://doi.org/10.1016/S2214-109X(16)30334-5.

    Article  PubMed  Google Scholar 

  3. Lappas M. The IL-1beta signalling pathway and its role in regulating pro-inflammatory and pro-labour mediators in human primary myometrial cells. Reprod Biol. 2017;17(4):333–40. https://doi.org/10.1016/j.repbio.2017.09.006.

    Article  PubMed  Google Scholar 

  4. Kemp MW. Preterm birth, intrauterine infection, and fetal inflammation. Front Immunol. 2014;5:574. https://doi.org/10.3389/fimmu.2014.00574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG : an international journal of obstetrics and gynaecology. 2006;113(Suppl 3):17–42. https://doi.org/10.1111/j.1471-0528.2006.01120.x.

    Article  CAS  Google Scholar 

  6. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345(6198):760–5. https://doi.org/10.1126/science.1251816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang Y, Quan F, Cao Q, Lin Y, Yue C, Bi R, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2021;28:231–43. https://doi.org/10.1016/j.jare.2020.07.007.

    Article  CAS  PubMed  Google Scholar 

  8. Revuelta MP, Hidalgo A, Cantabrana B. Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle. J Auton Pharmacol. 1999;19(6):353–8. https://doi.org/10.1111/j.1365-2680.1999.tb00008.x.

    Article  CAS  PubMed  Google Scholar 

  9. Vanhees K, Godschalk RW, Sanders A, van Waalwijk van Doorn-Khosrovani SB, van Schooten FJ. Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. Toxicology. 2011;290(2-3):350–8. https://doi.org/10.1016/j.tox.2011.10.017.

    Article  CAS  PubMed  Google Scholar 

  10. Liang C, DeCourcy K, Prater MR. High-saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice. Metab Clin Exp. 2010;59(7):943–50. https://doi.org/10.1016/j.metabol.2009.10.015.

    Article  CAS  PubMed  Google Scholar 

  11. Prater MR, Laudermilch CL, Liang C, Holladay SD. Placental oxidative stress alters expression of murine osteogenic genes and impairs fetal skeletal formation. Placenta. 2008;29(9):802–8. https://doi.org/10.1016/j.placenta.2008.06.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lin X, Peng Q, Zhang J, Li X, Huang J, Duan S, et al. Quercetin prevents lipopolysaccharide-induced experimental preterm labor in mice and increases offspring survival rate. Reprod Sci. 2020;27(4):1047–57. https://doi.org/10.1007/s43032-019-00034-3.

    Article  CAS  PubMed  Google Scholar 

  13. 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(8):1866–76. https://doi.org/10.7150/ijms.53685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tomaszewski P, Kubiak-Tomaszewska G, Pachecka J. Cytochrome P450 polymorphism--molecular, metabolic, and pharmacogenetic aspects. II. Participation of CYP isoenzymes in the metabolism of endogenous substances and drugs. Acta Pol Pharm. 2008;65(3):307–18.

    CAS  PubMed  Google Scholar 

  15. Haas DM, Quinney SK, McCormick CL, Jones DR, Renbarger JL. A pilot study of the impact of genotype on nifedipine pharmacokinetics when used as a tocolytic. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2012;25(4):419–23. https://doi.org/10.3109/14767058.2011.583700.

    Article  CAS  Google Scholar 

  16. Haas DM, Quinney SK, Clay JM, Renbarger JL, Hebert MF, Clark S, et al. Nifedipine pharmacokinetics are influenced by CYP3A5 genotype when used as a preterm labor tocolytic. Am J Perinatol. 2013;30(4):275–81. https://doi.org/10.1055/s-0032-1323590.

    Article  PubMed  Google Scholar 

  17. Xu L, Guo X, Li N, Pan Q, Ma YZ. Effects of quercetin on Aroclor 1254-induced expression of CYP450 and cytokines in pregnant rats. J Immunotoxicol. 2019;16(1):140–8. https://doi.org/10.1080/1547691X.2019.1604585.

    Article  CAS  PubMed  Google Scholar 

  18. Buhimschi IA, Buhimschi CS, Weiner CP. Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation. Am J Obstet Gynecol. 2003;188(1):203–8. https://doi.org/10.1067/mob.2003.112.

    Article  CAS  PubMed  Google Scholar 

  19. Tripathi A, Kumar B, Sagi SSK. Prophylactic efficacy of quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. PLoS One. 2019;14(6):e0219075. https://doi.org/10.1371/journal.pone.0219075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Iskusnykh IY, Buddington RK, Chizhikov VV. Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia. Exp Neurol. 2018;306:209–21. https://doi.org/10.1016/j.expneurol.2018.05.015.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bensley JG, Moore L, De Matteo R, Harding R, Black MJ. Impact of preterm birth on the developing myocardium of the neonate. Pediatr Res. 2018;83(4):880–8. https://doi.org/10.1038/pr.2017.324.

    Article  PubMed  Google Scholar 

  22. Chen Z, Yuan Q, Xu G, Chen H, Lei H, Su J. Effects of quercetin on proliferation and H(2)O(2)-induced apoptosis of intestinal porcine enterocyte cells. Molecules. 2018;23(8). https://doi.org/10.3390/molecules23082012.

  23. Wu X, Qu X, Zhang Q, Dong F, Yu H, Yan C, et al. Quercetin promotes proliferation and differentiation of oligodendrocyte precursor cells after oxygen/glucose deprivation-induced injury. Cell Mol Neurobiol. 2014;34(3):463–71. https://doi.org/10.1007/s10571-014-0030-4.

    Article  CAS  PubMed  Google Scholar 

  24. Yao JL, He QZ, Liu M, Chang XW, Wu JT, Duan T, et al. Effects of delta(9)-tetrahydrocannabinol (THC) on human amniotic epithelial cell proliferation and migration. Toxicology. 2018;394:19–26. https://doi.org/10.1016/j.tox.2017.11.016.

    Article  CAS  PubMed  Google Scholar 

  25. Rezabakhsh A, Rahbarghazi R, Malekinejad H, Fathi F, Montaseri A, Garjani A. Quercetin alleviates high glucose-induced damage on human umbilical vein endothelial cells by promoting autophagy. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;56:183–93. https://doi.org/10.1016/j.phymed.2018.11.008.

    Article  CAS  Google Scholar 

  26. Yan R, Tian H, Du Z. Quercetin protects PC-12 cells against hypoxia injury by down-regulation of miR-122. Iranian journal of basic medical sciences. 2019;22(4):391–8. https://doi.org/10.22038/ijbms.2019.30224.7287.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Demendi C, Borzsonyi B, Vegh V, Nagy ZB, Rigo J Jr, Pajor A, et al. Gene expression patterns of the Bcl-2 and Bax genes in preterm birth. Acta Obstet Gynecol Scand. 2012;91(10):1212–7. https://doi.org/10.1111/j.1600-0412.2012.01428.x.

    Article  CAS  PubMed  Google Scholar 

  28. Daher S, Guimaraes AJ, Mattar R, Ishigai MM, Barreiro EG, Bevilacqua E. Bcl-2 and Bax expressions in pre-term, term and post-term placentas. Am J Reprod Immunol. 2008;60(2):172–8. https://doi.org/10.1111/j.1600-0897.2008.00609.x.

    Article  PubMed  Google Scholar 

  29. Park DJ, Jeon SJ, Kang JB, Koh PO. Quercetin reduces ischemic brain injury by preventing ischemia-induced decreases in the neuronal calcium sensor protein hippocalcin. Neuroscience. 2020;430:47–62. https://doi.org/10.1016/j.neuroscience.2020.01.015.

    Article  CAS  PubMed  Google Scholar 

  30. Khan A, Ali T, Rehman SU, Khan MS, Alam SI, Ikram M, et al. Neuroprotective effect of quercetin against the detrimental effects of LPS in the adult mouse brain. Front Pharmacol. 2018;9:1383. https://doi.org/10.3389/fphar.2018.01383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cole TJ, Short KL, Hooper SB. The science of steroids. Semin Fetal Neonatal Med. 2019;24(3):170–5. https://doi.org/10.1016/j.siny.2019.05.005.

    Article  PubMed  Google Scholar 

  32. Fu L, Chen YH, Xu S, Yu Z, Zhang ZH, Zhang C, et al. Oral cholecalciferol supplementation alleviates lipopolysaccharide-induced preterm delivery partially through regulating placental steroid hormones and prostaglandins in mice. Int Immunopharmacol. 2019;69:235–44. https://doi.org/10.1016/j.intimp.2019.01.052.

    Article  CAS  PubMed  Google Scholar 

  33. Menon R, Jones J, Gunst PR, Kacerovsky M, Fortunato SJ, Saade GR, et al. Amniotic fluid metabolomic analysis in spontaneous preterm birth. Reprod Sci. 2014;21(6):791–803. https://doi.org/10.1177/1933719113518987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Santes-Palacios R, Marroquin-Perez AL, Hernandez-Ojeda SL, Camacho-Carranza R, Govezensky T, Espinosa-Aguirre JJ. Human CYP1A1 inhibition by flavonoids. Toxicology in vitro : an international journal published in association with BIBRA. 2020;62:104681. https://doi.org/10.1016/j.tiv.2019.104681.

    Article  CAS  Google Scholar 

  35. Zhou W, Yuan WF, Chen C, Wang SM, Liang SW. Study on material base and action mechanism of compound Danshen dripping pills for treatment of atherosclerosis based on modularity analysis. J Ethnopharmacol. 2016;193:36–44. https://doi.org/10.1016/j.jep.2016.07.014.

    Article  CAS  PubMed  Google Scholar 

  36. Pantham P, Armstrong DL, Bodnariuc J, Haupt O, Johnson AW, Underhill L, et al. Transcriptomic profiling of fetal membranes of mice deficient in biglycan and decorin as a model of preterm birth. Biol Reprod. 2020;104:611–23. https://doi.org/10.1093/biolre/ioaa205.

    Article  PubMed Central  Google Scholar 

  37. Atalay MA, Ozmen T, Demir BC, Kasapoglu I, Ozkaya G. Serum decorin measurement in prediction of the risk for preterm birth. Taiwanese journal of obstetrics & gynecology. 2018;57(1):23–7. https://doi.org/10.1016/j.tjog.2017.12.004.

    Article  Google Scholar 

  38. Borghi SM, Mizokami SS, Pinho-Ribeiro FA, Fattori V, Crespigio J, Clemente-Napimoga JT, et al. The flavonoid quercetin inhibits titanium dioxide (TiO2)-induced chronic arthritis in mice. J Nutr Biochem. 2018;53:81–95. https://doi.org/10.1016/j.jnutbio.2017.10.010.

    Article  CAS  PubMed  Google Scholar 

  39. Thiyagarajan V, Lin SH, Chia YC, Weng CF. A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking. Biochim Biophys Acta. 2013;1830(8):4091–101. https://doi.org/10.1016/j.bbagen.2013.04.027.

    Article  CAS  PubMed  Google Scholar 

  40. Chen HY, Gao LT, Yuan JQ, Zhang YJ, Liu P, Wang G, et al. Decrease in SHP-1 enhances myometrium remodeling via FAK activation leading to labor. Am J Physiol Endocrinol Metab. 2020;318(6):E930–E42. https://doi.org/10.1152/ajpendo.00068.2020.

    Article  CAS  PubMed  Google Scholar 

  41. Cao HH, Cheng CY, Su T, Fu XQ, Guo H, Li T, et al. Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration and invasion. Mol Cancer. 2015;14:103. https://doi.org/10.1186/s12943-015-0367-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Reece MS, McGregor JA, Allen KG, Harris MA. Maternal and perinatal long-chain fatty acids: possible roles in preterm birth. Am J Obstet Gynecol. 1997;176(4):907–14. https://doi.org/10.1016/s0002-9378(97)70620-3.

    Article  CAS  PubMed  Google Scholar 

  43. Menon R, Fortunato SJ, Milne GL, Brou L, Carnevale C, Sanchez SC, et al. Amniotic fluid eicosanoids in preterm and term births: effects of risk factors for spontaneous preterm labor. Obstet Gynecol. 2011;118(1):121–34. https://doi.org/10.1097/AOG.0b013e3182204eaa.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Peiris HN, Vaswani K, Holland O, Koh YQ, Almughlliq FB, Reed S, et al. Altered productions of prostaglandins and prostamides by human amnion in response to infectious and inflammatory stimuli identified by mutliplex mass spectrometry. Prostaglandins Leukot Essent Fat Acids. 2020;154:102059. https://doi.org/10.1016/j.plefa.2020.102059.

    Article  CAS  Google Scholar 

  45. Hirasawa N, Santini F, Beaven MA. Activation of the mitogen-activated protein kinase/cytosolic phospholipase A2 pathway in a rat mast cell line. Indications of different pathways for release of arachidonic acid and secretory granules. J Immunol. 1995;154(10):5391–402.

    CAS  PubMed  Google Scholar 

  46. Crescente M, Jessen G, Momi S, Holtje HD, Gresele P, Cerletti C, et al. Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies. Thromb Haemost. 2009;102(2):336–46. https://doi.org/10.1160/TH09-01-0057.

    Article  CAS  PubMed  Google Scholar 

  47. Guo H, Ren H, Liang S, Ji Y, Jiang H, Zhang P, et al. Phosphatidylinositol 3-kinase/Akt signal pathway resists the apoptosis and inflammation in human extravillous trophoblasts induced by Porphyromonas gingivalis. Mol Immunol. 2018;104:100–7. https://doi.org/10.1016/j.molimm.2018.10.008.

    Article  CAS  PubMed  Google Scholar 

  48. Nadeau-Vallee M, Boudreault A, Leimert K, Hou X, Obari D, Madaan A, et al. Uterotonic neuromedin U receptor 2 and its ligands are upregulated by inflammation in mice and humans, and elicit preterm birth. Biol Reprod. 2016;95(3):72. https://doi.org/10.1095/biolreprod.116.140905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Huang S, Zhu X, Huang W, He Y, Pang L, Lan X, et al. Quercetin inhibits pulmonary arterial endothelial cell transdifferentiation possibly by Akt and Erk1/2 pathways. Biomed Res Int. 2017;2017:6147294–8. https://doi.org/10.1155/2017/6147294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Garcia-Verdugo I, Leiber D, Robin P, Billon-Denis E, Chaby R, Tanfin Z. Direct interaction of surfactant protein A with myometrial binding sites: signaling and modulation by bacterial lipopolysaccharide. Biol Reprod. 2007;76(4):681–91. https://doi.org/10.1095/biolreprod.106.058131.

    Article  CAS  PubMed  Google Scholar 

  51. Mogami H, Kishore AH, Shi H, Keller PW, Akgul Y, Word RA. Fetal fibronectin signaling induces matrix metalloproteases and cyclooxygenase-2 (COX-2) in amnion cells and preterm birth in mice. J Biol Chem. 2013;288(3):1953–66. https://doi.org/10.1074/jbc.M112.424366.

    Article  CAS  PubMed  Google Scholar 

  52. Copley Salem C, Ulrich C, Quilici D, Schlauch K, Buxton ILO, Burkin H. Mechanical strain induced phospho-proteomic signaling in uterine smooth muscle cells. J Biomech. 2018;73:99–107. https://doi.org/10.1016/j.jbiomech.2018.03.040.

    Article  PubMed  Google Scholar 

  53. Chao PY, Huang YP, Hsieh WB. Inhibitive effect of purple sweet potato leaf extract and its components on cell adhesion and inflammatory response in human aortic endothelial cells. Cell Adhes Migr. 2013;7(2):237–45. https://doi.org/10.4161/cam.23649.

    Article  Google Scholar 

  54. Indra MR, Karyono S, Ratnawati R, Malik SG. Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in leptin-induced human umbilical vein endothelial cells (HUVECs). BMC research notes. 2013;6:275. https://doi.org/10.1186/1756-0500-6-275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gargiulo AR, Khan-Dawood FS, Dawood MY. Epidermal growth factor receptors in uteroplacental tissues in term pregnancy before and after the onset of labor. J Clin Endocrinol Metab. 1997;82(1):113–7. https://doi.org/10.1210/jcem.82.1.3671.

    Article  CAS  PubMed  Google Scholar 

  56. Knijnenburg TA, Vockley JG, Chambwe N, Gibbs DL, Humphries C, Huddleston KC, et al. Genomic and molecular characterization of preterm birth. Proc Natl Acad Sci U S A. 2019;116(12):5819–27. https://doi.org/10.1073/pnas.1716314116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kramer EL, Deutsch GH, Sartor MA, Hardie WD, Ikegami M, Korfhagen TR, et al. Perinatal increases in TGF-{alpha} disrupt the saccular phase of lung morphogenesis and cause remodeling: microarray analysis. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L314–27. https://doi.org/10.1152/ajplung.00354.2006.

    Article  CAS  PubMed  Google Scholar 

  58. Hanikoglu A, Kucuksayan E, Hanikoglu F, Ozben T, Menounou G, Sansone A, et al. Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes. Can J Physiol Pharmacol. 2020;98(3):131–8. https://doi.org/10.1139/cjpp-2019-0352.

    Article  CAS  PubMed  Google Scholar 

  59. Cuevas MJ, Tieppo J, Marroni NP, Tunon MJ, Gonzalez-Gallego J. Suppression of amphiregulin/epidermal growth factor receptor signals contributes to the protective effects of quercetin in cirrhotic rats. J Nutr. 2011;141(7):1299–305. https://doi.org/10.3945/jn.111.140954.

    Article  CAS  PubMed  Google Scholar 

  60. Littauer EQ, Skountzou I. Hormonal regulation of physiology, innate immunity and antibody response to H1N1 influenza virus infection during pregnancy. Front Immunol. 2018;9:2455. https://doi.org/10.3389/fimmu.2018.02455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hao K, Xu X, Laird N, Wang X, Xu X. Power estimation of multiple SNP association test of case-control study and application. Genet Epidemiol. 2004;26(1):22–30. https://doi.org/10.1002/gepi.10293.

    Article  PubMed  Google Scholar 

  62. Wu WX, Ma XH, Yoshizato T, Shinozuka N, Nathanielsz PW. Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor alpha and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor. Endocrinology. 1999;140(12):5712–8. https://doi.org/10.1210/endo.140.12.7201.

    Article  CAS  PubMed  Google Scholar 

  63. Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316–26. https://doi.org/10.1016/j.reprotox.2020.07.015.

    Article  CAS  PubMed  Google Scholar 

  64. Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G. Modulation of osteoclastogenesis in porcine bone marrow cultures by quercetin and rutin. Cell Tissue Res. 2005;319(3):383–93. https://doi.org/10.1007/s00441-004-1053-9.

    Article  CAS  PubMed  Google Scholar 

  65. Kiyga E, Sengelen A, Adiguzel Z, Onay UE. Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells. Mol Biol Rep. 2020;47(7):4957–67. https://doi.org/10.1007/s11033-020-05641-x.

    Article  CAS  PubMed  Google Scholar 

  66. Pirianov G, MacIntyre DA, Lee Y, Waddington SN, Terzidou V, Mehmet H, et al. Specific inhibition of c-Jun N-terminal kinase delays preterm labour and reduces mortality. Reproduction. 2015;150(4):269–77. https://doi.org/10.1530/REP-15-0258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Mu MM, Chakravortty D, Sugiyama T, Koide N, Takahashi K, Mori I, et al. The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. J Endotoxin Res. 2001;7(6):431–8. https://doi.org/10.1179/096805101101533034.

    Article  CAS  PubMed  Google Scholar 

  68. Karjalainen MK, Huusko JM, Ulvila J, Sotkasiira J, Luukkonen A, Teramo K, et al. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers. PLoS One. 2012;7(12):e51378. https://doi.org/10.1371/journal.pone.0051378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Abarikwu SO, Pant AB, Farombi EO. Effects of quercetin on mRNA expression of steroidogenesis genes in primary cultures of Leydig cells treated with atrazine. Toxicology in vitro : an international journal published in association with BIBRA. 2013;27(2):700–7. https://doi.org/10.1016/j.tiv.2012.11.005.

    Article  CAS  Google Scholar 

  70. Ulrich CC, Arinze V, Wandscheer CB, Copley Salem C, Nabati C, Etezadi-Amoli N, et al. Matrix metalloproteinases 2 and 9 are elevated in human preterm laboring uterine myometrium and exacerbate uterine contractilitydagger. Biol Reprod. 2019;100(6):1597–604. https://doi.org/10.1093/biolre/ioz054.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Sundrani D, Narang A, Mehendale S, Joshi S, Chavan-Gautam P. Investigating the expression of MMPs and TIMPs in preterm placenta and role of CpG methylation in regulating MMP-9 expression. IUBMB Life. 2017;69(12):985–93. https://doi.org/10.1002/iub.1687.

    Article  CAS  PubMed  Google Scholar 

  72. Wu TC, Chan ST, Chang CN, Yu PS, Chuang CH, Yeh SL. Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-kappaB signaling in A549cells. Chem Biol Interact. 2018;292:101–9. https://doi.org/10.1016/j.cbi.2018.07.010.

    Article  CAS  PubMed  Google Scholar 

  73. Lan H, Hong W, Fan P, Qian D, Zhu J, Bai B. Quercetin inhibits cell migration and invasion in human osteosarcoma cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;43(2):553–67. https://doi.org/10.1159/000480528.

    Article  CAS  Google Scholar 

  74. Ballmann C, Denney TS, Beyers RJ, Quindry T, Romero M, Amin R, et al. Lifelong quercetin enrichment and cardioprotection in Mdx/Utrn+/- mice. Am J Physiol Heart Circ Physiol. 2017;312(1):H128–H40. https://doi.org/10.1152/ajpheart.00552.2016.

    Article  PubMed  Google Scholar 

Download references

Funding

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

  1. Department of Obstetrics, Xiangya Hospital, Central South University, No.87 XiangYa Road, Changsha, 410078, Hunan Province, China

    Jiejie Zhang, Qiaozhen Peng, Yaping Deng, Manling Sun, Yanhua Zhao & Weishe Zhang

  2. Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, China

    Jiejie Zhang & Weishe Zhang

Authors
  1. Jiejie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiaozhen Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaping Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manling Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanhua Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weishe Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weishe Zhang.

Ethics declarations

Ethics Approval

This study was approved by the Medical Ethics Committee of Xiangya Hospital Central South University (approval ID: 202012232).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

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

ESM 1

(DOC 77 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Peng, Q., Deng, Y. et al. The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics. Reprod. Sci. 29, 193–202 (2022). https://doi.org/10.1007/s43032-021-00674-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00674-4

Keywords

Search

Navigation