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Volume 31, Issue 7
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286
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Abstract

Objective

This study aimed to preliminary explore the molecular mechanisms of Thunb. (; Saururaceae) in treating non-small cell lung cancer (NSCLC), with the goal of screening drug potential targets for clinical drug development.

Methods

This study employed a multi-omics and multi-source data integration approach to identify potential therapeutic targets of against NSCLC from the TCMSP database, GEO database, BioGPS database, Metascape database, and others. Meanwhile, target localization was performed, and its possible mechanisms of action were predicted. Furthermore, dynamics simulations and molecular docking were used for verification. Multi-omics analysis was used to confirm the selected key genes' efficacy in treating NSCLC.

Results

A total of 31 potential therapeutic targets, 8 key genes, and 5 core components of against NSCLC were screened out. These potential therapeutic targets played a therapeutic role mainly by regulating lipid and atherosclerosis, the TNF signaling pathway, the IL-17 signaling pathway, and others. Molecular docking indicated a stable combination between MMP9 and quercetin. Finally, through multi-omics analysis, it was found that the expression of some key genes was closely related not only to the progression and prognosis of NSCLC but also to the level of immune infiltration.

Conclusion

Through comprehensive network pharmacology and multi-omics analysis, this study predicts that the core components of play a role in treating NSCLC by regulating lipid and atherosclerosis, as well as the TNF signaling pathway. Among them, the anti-NSCLC activity of isoramanone is reported for the first time.

© 2025 Bentham Science Publishers
© 2025 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. ReckM. RabeK.F. Precision diagnosis and treatment for advanced non–small-cell lung cancer.N. Engl. J. Med.2017377984986110.1056/NEJMra170341328854088
     [Google Scholar]
  2. Dela CruzC.S. TanoueL.T. MatthayR.A. Lung cancer: Epidemiology, etiology, and prevention.Clin. Chest Med.201132460564410.1016/j.ccm.2011.09.00122054876
     [Google Scholar]
  3. WoodS.L. PernemalmM. CrosbieP.A. WhettonA.D. The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets.Cancer Treat. Rev.201440455856610.1016/j.ctrv.2013.10.00124176790
     [Google Scholar]
  4. TamuraT. KurishimaK. NakazawaK. Specific organ metastases and survival in metastatic non-small-cell lung cancer.Mol. Clin. Oncol.20153121722110.3892/mco.2014.41025469298
     [Google Scholar]
  5. ChenS. HuangW. LiuZ. Identification of nine mutant genes and establishment of three prediction models of organ tropism metastases of non‐small cell lung cancer.Cancer Med.20231233089310010.1002/cam4.523336161776
     [Google Scholar]
  6. LingC. YueX. LingC. Three advantages of using traditional Chinese medicine to prevent and treat tumor.J. Integr. Med.201412433133510.1016/S2095‑4964(14)60038‑825074882
     [Google Scholar]
  7. DaiK. ChenL. LiuJ. DingY. GuC. LuX. MiR-147a mediated by sodium new houttuyfonate could enhance radiosensitivity of non-small cell lung cancer cells via suppressing STAT3.Adv. Clin. Exp. Med.202130217318110.17219/acem/13059933650331
     [Google Scholar]
  8. ChengB.H. ChanJ.Y.W. ChanB.C.L. Structural characterization and immunomodulatory effect of a polysaccharide HCP-2 from Houttuynia cordata.Carbohydr. Polym.201410324424910.1016/j.carbpol.2013.12.048
     [Google Scholar]
  9. LaldinsangiC. The therapeutic potential of Houttuynia cordata: A current review.Heliyon202288e1038610.1016/j.heliyon.2022.e1038636061012
     [Google Scholar]
  10. QiS. ZhaL. PengY. Quality and metabolomics analysis of Houttuynia cordata based on HS-SPME/GC-MS.Molecules20222712392110.3390/molecules2712392135745045
     [Google Scholar]
  11. WeiP. LuoQ. HouY. ZhaoF. LiF. MengQ. Houttuynia cordata Thunb.: A comprehensive review of traditional applications, phytochemistry, pharmacology and safety.Phytomedicine202412315519510.1016/j.phymed.2023.15519537956635
     [Google Scholar]
  12. ShingnaisuiK. DeyT. MannaP. KalitaJ. Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A review.J. Ethnopharmacol.2018220354310.1016/j.jep.2018.03.03829605674
     [Google Scholar]
  13. ChenY.F. YangJ.S. ChangW.S. TsaiS.C. PengS.F. ZhouY.R. Houttuynia cordata Thunb extract modulates G0/G1 arrest and Fas/CD95-mediated death receptor apoptotic cell death in human lung cancer A549 cells.J. Biomed. Sci.20132011810.1186/1423‑0127‑20‑1823506616
     [Google Scholar]
  14. WuZ. DengX. HuQ. Houttuynia cordata Thunb: An ethnopharmacological review.Front. Pharmacol.20211271469410.3389/fphar.2021.71469434539401
     [Google Scholar]
  15. AdnanM. SiddiquiA.J. AshrafS.A. Network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the molecular targets and potential mechanism of Phoenix dactylifera (Ajwa dates) against candidiasis.Pathogens20231211136910.3390/pathogens1211136938003833
     [Google Scholar]
  16. WangX. WangZ.Y. ZhengJ.H. LiS. TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches.Chin. J. Nat. Med.202119111110.1016/S1875‑5364(21)60001‑833516447
     [Google Scholar]
  17. PinziL. RastelliG. Molecular docking: Shifting paradigms in drug discovery.Int. J. Mol. Sci.20192018433110.3390/ijms2018433131487867
     [Google Scholar]
  18. ZhuD.W. YuQ. SunJ.J. ShenY.H. Evaluating the therapeutic mechanisms of selected active compounds in Houttuynia cordata Thunb. in pulmonary fibrosis via network pharmacology analysis.Front. Pharmacol.20211273361810.3389/fphar.2021.73361834658873
     [Google Scholar]
  19. LaiG.H. WangF. NieD.R. LeiS.J. WuZ.J. CaoJ.X. Identifying active substances and the pharmacological mechanism of Houttuynia cordata Thunb. in treating radiation-induced lung injury based on network pharmacology and molecular docking verification.Evid. Based Complement. Alternat. Med.2022202211310.1155/2022/377634035360660
     [Google Scholar]
  20. BerendsenH.J.C. PostmaJ.P.M. van GunsterenW.F. DiNolaA. HaakJ.R. Molecular dynamics with coupling to an external bath.J. Chem. Phys.19848183684369010.1063/1.448118
     [Google Scholar]
  21. YuanH. LiuL. ZhouJ. ZhangT. DailyJ.W. ParkS. Bioactive components of Houttuynia cordata Thunb and their potential mechanisms against COVID-19 using network pharmacology and molecular docking approaches.J. Med. Food202225435536610.1089/jmf.2021.K.014435438554
     [Google Scholar]
  22. GnanaselvanS YadavSA ManoharanSP Structure-based virtual screening of anti-breast cancer compounds from Artemisia absinthium-insights through molecular docking, pharmacokinetics, and molecular dynamic simulations.J Biomol Struct Dyn20234263267328510.1080/07391102.2023.221280537194295
     [Google Scholar]
  23. PfeiferS.P. From next-generation resequencing reads to a high-quality variant data set.Heredity2017118211112410.1038/hdy.2016.10227759079
     [Google Scholar]
  24. OwzarK. BarryW.T. JungS.H. SohnI. GeorgeS.L. Statistical challenges in preprocessing in microarray experiments in cancer.Clin. Cancer Res.200814195959596610.1158/1078‑0432.CCR‑07‑453218829474
     [Google Scholar]
  25. ChongX. PengR. SunY. ZhangL. ZhangZ. Identification of key genes in gastric cancer by bioinformatics analysis.BioMed Res. Int.2020202011210.1155/2020/765823033015179
     [Google Scholar]
  26. LvS. WangQ. ZhangX. Mechanisms of multi-omics and network pharmacology to explain traditional Chinese medicine for vascular cognitive impairment: A narrative review.Phytomedicine202412315523110.1016/j.phymed.2023.15523138007992
     [Google Scholar]
  27. ZhangW. PengW. LiY. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of aidi injection treating of nonsmall cell lung cancer.Evid. Based Complement. Alternat. Med.2022202211510.1155/2022/835021836523419
     [Google Scholar]
  28. DuH. DingJ. WangP. Anti-respiratory syncytial virus mechanism of Houttuynia cordata Thunb exploration based on network pharmacology.Comb. Chem. High Throughput Screen.20212481137115010.2174/138620732399920091812363132957876
     [Google Scholar]
  29. RuJ. LiP. WangJ. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑1324735618
     [Google Scholar]
  30. LiJ. ZhaoP. LiY. TianY. WangY. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease.Sci. Rep.2015511529010.1038/srep1529026469778
     [Google Scholar]
  31. KimS. ChenJ. ChengT. PubChem 2019 update: Improved access to chemical data.Nucleic Acids Res.201947D1D1102D110910.1093/nar/gky103330371825
     [Google Scholar]
  32. 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/gkz38231106366
     [Google Scholar]
  33. BarrettT. WilhiteS.E. LedouxP. NCBI GEO: Archive for functional genomics data sets-update.Nucleic Acids Res.201341Database issueD991D99523193258
     [Google Scholar]
  34. CloughE. BarrettT. WilhiteS.E. NCBI GEO: Archive for gene expression and epigenomics data sets: 23-year update.Nucleic Acids Res.202452D1D138D14410.1093/nar/gkad96537933855
     [Google Scholar]
  35. WuC. JinX. TsuengG. AfrasiabiC. SuA.I. BioGPS: Building your own mash-up of gene annotations and expression profiles.Nucleic Acids Res.201644D1D313D31610.1093/nar/gkv110426578587
     [Google Scholar]
  36. ZhangX. ZhuJ. YanJ. Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer.Phytomedicine20207915332610.1016/j.phymed.2020.15332632992083
     [Google Scholar]
  37. SzklarczykD. GableA.L. NastouK.C. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.Nucleic Acids Res.202149D1D605D61210.1093/nar/gkaa107433237311
     [Google Scholar]
  38. ShannonP. MarkielA. OzierO. Cytoscape: A software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.123930314597658
     [Google Scholar]
  39. ZhouY. ZhouB. PacheL. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.Nat. Commun.2019101152310.1038/s41467‑019‑09234‑630944313
     [Google Scholar]
  40. TangD. ChenM. HuangX. SRplot: A free online platform for data visualization and graphing.PLoS One20231811e029423610.1371/journal.pone.029423637943830
     [Google Scholar]
  41. JinZ. SatoY. KawashimaM. KanehisaM. KEGG tools for classification and analysis of viral proteins.Protein Sci.20233212e482010.1002/pro.482037881892
     [Google Scholar]
  42. BurleyS.K. BhikadiyaC. BiC. RCSB Protein Data Bank (RCSB.org): Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning.Nucleic Acids Res.202351D1D488D50810.1093/nar/gkac107736420884
     [Google Scholar]
  43. AbrahamM.J. MurtolaT. SchulzR. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers.SoftwareX20151-2C192510.1016/j.softx.2015.06.001
     [Google Scholar]
  44. TangZ. LiC. KangB. GaoG. LiC. ZhangZ. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses.Nucleic Acids Res.201745W1W98W10210.1093/nar/gkx24728407145
     [Google Scholar]
  45. GyőrffyB. Transcriptome‐level discovery of survival‐associated biomarkers and therapy targets in non‐small‐cell lung cancer.Br. J. Pharmacol.2024181336237410.1111/bph.1625737783508
     [Google Scholar]
  46. DigreA. LindskogC. The human protein atlas-spatial localization of the human proteome in health and disease.Protein Sci.202130121823310.1002/pro.398733146890
     [Google Scholar]
  47. UnberathP. KnellC. ProkoschH.U. ChristophJ. Developing new analysis functions for a translational research platform: Extending the cBioPortal for cancer genomics.Stud. Health Technol. Inform.2019258465030942711
     [Google Scholar]
  48. LiT. FanJ. WangB. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells.Cancer Res.20177721e108e11010.1158/0008‑5472.CAN‑17‑030729092952
     [Google Scholar]
  49. LiB. SeversonE. PignonJ.C. Comprehensive analyses of tumor immunity: Implications for cancer immunotherapy.Genome Biol.201617117410.1186/s13059‑016‑1028‑727549193
     [Google Scholar]
  50. HanK JinC ChenH WangP YuM DingK. Structural characterization and anti-A549 lung cancer cells bioactivity of a polysaccharide from Houttuynia cordata.Int. J. Biol. Macromol.2018120PT A28829610.1016/j.ijbiomac.2018.08.06130114425
     [Google Scholar]
  51. LingL. LuY. ZhangY. Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of influenza virus and Toll-like receptor signalling.Phytomedicine20206715315010.1016/j.phymed.2019.15315031958713
     [Google Scholar]
  52. RafiqS. HaoH. IjazM. RazaA. Pharmacological effects of Houttuynia cordata Thunb (H. cordata): A comprehensive review.Pharmaceuticals (Basel)2022159107910.3390/ph1509107936145299
     [Google Scholar]
  53. ChiowK.H. PhoonM.C. PuttiT. TanB.K.H. ChowV.T. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection.Asian Pac. J. Trop. Med.2016911710.1016/j.apjtm.2015.12.00226851778
     [Google Scholar]
  54. YangL. JiW. ZhongH. WangL. ZhuX. ZhuJ. Anti-tumor effect of volatile oil from Houttuynia cordata Thunb. on HepG2 cells and HepG2 tumor-bearing mice.RSC Advances2019954315173152610.1039/C9RA06024C35527944
     [Google Scholar]
  55. WangY-H. ZhouH-Y. MaJ-Y. Investigating the mechanism of Qu Du Qiang Fei 1 Hao Fang formula against coronavirus disease 2019 based on network pharmacology method.World J. Tradit. Chin. Med.2024109310310.4103/2311‑8571.395061
     [Google Scholar]
  56. Reyes-FariasM. Carrasco-PozoC. The anti-cancer effect of quercetin: Molecular implications in cancer metabolism.Int. J. Mol. Sci.20192013317710.3390/ijms2013317731261749
     [Google Scholar]
  57. GuoH. DingH. TangX. Quercetin induces pro-apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro.Thorac. Cancer20211291415142210.1111/1759‑7714.1392533709560
     [Google Scholar]
  58. ChangJ.H. LaiS.L. ChenW.S. Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways.Biochim. Biophys. Acta Mol. Cell Res.20171864101746175810.1016/j.bbamcr.2017.06.01728648644
     [Google Scholar]
  59. LuoQ. SongY. KangJ. RETRACTED: mtROS-mediated Akt/AMPK/mTOR pathway was involved in copper-induced autophagy and it attenuates copper-induced apoptosis in RAW264.7 mouse monocytes.Redox Biol.20214110191210.1016/j.redox.2021.10191233706171
     [Google Scholar]
  60. YuanM. TuB. LiH. Cancer-associated fibroblasts employ NUFIP1-dependent autophagy to secrete nucleosides and support pancreatic tumor growth.Nat. Cancer20223894596010.1038/s43018‑022‑00426‑635982178
     [Google Scholar]
  61. ImranM. SalehiB. Sharifi-RadJ. Kaempferol: A key emphasis to its anticancer potential.Molecules20192412227710.3390/molecules2412227731248102
     [Google Scholar]
  62. LiC. ZhaoY. YangD. Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.Biochem. Cell Biol.2015931162710.1139/bcb‑2014‑006725453494
     [Google Scholar]
  63. ChenJ. WangW. ShiC. FangJ. A comparative study of sodium houttuyfonate and 2-undecanone for their in vitro and in vivo anti-inflammatory activities and stabilities.Int. J. Mol. Sci.20141512229782299410.3390/ijms15122297825514406
     [Google Scholar]
  64. LouY. GuoZ. ZhuY. Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway.J. Exp. Clin. Cancer Res.201938124210.1186/s13046‑019‑1255‑331174565
     [Google Scholar]
  65. ZouY. ZhangX. ChenX. HuY. YingK. WangP. Optimization of volatile markers of lung cancer to exclude interferences of non-malignant disease.Cancer Biomark.201414537137910.3233/CBM‑14041825171479
     [Google Scholar]
  66. MarienE. MeisterM. MuleyT. Non‐small cell lung cancer is characterized by dramatic changes in phospholipid profiles.Int. J. Cancer201513771539154810.1002/ijc.2951725784292
     [Google Scholar]
  67. ZhangT. BaiR. WangQ. Fluvastatin inhibits HMG-CoA reductase and prevents non-small cell lung carcinogenesis.Cancer Prev. Res. (Phila.)2019121283784810.1158/1940‑6207.CAPR‑19‑021131554629
     [Google Scholar]
  68. LiangL. HeH. JiangS. TIAM2 contributes to osimertinib resistance, cell motility, and tumor-associated macrophage M2-like polarization in lung adenocarcinoma.Int. J. Mol. Sci.202223181041510.3390/ijms23181041536142328
     [Google Scholar]
  69. NguyenP.A. ChangC.C. GalvinC.J. Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A cancer registry cohort study in Taiwan.Cancer Sci.202011182965297310.1111/cas.1449332441434
     [Google Scholar]
  70. ShangG.S. LiuL. QinY.W. IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition.Oncol. Lett.20171364657466010.3892/ol.2017.604828599466
     [Google Scholar]
  71. YanF. DuR. WeiF. Expression of TNFR2 by regulatory T cells in peripheral blood is correlated with clinical pathology of lung cancer patients.Cancer Immunol. Immunother.201564111475148510.1007/s00262‑015‑1751‑z26280204
     [Google Scholar]
  72. ZhangY.W. ChenQ.Q. CaoJ. Expression of tumor necrosis factor receptor 2 in human non‐small cell lung cancer and its role as a potential prognostic biomarker.Thorac. Cancer201910343744410.1111/1759‑7714.1294830628200
     [Google Scholar]
  73. MaX. SongY. ZhangK. Recombinant mutated human TNF in combination with chemotherapy for stage IIIB/IV non-small cell lung cancer: A randomized, phase III study.Sci. Rep.201551991810.1038/srep0991825897826
     [Google Scholar]
  74. HuangH. Matrix Metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances.Sensors (Basel)20181810324910.3390/s1810324930262739
     [Google Scholar]
  75. GeW. GongY. LiY. IL‐17 induces non‐small cell lung cancer metastasis via GCN5‐dependent SOX4 acetylation enhancing MMP9 gene transcription and expression.Mol. Carcinog.20236291399141610.1002/mc.2358537294072
     [Google Scholar]
  76. SongH. TianZ. QinY. YaoG. FuS. GengJ. Astrocyte elevated gene-1 activates MMP9 to increase invasiveness of colorectal cancer.Tumour Biol.20143576679668510.1007/s13277‑014‑1883‑324705862
     [Google Scholar]
  77. WangF. XiaoW. SunJ. HanD. ZhuY. MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma.Tumour Biol.20143598653865810.1007/s13277‑014‑2131‑624867100
     [Google Scholar]
  78. ChenW. ZhangY. FangZ. QiW. XuY. TRIM66 hastens the malignant progression of non-small cell lung cancer via modulating MMP9-mediated TGF-β/SMAD pathway.Cytokine202215315583110.1016/j.cyto.2022.15583135301175
     [Google Scholar]
  79. HwangK.E. KimH.J. SongI.S. Salinomycin suppresses TGF-β1-induced EMT by down-regulating MMP-2 and MMP-9 via the AMPK/SIRT1 pathway in non-small cell lung cancer.Int. J. Med. Sci.202118371572610.7150/ijms.5008033437206
     [Google Scholar]
  80. RodriguesR.M. HeY. HwangS. E-selectin-dependent inflammation and lipolysis in adipose tissue exacerbate steatosis-to-NASH progression via S100A8/9.Cell. Mol. Gastroenterol. Hepatol.202213115117110.1016/j.jcmgh.2021.08.00234390865
     [Google Scholar]
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Unraveling the Core Components and Critical Targets of Houttuynia cordata Thunb. in Treating Non-small Cell Lung Cancer through Network Pharmacology and Multi-omics Analysis
Curr. Pharm. Des. 31, 540 (2025); https://doi.org/10.2174/0113816128330427241017110325
/content/journals/cpd/10.2174/0113816128330427241017110325
/content/journals/cpd/10.2174/0113816128330427241017110325
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  • Article Type:     Research Article
Keyword(s): drug targets; Houttuynia cordata Thunb.; molecular docking; molecular dynamics simulation; network pharmacology; non-small cell lung cancer

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