Skip to content
2000
Volume 11, Issue 5
  • ISSN: 2215-0838
  • E-ISSN: 2215-0846

Abstract

Background

(L.) Delarbre () has long been used for the treatment of parasitic diseases by the Chinese ethnic minority “Tujia” people residing in the mountainous area of southwestern China.

Objectives

Our previous experiments have demonstrated remarkable pharmacological effects of against (). The present study aimed to investigate the molecular mechanisms underlying the anti-trypanosomiasis activity of .

Methods

Thirty-nine common targets of and trypanosomiasis were obtained from the databases, and these common targets were uploaded to the STRING database to obtain a protein-protein interaction network diagram. Then, the hub genes of these common targets were screened using the CytoHubba. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted by the Metascape. Subsequently, the LeDock was used for molecular docking verification between the hub gene, anti-trypanosomiasis targets, and . Finally, the most effective compound in revealed by the docking results was used for the verification of the anti-trypanosomiasis ability by western blotting analyses.

Results

Enrichment analysis indicated that the anti-trypanosomiasis of was more frequently involved in mediating inflammation, probably by targeting interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-10 (IL-10), and matrix metalloprotein-9 (MMP-9). Molecular docking demonstrated that the bioactive compound quercitrin in exhibited the most stable binding mode with the trypanosomiasis target, and the compound previously confirmed to inhibit , vanicoside F, exhibited the highest stability with ornithine decarboxylase (ODC) and cysteine protease (CYP). The western blotting results showed that quercitrin significantly suppressed lipopolysaccharide (LPS)-induced inflammation (mimicking infection) and decreased expression of IL-10.

Conclusion

Our study demonstrated that acts on the characteristics of multiple targets and pathways with several components through network pharmacology and is thus a potential candidate to be developed as a novel anti-trypanosomiasis drug.

Loading

Article metrics loading...

/content/journals/ctm/10.2174/0122150838286641240415061025
2024-05-03
2026-01-03
Loading full text...

Full text loading...

References

  1. KennedyP.G.E. Update on human African trypanosomiasis (sleeping sickness).J. Neurol.201926692334233710.1007/s00415‑019‑09425‑7 31209574
    [Google Scholar]
  2. BüscherP. CecchiG. JamonneauV. PriottoG. Human African trypanosomiasis.Lancet2017390101102397240910.1016/S0140‑6736(17)31510‑6 28673422
    [Google Scholar]
  3. NokA.J. Arsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis.Parasitol. Res.2003901717910.1007/s00436‑002‑0799‑9 12743807
    [Google Scholar]
  4. BurriC. BrunR. Eflornithine for the treatment of human African trypanosomiasis.Parasitol. Res.200390S1Suppl. 1S49S5210.1007/s00436‑002‑0766‑5 12811548
    [Google Scholar]
  5. FairlambA.H. HornD. Melarsoprol resistance in African Trypanosomiasis.Trends Parasitol.201834648149210.1016/j.pt.2018.04.002 29705579
    [Google Scholar]
  6. SomaniR.R. RaiP.R. KandpileP.S. Ornithine decarboxylase inhibition: A strategy to combat various diseases.Mini Rev. Med. Chem.201818121008102110.2174/1389557517666170927130526 28971766
    [Google Scholar]
  7. LejonV. BentivoglioM. FrancoJ.R. Human African trypanosomiasis.Handb. Clin. Neurol.201311416918110.1016/B978‑0‑444‑53490‑3.00011‑X 23829907
    [Google Scholar]
  8. AyazM. AhmadI. SadiqA. Persicaria hydropiper (L.) Delarbre: A review on traditional uses, bioactive chemical constituents and pharmacological and toxicological activities.J. Ethnopharmacol.202025111251610.1016/j.jep.2019.112516 31884037
    [Google Scholar]
  9. XiaoH. Rao RavuR. TekwaniB.L. Biological evaluation of phytoconstituents from Polygonum hydropiper.Nat. Prod. Res.201731172053205710.1080/14786419.2016.1269094 28000515
    [Google Scholar]
  10. ChongL. Shao-ZhenH. HuaZ. Mechanism prediction of monotropein for the treatment of colorectal cancer by network pharmacology analysis.Digit. Chin. Med.20203111010.1016/j.dcmed.2020.03.001
    [Google Scholar]
  11. OtasekD. MorrisJ.H. BouçasJ. PicoA.R. DemchakB. Cytoscape automation: Empowering workflow-based network analysis.Genome Biol.201920118510.1186/s13059‑019‑1758‑4 31477170
    [Google Scholar]
  12. ZhouY. ZhouB. PacheL. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.Nat. Commun.2019101152310.1038/s41467‑019‑09234‑6 30944313
    [Google Scholar]
  13. ChinC.H. ChenS.H. WuH.H. HoC.W. KoM.T. LinC.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome.BMC Syst. Biol.20148Suppl. 4S1110.1186/1752‑0509‑8‑S4‑S11 25521941
    [Google Scholar]
  14. SterlingT. IrwinJ.J. ZINC 15 – Ligand Discovery for Everyone.J. Chem. Inf. Model.201555112324233710.1021/acs.jcim.5b00559 26479676
    [Google Scholar]
  15. WangZ. SunH. YaoX. Comprehensive evaluation of ten docking programs on a diverse set of protein–ligand complexes: The prediction accuracy of sampling power and scoring power.Phys. Chem. Chem. Phys.20161818129641297510.1039/C6CP01555G 27108770
    [Google Scholar]
  16. RibeiroF.A.P. PontesC. GazzinelliR.T. Therapeutic effects of vaccine derived from amastigote surface protein-2 (ASP-2) against Chagas disease in mouse liver.Cytokine201911328529010.1016/j.cyto.2018.07.017 30037707
    [Google Scholar]
  17. Pérez-MolinaJ.A. MolinaI. Chagas disease.Lancet201839110115829410.1016/S0140‑6736(17)31612‑4 28673423
    [Google Scholar]
  18. KatoC.D. AlibuV.P. NantezaA. MugasaC.M. MatovuE. Interleukin (IL)-6 and IL-10 Are Up Regulated in Late Stage Trypanosoma brucei rhodesiense Sleeping Sickness.PLoS Negl. Trop. Dis.201596e000383510.1371/journal.pntd.0003835 26090964
    [Google Scholar]
  19. WaemaM.W. MainaN.W. NgothoM. IgM, lgG and IL-6 profiles in the Trypanosoma brucei brucei monkey model of human African trypanosomiasis.Acta Trop.2017168454910.1016/j.actatropica.2017.01.012 28099874
    [Google Scholar]
  20. MedeirosN.I. GomesJ.A.S. FiuzaJ.A. MMP-2 and MMP-9 plasma levels are potential biomarkers for indeterminate and cardiac clinical forms progression in chronic Chagas disease.Sci. Rep.2019911417010.1038/s41598‑019‑50791‑z 31578449
    [Google Scholar]
  21. MedeirosN.I. GomesJ.A.S. Correa-OliveiraR. Synergic and antagonistic relationship between MMP ‐2 and MMP ‐9 with fibrosis and inflammation in Chagas’ cardiomyopathy.Parasite Immunol.2017398e1244610.1111/pim.12446 28543409
    [Google Scholar]
  22. MedeirosN.I. FaresR.C.G. FrancoE.P. Differential expression of matrix metalloproteinases 2, 9 and Cytokines by neutrophils and monocytes in the clinical forms of chagas disease.PLoS Negl. Trop. Dis.2017111e000528410.1371/journal.pntd.0005284 28118356
    [Google Scholar]
  23. CurvoE.O.V. FerreiraR.R. MadeiraF.S. Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease.Mem. Inst. Oswaldo Cruz20181134e17044010.1590/0074‑02760170440 29513876
    [Google Scholar]
/content/journals/ctm/10.2174/0122150838286641240415061025
Loading
/content/journals/ctm/10.2174/0122150838286641240415061025
Loading

Data & Media loading...

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