Skip to content
2000
Volume 28, Issue 15
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Objective

Chemotherapy-induced phlebitis (CIP) is a side product of chemotherapy treatment for malignant tumors, which affects the therapeutic effect and quality of life of cancer patients, and still lacks a clear therapeutic means. In this study, we investigated the therapeutic effects of QLTMP on CIP using network pharmacology and verified the anti-inflammatory mechanism of QLTMP in a mice model induced by vinorelbine.

Methods

Network pharmacology analysis was performed to identify bioactive compounds in QLTMP. The protein-protein interaction network was used to identify the core therapeutic targets of QLTMP against CIP, analyze biological function and pathway enrichment based on the identified core therapeutic targets, and evaluate the therapeutic effect of QLTMP in a model of CIP induced by vinorelbine to confirm the reliability of the network pharmacological analysis.

One hundred and sixty-five bioactive compounds of QLTMP matched the screening criteria and identified 19 core therapeutic targets of QLTMP against CIP. Biofunctional analysis showed that the therapeutic effect of QLTMP on CIP was mainly related to the inhibition of inflammation, while pathway enrichment analysis showed that the TNF signaling pathway was involved in the inflammatory process.

Results

Experimental confirmation in a mice model showed that QLTMP exerts anti-inflammatory effects through modulation of the PI3K/AKT/TNF signaling pathway, a discovery consistent with the network pharmacological analysis.

Discussion and Conclusion

The network pharmacological analysis of the anti-inflammatory mechanism of QLTMP on CIP and its exploration of experiments provide a theoretical basis for the design of agents that can mitigate or cure CIP.

Loading

Article metrics loading...

/content/journals/cchts/10.2174/1386207325666220629121318
2025-02-10
2026-01-02
Loading full text...

Full text loading...

References

  1. WuG. WuL. ZhouH. LinM. PengL. WangY. ZhaiY. HuX. ZhengY. LvD. LiuJ. ShentuJ. A phase i comparative pharmacokinetic and safety study of two intravenous formulations of vinorelbine in patients with advanced non-small cell lung cancer.Front. Pharmacol.20191077410.3389/fphar.2019.00774 31354489
    [Google Scholar]
  2. HarrisV. HughesM. RobertsR. DolanG. WilliamsE.M. The development and testing of a Chemotherapy-Induced Phlebitis Severity (CIPS) scale for patients receiving anthracycline chemotherapy for breast cancer.J. Clin. Med.202093E70110.3390/jcm9030701 32150833
    [Google Scholar]
  3. HeZ. ZhangY. KhanA.R. JiJ. YuA. ZhaiG. A novel progress of drug delivery system for organelle targeting in tumour cells.J. Drug Target.2021291122810.1080/1061186X.2020.1797051 32698651
    [Google Scholar]
  4. HoK.H. CheungD.S. Guidelines on timing in replacing peripheral intravenous catheters.J. Clin. Nurs.20122111-121499150610.1111/j.1365‑2702.2011.03974.x 22340078
    [Google Scholar]
  5. YamadaT. EgashiraN. WatanabeH. NagataK. YanoT. NonakaT. OishiR. Decrease in the vinorelbine-induced venous irritation by pharmaceutical intervention.Support. Care Cancer20122071549155310.1007/s00520‑011‑1244‑3 21805382
    [Google Scholar]
  6. VillaG. ChelazziC. GiuaR. TofaniL. ZagliG. BoninsegniP. PinelliF. De GaudioA.R. RomagnoliS. In-line filtration reduces postoperative venous peripheral phlebitis associated with cannulation: A randomized clinical trial.Anesth. Analg.201812761367137410.1213/ANE.0000000000003393 29697508
    [Google Scholar]
  7. RamosJ.G. LeavittA.D. RosensteinM.G. Phlebitis after intravenous iron sucrose administration in postpartum women.Obstet. Gynecol.2020136116716910.1097/AOG.0000000000003934 32541278
    [Google Scholar]
  8. BrijsJ. Van EldereA. BreynaertC. SchrijversR. Transient phlebitis after propofol infusion: A mimic of hypersensitivity.J. Allergy Clin. Immunol. Pract.20208133033110.1016/j.jaip.2019.08.037 31585795
    [Google Scholar]
  9. Bigdeli ShamlooM.B. NasiriM. ManeiyM. DorchinM. MojabF. BahramiH. NaseriM.S. KiarsiM. Effects of topical sesame (Sesamum indicum) oil on the pain severity of chemotherapy-induced phlebitis in patients with colorectal cancer: A randomized controlled trial.Complement. Ther. Clin. Pract.201935788510.1016/j.ctcp.2019.01.016 31003690
    [Google Scholar]
  10. LuoT.T. LuY. YanS.K. XiaoX. RongX.L. GuoJ. Network pharmacology in research of Chinese medicine formula: Methodology, application and prospective.Chin. J. Integr. Med.2020261728010.1007/s11655‑019‑3064‑0 30941682
    [Google Scholar]
  11. YuanH. MaQ. CuiH. LiuG. ZhaoX. LiW. PiaoG. How can synergism of traditional medicines benefit from network pharmacology?Molecules2017227E113510.3390/molecules22071135 28686181
    [Google Scholar]
  12. ZhangY-F. HuangY. NiY-H. XuZ-M. Systematic elucidation of the mechanism of geraniol via network pharmacology.Drug Des. Devel. Ther.2019131069107510.2147/DDDT.S189088 31040644
    [Google Scholar]
  13. XuH.Y. ZhangY.Q. LiuZ.M. ChenT. LvC.Y. TangS.H. ZhangX.B. ZhangW. LiZ.Y. ZhouR.R. YangH.J. WangX.J. HuangL.Q. ETCM: An encyclopaedia of traditional Chinese medicine.Nucleic Acids Res.201947D1D976D98210.1093/nar/gky987 30365030
    [Google Scholar]
  14. WeiM. LiH. LiQ. QiaoY. MaQ. XieR. WangR. LiuY. WeiC. LiB. ZhengC. SunB. YuB. Based on network pharmacology to explore the molecular targets and mechanisms of gegen qinlian decoction for the treatment of ulcerative colitis.BioMed Res. Int.20202020521740510.1155/2020/5217405 33299870
    [Google Scholar]
  15. LiuT.H. ChenW.H. ChenX.D. LiangQ.E. TaoW.C. JinZ. XiaoY. ChenL.G. Network pharmacology identifies the mechanisms of action of taohongsiwu decoction against essential hypertension.Med. Sci. Monit.202026e92068210.12659/MSM.920682 32187175
    [Google Scholar]
  16. StensonP.D. MortM. BallE.V. EvansK. HaydenM. HeywoodS. HussainM. PhillipsA.D. CooperD.N. The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies.Hum. Genet.2017136666567710.1007/s00439‑017‑1779‑6 28349240
    [Google Scholar]
  17. TaoQ. DuJ. LiX. ZengJ. TanB. XuJ. LinW. ChenX.L. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.Drug Dev. Ind. Pharm.20204681345135310.1080/03639045.2020.1788070 32643448
    [Google Scholar]
  18. SzklarczykD. GableA.L. NastouK.C. LyonD. KirschR. PyysaloS. DonchevaN.T. LegeayM. FangT. BorkP. JensenL.J. von MeringC. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.Nucleic Acids Res.202149D1D605D61210.1093/nar/gkaa1074 33237311
    [Google Scholar]
  19. ReimandJ. IsserlinR. VoisinV. KuceraM. Tannus-LopesC. RostamianfarA. WadiL. MeyerM. WongJ. XuC. MericoD. BaderG.D. Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap.Nat. Protoc.201914248251710.1038/s41596‑018‑0103‑9 30664679
    [Google Scholar]
  20. FoutchD. PhamB. ShenT. Protein conformational switch discerned via network centrality properties.Comput. Struct. Biotechnol. J.2021193599360810.1016/j.csbj.2021.06.004 34257839
    [Google Scholar]
  21. The gene ontology resource: 20 years and still going strong.Nucleic Acids Res.201947D1D330D33810.1093/nar/gky1055 30395331
    [Google Scholar]
  22. KanehisaM. SatoY. FurumichiM. MorishimaK. TanabeM. New approach for understanding genome variations in KEGG.Nucleic Acids Res.201947D1D590D59510.1093/nar/gky962 30321428
    [Google Scholar]
  23. CongL. ZhuY. TuG. A bioinformatic analysis of microRNAs role in osteoarthritis.Osteoarthritis Cartilage20172581362137110.1016/j.joca.2017.03.012 28336453
    [Google Scholar]
  24. YamadaT. Pharmacological study and pharmaceutical intervention to reduce intravenous injection-induced vascular injury.Yakugaku Zasshi2015135346547210.1248/yakushi.14‑00161 25759054
    [Google Scholar]
  25. WangZ. MaL. WangX. CaiH. HuangJ. LiuJ. HuJ. SuD. Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.Cancer Chemother. Pharmacol.201474223924710.1007/s00280‑014‑2487‑8 24879290
    [Google Scholar]
  26. GeG.F. ShiW.W. YuC.H. JinX.Y. ZhangH.H. ZhangW.Y. WangL.C. YuB. Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits.Toxicol. Appl. Pharmacol.2017318233210.1016/j.taap.2017.01.013 28126410
    [Google Scholar]
  27. KimN.H. JeonS. LeeH.J. LeeA.Y. Impaired PI3K/Akt activation-mediated NF-kappaB inactivation under elevated TNF-alpha is more vulnerable to apoptosis in vitiliginous keratinocytes.J. Invest. Dermatol.2007127112612261710.1038/sj.jid.5700900 17522703
    [Google Scholar]
  28. LiuS. CaoC. ZhangY. LiuG. RenW. YeY. SunT. PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis.J. Orthop. Surg. Res.201914142510.1186/s13018‑019‑1394‑4 31829201
    [Google Scholar]
  29. DeviK.P. MalarD.S. NabaviS.F. SuredaA. XiaoJ. NabaviS.M. DagliaM. Kaempferol and inflammation: From chemistry to medicine.Pharmacol. Res.20159911010.1016/j.phrs.2015.05.002 25982933
    [Google Scholar]
  30. RajendranP. RengarajanT. NandakumarN. PalaniswamiR. NishigakiY. NishigakiI. Kaempferol, a potential cytostatic and cure for inflammatory disorders.Eur. J. Med. Chem.20148610311210.1016/j.ejmech.2014.08.011 25147152
    [Google Scholar]
  31. NamS.Y. JeongH.J. KimH.M. Kaempferol impedes IL-32-induced monocyte-macrophage differentiation.Chem. Biol. Interact.201727410711510.1016/j.cbi.2017.07.010 28711657
    [Google Scholar]
  32. TangX.L. LiuJ.X. DongW. LiP. LiL. HouJ.C. ZhengY.Q. LinC.R. RenJ.G. Protective effect of kaempferol on LPS plus ATP-induced inflammatory response in cardiac fibroblasts.Inflammation20153819410110.1007/s10753‑014‑0011‑2 25189464
    [Google Scholar]
  33. BianY. LeiJ. ZhongJ. WangB. WanY. LiJ. LiaoC. HeY. LiuZ. ItoK. ZhangB. Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice.J. Nutr. Biochem.20229910884010.1016/j.jnutbio.2021.108840 34419569
    [Google Scholar]
  34. HuY. GuiZ. ZhouY. XiaL. LinK. XuY. Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages.Free Radic. Biol. Med.201914514616010.1016/j.freeradbiomed.2019.09.024 31550528
    [Google Scholar]
  35. HuK. MiaoL. GoodwinT.J. LiJ. LiuQ. HuangL. Quercetin remodels the tumor microenvironment to improve the permeation, retention, and antitumor effects of nanoparticles.ACS Nano20171154916492510.1021/acsnano.7b01522 28414916
    [Google Scholar]
  36. ZingalesV. Sirerol-PiquerM.S. Fernández-FranzónM. RuizM.J. Role of quercetin on sterigmatocystin-induced oxidative stress-mediated toxicity.Food Chem. Toxicol.202115611249810.1016/j.fct.2021.112498 34380011
    [Google Scholar]
  37. KimD.H. KhanH. UllahH. HassanS.T.S. ŠmejkalK. EfferthT. MahomoodallyM.F. XuS. HabtemariamS. FilosaR. LagoaR. RengasamyK.R. MicroRNA targeting by quercetin in cancer treatment and chemoprotection.Pharmacol. Res.201914710434610.1016/j.phrs.2019.104346 31295570
    [Google Scholar]
  38. ZhouB.X. LiJ. LiangX.L. PanX.P. HaoY.B. XieP.F. JiangH.M. YangZ.F. ZhongN.S. β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.Acta Pharmacol. Sin.20204191178119610.1038/s41401‑020‑0403‑9 32504068
    [Google Scholar]
  39. GongG. GuanY.Y. ZhangZ.L. RahmanK. WangS.J. ZhouS. LuanX. ZhangH. Isorhamnetin: A review of pharmacological effects.Biomed. Pharmacother.202012811030110.1016/j.biopha.2020.110301 32502837
    [Google Scholar]
  40. KasirzadehS. GhahremaniM.H. SetayeshN. JeivadF. ShadboorestanA. TaheriA. Beh-PajoohA. Azadkhah ShalmaniA. Ebadollahi-NatanziA. KhanA. SabzevariS. SabzevariO. β-sitosterol alters the inflammatory response in CLP rat model of sepsis by modulation of NFκB signaling.BioMed Res. Int.20212021553556210.1155/2021/5535562 33997001
    [Google Scholar]
  41. TianX. PengX. LinJ. ZhangY. ZhanL. YinJ. ZhangR. ZhaoG. Isorhamnetin ameliorates aspergillus fumigatus keratitis by reducing fungal load, inhibiting pattern-recognition receptors and inflammatory cytokines.Invest. Ophthalmol. Vis. Sci.20216233810.1167/iovs.62.3.38 33783487
    [Google Scholar]
  42. WangJ.L. QuanQ. JiR. GuoX.Y. ZhangJ.M. LiX. LiuY.G. Isorhamnetin suppresses PANC-1 pancreatic cancer cell proliferation through S phase arrest.Biomed. Pharmacother.201810892593310.1016/j.biopha.2018.09.105 30372904
    [Google Scholar]
  43. HuJ. ZhangY. JiangX. ZhangH. GaoZ. LiY. FuR. LiL. LiJ. CuiH. GaoN. ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine.J. Exp. Clin. Cancer Res.201938122510.1186/s13046‑019‑1201‑4 31138329
    [Google Scholar]
  44. NotasG. PanagiotopoulosA. VamvoukakiR. KalyvianakiK. KiagiadakiF. DeliA. KampaM. CastanasE. ERα36-GPER1 collaboration inhibits TLR4/NFκB-induced pro-inflammatory activity in breast cancer cells.Int. J. Mol. Sci.20212214760310.3390/ijms22147603 34299224
    [Google Scholar]
  45. MitobeY. IkedaK. SuzukiT. TakagiK. KawabataH. Horie-InoueK. InoueS. ESR1-stabilizing long noncoding RNA TMPO-AS1 promotes hormone-refractory breast cancer progression.Mol. Cell. Biol.20193923e00261e1910.1128/MCB.00261‑19 31501276
    [Google Scholar]
  46. MitobeY. IinoK. TakayamaK.I. IkedaK. SuzukiT. AogiK. KawabataH. SuzukiY. Horie-InoueK. InoueS. PSF promotes ER-positive breast cancer progression via posttranscriptional regulation of ESR1 and SCFD2.Cancer Res.202080112230224210.1158/0008‑5472.CAN‑19‑3095 32213542
    [Google Scholar]
  47. ReinertT. GonçalvesR. BinesJ. Implications of ESR1 mutations in hormone receptor-positive breast cancer.Curr. Treat. Options Oncol.20181952410.1007/s11864‑018‑0542‑0 29666928
    [Google Scholar]
  48. KangH. LeeY. KimM.B. HuS. JangH. ParkY.K. LeeJ.Y. The loss of histone deacetylase 4 in macrophages exacerbates hepatic and adipose tissue inflammation in male but not in female mice with diet-induced non-alcoholic steatohepatitis.J. Pathol.2021255331932910.1002/path.5758 34374436
    [Google Scholar]
  49. LouT. HuangQ. SuH. ZhaoD. LiX. Targeting Sirtuin 1 signaling pathway by ginsenosides.J. Ethnopharmacol.202126811365710.1016/j.jep.2020.113657 33276056
    [Google Scholar]
  50. LiuT. LiangX. SunY. YangS. Rapamycin suppresses the PI3K/AKT/mTOR signaling pathway by targeting SIRT1 in esophageal cancer.Exp. Ther. Med.2021224119010.3892/etm.2021.10624 34475980
    [Google Scholar]
  51. PillaiV.B. SundaresanN.R. GuptaM.P. Regulation of Akt signaling by sirtuins: Its implication in cardiac hypertrophy and aging.Circ. Res.2014114236837810.1161/CIRCRESAHA.113.300536 24436432
    [Google Scholar]
  52. ZhuX. LiuQ. WangM. LiangM. YangX. XuX. ZouH. QiuJ. Activation of Sirt1 by resveratrol inhibits TNF-α induced inflammation in fibroblasts.PLoS One2011611e2708110.1371/journal.pone.0027081 22069489
    [Google Scholar]
  53. MartinsJ. Nutrition therapy regulates caffeine metabolism with relevance to NAFLD and induction of type 3 diabetes.Diabet. Metabol. Disorders2017411910.24966/DMD‑201X/100019
    [Google Scholar]
  54. MartinsI.J. Anti-aging genes improve appetite regulation and reverse cell senescence and apoptosis in global populations.Adv. Aging Res.2016050192610.4236/aar.2016.51002
    [Google Scholar]
  55. MartinsI.J. Single gene inactivation with implications to diabetes and multiple organ dysfunction syndrome.J. Clin. Epigenet.2017030310.21767/2472‑1158.100058
    [Google Scholar]
  56. IsideC. ScafuroM. NebbiosoA. AltucciL. SIRT1 activation by natural phytochemicals: An overview.Front. Pharmacol.202011122510.3389/fphar.2020.01225 32848804
    [Google Scholar]
  57. LiS. LiY. WuZ. WuZ. FangH. Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound.Am. J. Physiol. Endocrinol. Metab.20213214E509E52010.1152/ajpendo.00042.2021 34423682
    [Google Scholar]
  58. TangZ.L. ZhangK. LvS.C. XuG.W. ZhangJ.F. JiaH.Y. LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice.Cytokine202114815565710.1016/j.cyto.2021.155657 34425525
    [Google Scholar]
/content/journals/cchts/10.2174/1386207325666220629121318
Loading
/content/journals/cchts/10.2174/1386207325666220629121318
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test