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Volume 31, Issue 35
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286
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Abstract

Background

Qu’s formula 6 (QUF6), a patented Chinese herbal medicine, is used to treat hypothyroidism in the context of fertilization-embryo transfer (IVF-ET). This research aims to identify the potential bioactive components and elucidate the underlying molecular mechanisms by which QUF6 cures hypothyroidism during IVF-ET.

Materials and Methods

To find the active components of QUF6, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant literature were searched. GeneCards and other resources were used to find the targets associated with hypothyroidism and IVF-ET. Using Cytoscape software, the network of interactions was created between the targets and components, the protein-protein interaction (PPI) network was built, and significant targets were verified. Afterward, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on crucial targets. Finally, molecular docking and dynamic modeling were carried out to analyze the essential components and core targets of QUF6.

Results

By creating an interaction network, it was discovered that 92 active components in QUF6 can operate on 25 disease-related targets, with quercetin and other components playing important pharmacodynamic roles. Tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1B (IL-1B), apoptosis regulator Bcl-2 (BCL2), prostaglandin G/H synthase 2 (PTGS2), cellular tumor antigen p53 (TP53), and epidermal growth factor (EGF) were the main targets for the therapy of hypothyroidism. The KEGG pathway enrichment study identified 91 signaling pathways, whereas the GO enrichment analysis identified 1608 entries. Through molecular docking and MD simulations, stable binding was identified between the top five active constituents and the top seven potential targets.

Conclusion

Quercetin, beta-sitosterol, kaempferol, 7-ketocholesterol, and rehmapicrogenin were determined to be the active ingredients in QUF6. The potential mechanism of action for QUF6 may involve modulation of TNF, IL6, IL1B, BCL2, PTSG2, TP53, and EGF to regulate oxidative stress levels, inflammation responses, and apoptosis processes associated with hypothyroidism during IVF-ET.

© 2025 The Author(s). Published by Bentham Science Publisher.
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References

  1. BucciI. GiulianiC. Di DalmaziG. FormosoG. NapolitanoG. Thyroid autoimmunity in female infertility and assisted reproductive technology outcome.Front. Endocrinol.20221376836310.3389/fendo.2022.768363 35721757
     [Google Scholar]
  2. ZamwarU.M. MuneshwarK.N. Epidemiology, types, causes, clinical presentation, diagnosis, and treatment of hypothyroidism.Cureus2023159e4624110.7759/cureus.46241 37908940
     [Google Scholar]
  3. RedmondG.P. Thyroid dysfunction and women’s reproductive health.Thyroid200414Suppl. 151510.1089/105072504323024543 15142372
     [Google Scholar]
  4. BrownE.D.L. Obeng-GyasiB. HallJ.E. ShekharS. The thyroid hormone axis and female reproduction.Int. J. Mol. Sci.20232412981510.3390/ijms24129815 37372963
     [Google Scholar]
  5. UnnikrishnanA. KalraS. SahayR. BantwalG. JohnM. TewariN. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India.Indian J. Endocrinol. Metab.201317464765210.4103/2230‑8210.113755 23961480
     [Google Scholar]
  6. OrsuP. KoyyadaA. Role of hypothyroidism and associated pathways in pregnancy and infertility: Clinical insights.Tzu-Chi Med. J.202032431231710.4103/tcmj.tcmj_255_19 33163375
     [Google Scholar]
  7. ZhangC. GuoL. ZhuB. Effects of 3, 5, 3′-triiodothyronine (t3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells.Chin. J. Physiol.201356529830510.4077/CJP.2013.BAB186 24032715
     [Google Scholar]
  8. CramerD.W. SlussP.M. PowersR.D. Serum prolactin and TSH in an in vitro fertilization population: Is there a link between fertilization and thyroid function?J. Assist. Reprod. Genet.200320621021510.1023/A:1024151210536 12877251
     [Google Scholar]
  9. KarmonA.E. CardozoE.R. SouterI. GoldJ. PetrozzaJ.C. StyerA.K. Donor TSH level is associated with clinical pregnancy among oocyte donation cycles.J. Assist. Reprod. Genet.201633448949410.1007/s10815‑016‑0668‑6 26847132
     [Google Scholar]
  10. MansourianA.R. Abnormal serum thyroid hormones concentration with healthy functional gland: A review on the metabolic role of thyroid hormones transporter proteins.Pak. J. Biol. Sci.201114531332610.3923/pjbs.2011.313.326 21874823
     [Google Scholar]
  11. PoppeK. GlinoerD. TournayeH. DevroeyP. VelkeniersB. Impact of the ovarian hyperstimulation syndrome on thyroid function.Thyroid200818780180210.1089/thy.2007.0304 18631013
     [Google Scholar]
  12. AndrisaniA. SabbadinC. MarinL. The influence of thyroid autoimmunity on embryo quality in women undergoing assisted reproductive technology.Gynecol. Endocrinol.201834975275510.1080/09513590.2018.1442427 29463152
     [Google Scholar]
  13. InagakiY. TakeshimaK. NishiM. The influence of thyroid autoimmunity on pregnancy outcome in infertile women: A prospective study.Endocr. J.202067885986810.1507/endocrj.EJ19‑0604 32336697
     [Google Scholar]
  14. Repelaer van Driel-DelpratC.C. van DamE.W.C.M. van de VenP.M. Thyroid function and IVF outcome for different indications of subfertility.Reprod. Fertil.20212428029110.1530/RAF‑20‑0065 35118405
     [Google Scholar]
  15. ShawN.D. HistedS.N. SroujiS.S. Estrogen negative feedback on gonadotropin secretion: Evidence for a direct pituitary effect in women.J. Clin. Endocrinol. Metab.20109541955196110.1210/jc.2009‑2108
     [Google Scholar]
  16. ThangaratinamS. TanA. KnoxE. KilbyM.D. FranklynJ. CoomarasamyA. Association between thyroid autoantibodies and miscarriage and preterm birth: Meta-analysis of evidence.BMJ2011342d261610.1136/bmj.d2616 21558126
     [Google Scholar]
  17. PoppeK. BisschopP. FugazzolaL. MinzioriG. UnuaneD. WeghoferA. 2021 european thyroid association guideline on thyroid disorders prior to and during assisted reproduction.Eur. Thyroid J.20209628129510.1159/000512790 33718252
     [Google Scholar]
  18. LuoQ. FangZ.H. Clinical research progress in traditional chinese medicine treatment of hypothyroidism.Clin J Tradit Chin Med201931112181218410.16448/j.cjtcm.2019.0632
     [Google Scholar]
  19. RuJ. LiP. WangJ. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑13 24735618
     [Google Scholar]
  20. XiongW. WuH. XiongY. Network pharmacology-based research of active components of albiziae flos and mechanisms of its antidepressant effect.Curr. Med. Sci.202040112312910.1007/s11596‑020‑2155‑7 32166674
     [Google Scholar]
  21. LiuZ. GuoF. WangY. BATMAN-TCM: A bioinformatics analysis tool for molecular mechanism of traditional chinese medicine.Sci. Rep.2016612114610.1038/srep21146 26879404
     [Google Scholar]
  22. LiB. TaoW. ZhengC. Systems pharmacology-based approach for dissecting the addition and subtraction theory of traditional Chinese medicine: An example using Xiao-Chaihu-Decoction and Da-Chaihu-Decoction.Comput. Biol. Med.201453192910.1016/j.compbiomed.2014.05.007 25105750
     [Google Scholar]
  23. Unit Prot ConsortiumUniProt: A worldwide hub of protein knowledge.Nucleic Acids Res.201947D1D506D51510.1093/nar/gky1049 30395287
     [Google Scholar]
  24. StelzerG RosenN PlaschkesI. The genecards suite: From gene data mining to disease genome sequence analyses.Curr Protoc Bioinformatics2016541.30.3131.30.3310.1002/cpbi.5
     [Google Scholar]
  25. AmbergerJ.S. BocchiniC.A. SchiettecatteF. ScottA.F. HamoshA. OMIM.org: Online mendelian inheritance in man (OMIM®), an online catalog of human genes and genetic disorders.Nucleic Acids Res.201543D1D789D79810.1093/nar/gku1205 25428349
     [Google Scholar]
  26. KnoxC. WilsonM. KlingerC.M. DrugBank 6.0: The drugbank knowledgebase for 2024.Nucleic Acids Res.202452D1D1265D127510.1093/nar/gkad976 37953279
     [Google Scholar]
  27. ShannonP. MarkielA. OzierO. Cytoscape: A software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.1239303 14597658
     [Google Scholar]
  28. SzklarczykD. MorrisJ.H. CookH. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible.Nucleic Acids Res.201745D1D362D36810.1093/nar/gkw937 27924014
     [Google Scholar]
  29. ZhangW TianW WangY Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer based on network pharmacology and molecular docking.Comput Biol Med2022151Ptl A10629310.1016/j.compbiomed.2022.106293
     [Google Scholar]
  30. DennisG.Jr ShermanB.T. HosackD.A. DAVID: Database for annotation, visualization, and integrated discovery.Genome Biol.200345P310.1186/gb‑2003‑4‑5‑p3 12734009
     [Google Scholar]
  31. EberhardtJ. Santos-MartinsD. TillackA.F. ForliS. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings.J. Chem. Inf. Model.20216183891389810.1021/acs.jcim.1c00203 34278794
     [Google Scholar]
  32. SeeligerD. de GrootB.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina.J. Comput. Aided Mol. Des.201024541742210.1007/s10822‑010‑9352‑6 20401516
     [Google Scholar]
  33. BurleyS.K. BermanH.M. KleywegtG.J. MarkleyJ.L. NakamuraH. VelankarS. Protein data bank (PDB): The single global macromolecular structure archive.Methods Mol. Biol.2017160762764110.1007/978‑1‑4939‑7000‑1_26 28573592
     [Google Scholar]
  34. YeJ. LiL. HuZ. Exploring the molecular mechanism of action of yinchen wuling powder for the treatment of hyperlipidemia, using network pharmacology, molecular docking, and molecular dynamics simulation.BioMed Res. Int.2021202111410.1155/2021/9965906 34746316
     [Google Scholar]
  35. LiaoF. YousifM. HuangR. QiaoY. HuY. Network pharmacology- and molecular docking-based analyses of the antihypertensive mechanism of Ilex kudingcha.Front. Endocrinol.202314121608610.3389/fendo.2023.1216086 37664830
     [Google Scholar]
  36. BerendsenH.J.C. van der SpoelD. van DrunenR. GROMACS: A message-passing parallel molecular dynamics implementation.Comput. Phys. Commun.1995911-3435610.1016/0010‑4655(95)00042‑E
     [Google Scholar]
  37. YanaoT. KoonW.S. MarsdenJ.E. KevrekidisI.G. Gyration-radius dynamics in structural transitions of atomic clusters.J. Chem. Phys.20071261212410210.1063/1.2710272 17411103
     [Google Scholar]
  38. GaoJ. ZhengS. YaoM. WuP. Precise estimation of residue relative solvent accessible area from Cα atom distance matrix using a deep learning method.Bioinformatics2021381949810.1093/bioinformatics/btab616 34450651
     [Google Scholar]
  39. MaruyamaY. IgarashiR. UshikuY. MitsutakeA. Analysis of protein folding simulation with moving root mean square deviation.J. Chem. Inf. Model.20236351529154110.1021/acs.jcim.2c01444 36821519
     [Google Scholar]
  40. FatriansyahJ.F. RizqillahR.K. YandiM.Y. Fadilah SahlanM. Molecular docking and dynamics studies on propolis sulabiroin-A as a potential inhibitor of SARS-CoV-2.J. King Saud Univ. Sci.202234110170710.1016/j.jksus.2021.101707 34803333
     [Google Scholar]
  41. Carretero-GonzálezR. KevrekidisP.G. KevrekidisI.G. MaroudasD. FrantzeskakisD.J. A Parrinello-Rahman approach to vortex lattices.Phys. Lett. A20053411-412813410.1016/j.physleta.2005.04.046
     [Google Scholar]
  42. Valdés-TresancoM.S. Valdés-TresancoM.E. ValienteP.A. MorenoE. gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS.J. Chem. Theory Comput.202117106281629110.1021/acs.jctc.1c00645 34586825
     [Google Scholar]
  43. HsinK.Y. GhoshS. KitanoH. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology.PLoS One2013812e8392210.1371/journal.pone.0083922 24391846
     [Google Scholar]
  44. MintzioriG. AnagnostisP. ToulisK.A. GoulisD.G. Thyroid diseases and female reproduction.Minerva Med.201210314762 22278068
     [Google Scholar]
  45. TudosaR. VartejP. HorhoianuI. GhicaC. MateescuS. DumitracheI. Maternal and fetal complications of the hypothyroidism-related pregnancy.Maedica201052116123 21977134
     [Google Scholar]
  46. GlinoerD. DelangeF. The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny.Thyroid2000101087188710.1089/thy.2000.10.871 11081254
     [Google Scholar]
  47. KimC.H. AhnJ.W. KangS.P. KimS.H. ChaeH.D. KangB.M. Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection.Fertil. Steril.20119551650165410.1016/j.fertnstert.2010.12.004 21193190
     [Google Scholar]
  48. ArdabiliN.S. RahimiF. RanjbarA. MontazeriF. DarsarehF. Maternal and neonatal outcomes of sub-clinical hypothyroidism treated with levothyroxine in pregnancy: A retrospective cohort study.Cureus2023159e4535210.7759/cureus.45352 37849597
     [Google Scholar]
  49. LengT. LiX. ZhangH. Levothyroxine treatment for subclinical hypothyroidism improves the rate of live births in pregnant women with recurrent pregnancy loss: A randomized clinical trial.Gynecol. Endocrinol.202238648849410.1080/09513590.2022.2063831 35426326
     [Google Scholar]
  50. JonklaasJ. BiancoA.C. BauerA.J. Guidelines for the treatment of hypothyroidism: Prepared by the American thyroid association task force on thyroid hormone replacement.Thyroid201424121670175110.1089/thy.2014.0028 25266247
     [Google Scholar]
  51. HeJ. ZhouY. ZhangT. ZouY. HuangH. Effect of Bushen Antai recipe on pyroptosis mechanism of subclinical hypothyroidism decidual cells in early pregnancy.Ann. Transl. Med.20221020110110.21037/atm‑22‑4079 36388780
     [Google Scholar]
  52. GaoD. JiangS.L. DingJ.P. Clinical study of traditional Chinese medicine combined with acupuncture and moxibustion in the treatment of pregnancy combined with hypothyroidism.New Chinese Medicine20215318767910.13457/j.cnki.jncm.2021.18.021
     [Google Scholar]
  53. ChenY. ZhouZ. LiX.X. WangT. Research on the protective effects of antioxidants on metabolic syndrome induced by thyroid dysfunction.Eur. Rev. Med. Pharmacol. Sci.20182218576510.26355/eurrev_201809_15896 30280806
     [Google Scholar]
  54. BadrG.M. ElsawyH. SedkyA. Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats.Environ. Sci. Pollut. Res. Int.20192688202821110.1007/s11356‑019‑04276‑1 30697654
     [Google Scholar]
  55. ChandraR. SinghS. GangulyC. β-Sitosterol & quercetin enhances brain development in iodine deficient rat models.Nutr. Health2022260106022112220910.1177/02601060221122209 36017551
     [Google Scholar]
  56. da-SilvaW.S. HarneyJ.W. KimB.W. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation.Diabetes200756376777610.2337/db06‑1488 17327447
     [Google Scholar]
  57. ManciniA. Di SegniC. RaimondoS. Thyroid hormones, oxidative stress, and inflammation.Mediators Inflamm.2016201611210.1155/2016/6757154 27051079
     [Google Scholar]
  58. ÜnlütürkU. SavaşM. OğuzS.H. Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.Clin. Biochem.202193737910.1016/j.clinbiochem.2021.04.007 33861988
     [Google Scholar]
  59. WangM. KeY. LiY. The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro.Biomed. Pharmacother.202113811130510.1016/j.biopha.2021.111305 33820633
     [Google Scholar]
  60. WuB. XuY. BanY. Correlation between the intestinal microflora and peripheral blood Th1/Th2 balance in hypothyroidism during the first half of pregnancy.Front. Cell. Infect. Microbiol.202313115923810.3389/fcimb.2023.1159238 37051293
     [Google Scholar]
  61. DabasA. SinghH. GoswamiB. Thyroid dysfunction in covid-19.Indian J. Endocrinol. Metab.202125519820110.4103/ijem.ijem_195_21 34760673
     [Google Scholar]
  62. PapanasN. PapazoglouD. PapatheodorouK. AntonoglouC. KotsiouS. MaltezosE. Thyroxine replacement dose in patients with Hashimoto disease: A potential role for interleukin-6.Cytokine2006353-416617010.1016/j.cyto.2006.07.017 16949834
     [Google Scholar]
  63. RasmussenA.K. Cytokine actions on the thyroid gland.Dan. Med. Bull.200047294114 10822801
     [Google Scholar]
  64. NechiporukT. KurtzS.E. NikolovaO. The TP53 apoptotic network is a primary mediator of resistance to BCL2 inhibition in AML cells.Cancer Discov.20199791092510.1158/2159‑8290.CD‑19‑0125 31048320
     [Google Scholar]
  65. LiuY. ChenH. ZhangL. ZhangT. RenX. The association between thyroid injury and apoptosis, and alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein expression induced by nickel sulfate in wistar rats.Biol. Trace Elem. Res.2020195115916810.1007/s12011‑019‑01825‑0 31392545
     [Google Scholar]
  66. PreziosoG. GianniniC. ChiarelliF. Effect of thyroid hormones on neurons and neurodevelopment.Horm. Res. Paediatr.2018902738110.1159/000492129 30157487
     [Google Scholar]
  67. WangX. SimpsonE.R. BrownK.A. p53: Protection against tumor growth beyond effects on cell cycle and apoptosis.Cancer Res.201575235001500710.1158/0008‑5472.CAN‑15‑0563 26573797
     [Google Scholar]
  68. YanH. HuangW. RaoJ. YuanJ. miR-21 regulates ischemic neuronal injury via the p53/Bcl-2/Bax signaling pathway.Aging (Albany NY)20211318222422225510.18632/aging.203530 34552038
     [Google Scholar]
  69. WeiX. TanJ. GaoH. Role of sirtuin 1 in the brain development in congenital hypothyroidism rats via the regulation of p53 signaling pathway.Bioengineered20221349455946610.1080/21655979.2022.2060626 35383535
     [Google Scholar]
  70. BoutinA. Marcus-SamuelsB. EliseevaE. NeumannS. GershengornM.C. Opposing effects of EGF receptor signaling on proliferation and differentiation initiated by EGF or TSH/EGF receptor transactivation.Endocrinology202216312bqac13610.1210/endocr/bqac136 36281035
     [Google Scholar]
  71. GoodmanC. JeyendranR.S. CoulamC.B. P53 tumor suppressor factor, plasminogen activator inhibitor, and vascular endothelial growth factor gene polymorphisms and recurrent implantation failure.Fertil. Steril.200992249449810.1016/j.fertnstert.2008.07.022 18829023
     [Google Scholar]
  72. ChanY. ZhuB. JiangH. ZhangJ. LuoY. TangW. Influence of TP53 codon 72 polymorphism alone or in combination with HDM2 SNP309 on human infertility and IVF outcome.PLoS One20161111e016714710.1371/journal.pone.0167147 27898708
     [Google Scholar]
  73. PalomaresA.R. Castillo-DomínguezA.A. Ruiz-GaldónM. Rodriguez-WallbergK.A. Reyes-EngelA. Genetic variants in the p53 pathway influence implantation and pregnancy maintenance in IVF treatments using donor oocytes.J. Assist. Reprod. Genet.202138123267327510.1007/s10815‑021‑02324‑9 34618298
     [Google Scholar]
  74. VishwakarmaJ. GuptaK. MishraJ. Hypothyroidism induces motor deficit via altered cerebellar HB-EGF/EGFR and autophagy.J. Endocrinol.20232571e22033810.1530/JOE‑22‑0338 36655849
     [Google Scholar]
  75. NingY. ChengY.J. LiuL.J. What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants.BMC Med.20171512110.1186/s12916‑017‑0777‑9 28148249
     [Google Scholar]
  76. Al HelaliS. HanifM.A. AlshugairN. Associations between hypothyroidism and subclinical atherosclerosis among male and female patients without clinical disease referred to computed tomography.Endocr. Pract.2023291293594110.1016/j.eprac.2023.08.012 37890618
     [Google Scholar]
  77. CalloniG.W. PennoC.A. CordovaF.M. TrentinA.G. NetoV.M. LealR.B. Congenital hypothyroidism alters the phosphorylation of ERK1/2 and p38MAPK in the hippocampus of neonatal rats.Brain Res. Dev. Brain Res.2005154114114510.1016/j.devbrainres.2004.10.005 15617763
     [Google Scholar]
  78. AminS.A. AdhikariN. GayenS. JhaT. Insight into the structural requirements of theophylline-based aldehyde dehydrogenase lAl (ALDHlAl) inhibitors through multi-QSAR modeling and molecular docking approaches.Curr. Drug Discov. Technol.20161328410010.2174/1570163813666160429115628 27132720
     [Google Scholar]
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Mechanisms of a Patented Chinese Herbal Medicine for Treating Hypothyroidism in In Vitro Fertilization-Embryo Transfer: A Combination of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation
Curr. Pharm. Des. 31, 2849 (2025); https://doi.org/10.2174/0113816128364578250212094405
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  • Article Type:     Research Article
Keyword(s): Chinese herbal medicine; hypothyroidism; in vitro fertilization-embryo transfer; molecular docking; molecular dynamics simulation; network pharmacology

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