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2000
Volume 20, Issue 8
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Background

Zhengsui Wan (ZSW) is a commonly used traditional Chinese medicine formula for treating Acute Lymphatic Leukemia (ALL) in our institution, and it has shown potential efficacy. However, its mechanism of action (MoA) remains unclear. In this study, we systematically explored the ZSW in ALL ( and ) using network pharmacology and molecular docking techniques.

Methods

Mass spectrometry was conducted to analyze possible active components in ZSW. BALB/c mice were treated by ZSW aqueous decoction, and mesenchymal stem cells (MSCs) were extracted for proteomic analysis to evaluate differentially expressed proteins. Moreover, proteins associated with acute lymphoblastic leukemia in SwissTargetPrediction and GeneCards databases were screened, and they intersected with differentially expressed proteins to obtain potential targets for ZSW. Protein interactions were constructed for the selected targets. Then, we performed GO and KEGG enrichment analysis on its basis and screened the core target through K-core. We validated it by molecular docking with the top three actives in the molecular network in degree value. Finally, we detected the regulation of ICAM1 in MSCs by ZSW by qRT-PCR.

Results

We detected 182 active ingredients in ZSW and identified 725 differential proteins in ZSW-treated mice, of which 25 were potential targets. Furthermore, MMP2, ICAM1, PSEN1, SLC9A1, and MMP14 were identified as core targets using the PPI network and K-core screening. Moreover, ZSW significantly downregulated ICAM1 expression in MSCs. GO and KEGG enrichment analyses showed that the results of ZSW were coordinated through immunomodulatory, inflammation-related, and drug resistance-related genes, including the PI3K-Akt, cAMP, and Wnt signaling pathways. Molecular docking and molecular dynamics simulations indicated moderate binding capacity between the active compounds and the screened target.

Conclusion

In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.

© 2025 Bentham Science Publishers
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2024-12-12
2026-01-09

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References

  1. ZhangN. WuJ. WangQ. Global burden of hematologic malignancies and evolution patterns over the past 30 years.Blood Cancer J.20231318210.1038/s41408‑023‑00853‑3 37193689
     [Google Scholar]
  2. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.21763 36633525
     [Google Scholar]
  3. PagliaroL. ChenS.J. HerranzD. Acute lymphoblastic leukaemia.Nat. Rev. Dis. Primers20241014110.1038/s41572‑024‑00525‑x 38871740
     [Google Scholar]
  4. den BoerM.L. CarioG. MoormanA.V. Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: A multicentre, retrospective, cohort study.Lancet Haematol.202181e55e6610.1016/S2352‑3026(20)30353‑7 33357483
     [Google Scholar]
  5. Abou DalleI. AtouiA. BazarbachiA. The elephant in the room: AML relapse post allogeneic hematopoietic cell transplantation.Front. Oncol.20221179327410.3389/fonc.2021.793274 35047405
     [Google Scholar]
  6. TanZ. KanC. WongM. Regulation of malignant myeloid leukemia by mesenchymal stem cells.Front. Cell Dev. Biol.20221085704510.3389/fcell.2022.857045 35756991
     [Google Scholar]
  7. ParkC.S. YoshiharaH. GaoQ. Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia.Cell Rep.202342711280410.1016/j.celrep.2023.112804 37453060
     [Google Scholar]
  8. FallatiA. Di MarzoN. D’AmicoG. DanderE. Mesenchymal stromal cells (MSCs): An ally of B-cell acute Lymphoblastic Leukemia (B-ALL) cells in disease maintenance and progression within the bone marrow Hematopoietic Niche.Cancers (Basel)20221414330310.3390/cancers14143303 35884364
     [Google Scholar]
  9. Peter MuiruriK. ZhongJ. YaoB. LaiR. LuoL. Bioactive peptides from scorpion venoms: Therapeutic scaffolds and pharmacological tools.Chin. J. Nat. Med.2023211193510.1016/S1875‑5364(23)60382‑6 36641229
     [Google Scholar]
  10. MaY. ZhouK. FanJ. SunS. Traditional Chinese medicine: Potential approaches from modern dynamical complexity theories.Front. Med.2016101283210.1007/s11684‑016‑0434‑2 26809465
     [Google Scholar]
  11. TavassolyI. GoldfarbJ. IyengarR. Systems biology primer: The basic methods and approaches.Essays Biochem.201862448750010.1042/EBC20180003 30287586
     [Google Scholar]
  12. SchubertM. KlingerB. KlünemannM. Perturbation-response genes reveal signaling footprints in cancer gene expression.Nat. Commun.2018912010.1038/s41467‑017‑02391‑6 29295995
     [Google Scholar]
  13. 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]
  14. DainaA. MichielinO. ZoeteV. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules.Nucleic Acids Res.201947W1W357-6410.1093/nar/gkz382 31106366
     [Google Scholar]
  15. FishilevichS. NudelR. RappaportN. GeneHancer: Genome-wide integration of enhancers and target genes in GeneCards.Database (Oxford)20172017bax02810.1093/database/bax028 28605766
     [Google Scholar]
  16. Demeter-HaludkaV. KovácsM. PetrusA. Examination of the role of mitochondrial morphology and function in the cardioprotective effect of sodium nitrite administered 24 h before Ischemia/Reperfusion injury.Front. Pharmacol.2018928610.3389/fphar.2018.00286 29643809
     [Google Scholar]
  17. MoulderR. BhosaleS.D. GoodlettD.R. LahesmaaR. Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling.Mass Spectrom. Rev.201837558360610.1002/mas.21550 29120501
     [Google Scholar]
  18. GruszkaA.M. ValliD. AlcalayM. Wnt signalling in acute myeloid leukaemia.Cells2019811140310.3390/cells8111403 31703382
     [Google Scholar]
  19. El-DydamonyN.M. AbdelnabyR.M. AbdelhadyR. Pyrimidine-5-carbonitrile based potential anticancer agents as apoptosis inducers through PI3K/AKT axis inhibition in leukaemia K562.J. Enzyme Inhib. Med. Chem.202237189591110.1080/14756366.2022.2051022 35345960
     [Google Scholar]
  20. ShayoC. LegnazziB.L. MonczorF. The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation.Biochem. Biophys. Res. Commun.2004314379880410.1016/j.bbrc.2003.12.166 14741706
     [Google Scholar]
  21. García-AlgarraJ. PastorJ.M. IriondoJ.M. GaleanoJ. Ranking of critical species to preserve the functionality of mutualistic networks using the k -core decomposition.PeerJ20175e332110.7717/peerj.3321 28533969
     [Google Scholar]
  22. TerwilligerT. Abdul-HayM. Acute lymphoblastic leukemia: A comprehensive review and 2017 update.Blood Cancer J.201776e57710.1038/bcj.2017.53 28665419
     [Google Scholar]
  23. De KouchkovskyI. Abdul-HayM. ‘Acute myeloid leukemia: A comprehensive review and 2016 update’.Blood Cancer J.201667e44110.1038/bcj.2016.50 27367478
     [Google Scholar]
  24. FreyN.V. ShawP.A. HexnerE.O. Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia.J. Clin. Oncol.202038541542210.1200/JCO.19.01892 31815579
     [Google Scholar]
  25. WinerE.S. StoneR.M. Novel therapy in Acute myeloid leukemia (AML): Moving toward targeted approaches.Ther. Adv. Hematol.201910204062071986064510.1177/2040620719860645 31321011
     [Google Scholar]
  26. ForteD. García-FernándezM. Sánchez-AguileraA. Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy.Cell Metab.2020325829843.e910.1016/j.cmet.2020.09.001 32966766
     [Google Scholar]
  27. YuanH. MaQ. CuiH. How can synergism of traditional medicines benefit from network pharmacology?Molecules2017227113510.3390/molecules22071135 28686181
     [Google Scholar]
  28. ZhangR. ZhuX. BaiH. NingK. Network pharmacology databases for traditional chinese medicine: Review and assessment.Front. Pharmacol.20191012310.3389/fphar.2019.00123 30846939
     [Google Scholar]
  29. SunS. LiX. RenA. Choline and betaine consumption lowers cancer risk: A meta-analysis of epidemiologic studies.Sci. Rep.2016613554710.1038/srep35547 27759060
     [Google Scholar]
  30. PhiL.T.H. SariI.N. WijayaY.T. Ginsenoside Rd inhibits the metastasis of colorectal cancer via epidermal growth factor receptor signaling axis.IUBMB Life201971560161010.1002/iub.1984 30576064
     [Google Scholar]
  31. TerasakiM. MimaM. KudohS. Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells.Oncol. Rep.201840141442410.3892/or.2018.6398 29693702
     [Google Scholar]
  32. ErtugrulB. IplikE.S. CakmakogluB. In vitro inhibitory effect of succinic acid on T-Cell acute Lymphoblastic leukemia cell lines.Arch. Med. Res.202152327027610.1016/j.arcmed.2020.10.022 33199038
     [Google Scholar]
  33. WatanabeM. MaemuraK. OkiK. ShiraishiN. ShibayamaY. KatsuK. Gamma-aminobutyric acid (GABA) and cell proliferation: Focus on cancer cells.Histol. Histopathol.200621101135114110.14670/HH‑21.1135 16835836
     [Google Scholar]
  34. XuX. LiB. HuangP. Citrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1α signaling.Mol. Med. Rep.2013851379138410.3892/mmr.2013.1702 24064771
     [Google Scholar]
  35. WuX. DaiH. XuC. LiuL. LiS. Citric acid modification of a polymer exhibits antioxidant and anti‐inflammatory properties in stem cells and tissues.J. Biomed. Mater. Res. A2019107112414242410.1002/jbm.a.36748 31180606
     [Google Scholar]
  36. ZhengH. FuX. ShangJ. LuR. OuY. ChenC. Ginsenoside Rg1 protects rat bone marrow mesenchymal stem cells against ischemia induced apoptosis through miR-494-3p and ROCK-1.Eur. J. Pharmacol.201882215416710.1016/j.ejphar.2018.01.001 29307726
     [Google Scholar]
  37. SattariM. IslambulchilarM. AsvadiI. SanaatZ. EsfahaniA. Effect of taurine on attenuating chemotherapy-induced adverse effects in acute lymphoblastic leukemia.J. Cancer Res. Ther.201511242643210.4103/0973‑1482.151933 26148612
     [Google Scholar]
  38. HanJ. XiaJ. ZhangL. Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide.J. Ginseng Res.201943461862410.1016/j.jgr.2018.07.009 31695568
     [Google Scholar]
  39. CaoZ.X. WenY. HeJ.L. Isoliquiritigenin, an orally available natural FLT3 inhibitor from Licorice, exhibits selective anti–acute myeloid leukemia efficacy in vitro and in vivo.Mol. Pharmacol.201996558959910.1124/mol.119.116129 31462456
     [Google Scholar]
  40. KirklandJ.B. Niacin status and treatment-related leukemogenesis.Mol. Cancer Ther.20098472573210.1158/1535‑7163.MCT‑09‑0042 19372544
     [Google Scholar]
  41. Marquez-CurtisL.A. ShirvaikarN. TurnerA.R. Membrane type-1 matrix Metalloproteinase expression in acute Myeloid leukemia and its upregulation by tumor Necrosis factor-α.Cancers (Basel)20124374376210.3390/cancers4030743 24213464
     [Google Scholar]
  42. LiZ.J. ChenZ.X. CenJ.N. HeJ. QiuQ.C. Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells.Chin. Med. J. (Engl.)20131261427312735 23876905
     [Google Scholar]
  43. JahangiriB. Khalaj-KondoriM. AsadollahiE. Purrafee DizajL. SadeghizadehM. MSC-Derived exosomes suppress colorectal cancer cell proliferation and metastasis via miR-100/mTOR/miR-143 pathway.Int. J. Pharm.202262712221410.1016/j.ijpharm.2022.122214 36152993
     [Google Scholar]
  44. ManC.H. ZengX. LamW. Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication.Leukemia20223681990200110.1038/s41375‑022‑01606‑0 35624145
     [Google Scholar]
  45. JiaZ. ZhuH. SunH. Adipose Mesenchymal stem cell-derived Exosomal microRNA-1236 reduces resistance of breast cancer cells to Cisplatin by suppressing SLC9A1 and the Wnt/β-Catenin signaling.Cancer Manag. Res.2020128733874410.2147/CMAR.S270200 33061571
     [Google Scholar]
  46. BonillaX. VanegasN.D.P. VernotJ.P. Acute leukemia induces senescence and impaired Osteogenic differentiation in Mesenchymal stem cells endowing leukemic cells with functional advantages.Stem Cells Int.2019201911610.1155/2019/3864948 31065273
     [Google Scholar]
  47. BuiT.M. WiesolekH.L. SumaginR. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis.J. Leukoc. Biol.2020108378779910.1002/JLB.2MR0220‑549R 32182390
     [Google Scholar]
  48. JamilK. JayaramanA. RaoR. RajuS. In silico evidence of signaling pathways of notch mediated networks in leukemia.Comput. Struct. Biotechnol. J.201212e20120700510.5936/csbj.201207005 24688641
     [Google Scholar]
  49. SharmaM. RossC. SrivastavaS. Ally to adversary: Mesenchymal stem cells and their transformation in leukaemia.Cancer Cell Int.201919113910.1186/s12935‑019‑0855‑5 31139016
     [Google Scholar]
  50. Puerto-CamachoP. Díaz-MartínJ. Olmedo-PelayoJ. Endoglin and MMP14 contribute to ewing sarcoma spreading by modulation of cell–matrix interactions.Int. J. Mol. Sci.20222315865710.3390/ijms23158657 35955799
     [Google Scholar]
  51. YangY. YangY. ShenY. Exploring the pharmacological mechanisms of Shuanghuanglian against T-cell acute lymphoblastic leukaemia through network pharmacology combined with molecular docking and experimental validation.Pharm. Biol.202361125927010.1080/13880209.2023.2168703 36656546
     [Google Scholar]
  52. LiuJ. Exploring the mechanism of physcion-1-O-β-D-monoglucoside against acute lymphoblastic leukaemia based on network pharmacology and experimental validation.Heliyon202393e1400910.1016/j.heliyon.2023.e14009
     [Google Scholar]
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Mechanism of Zhengsui Wan in the Treatment of Acute Lymphoblastic Leukemia Based on Network Pharmacology and Experimental Validation
Curr Stem Cell Res Ther 20, 839 (2025); https://doi.org/10.2174/011574888X327937241129062944
/content/journals/cscr/10.2174/011574888X327937241129062944
/content/journals/cscr/10.2174/011574888X327937241129062944
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  • Article Type:     Research Article
Keyword(s): acute lymphoblastic leukemia; mechanism of action (MoA); molecular docking; molecular dynamics simulation; network pharmacology; ZhengSui Wan

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