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2000
Volume 24, Issue 3
  • ISSN: 1871-5230
  • E-ISSN: 1875-614X

Abstract

Introduction

(Miller) Urb, popularly known as “marupazinho”, is frequently used in traditional medicine for treating various diseases, including hypertension, ulcers, constipation, and intestinal infection. However, there is little scientific knowledge available regarding the pharmacological effects of this species. Thus and phytochemical studies are required to establish whether this plant has these effects. Further tests were necessary to evaluate the pharmacological activity of the compounds found in this plant, and demonstrate results related to the anti-inflammatory process, which will serve as the basis for future research in this area.

Methods

Therefore, our study aimed to determine the acute toxicity levels of the hexanoic fraction of the ethanolic extract of (referred to as ExtHF) using adult zebrafish, with the determination of the LD, behavioral and histopathological evaluations, as well as the anti-inflammatory potential of ExtHF, at different doses, in abdominal edema induced by carrageenan. The acute toxicity study and histopathological analysis in zebrafish showed that ExtHF has a high toxic potential, with an LD of 346.74 mg/kg. However, ExtHF showed an anti-inflammatory effect by inhibiting abdominal edema at all doses tested.

Results

The inhibition rate of 66.2% and 62.4%, respectively, was observed with the 2.5 mg/kg dose, respectively, indicating that ExtHF is safe in terms of acute toxicity based on behavioral changes, mortality rate, and histopathological examination. Therefore, ExtHF has an acceptable level of safety for acute toxicity, defined by the analysis of behavioral changes, mortality, and histopathology, showing a significant anti-inflammatory effect in zebrafish at all doses, showing that ExtHF was very efficient in preventing the formation of edema, in addition, it was also revealed that ExtHF has a great effect in reversing the edema which is already installed.

Conclusion

Molecular docking studies revealed that the eleutherol molecule isolated from has a dual inhibition profile against cyclooxygenase-1 and 2.

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2024-12-27
2025-11-14

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References

  1. K, M.K.; Nair, B.R. Isolation of isoeleutherol from microwave assisted methanol extract of Eleutherine bulbosa bulbs, its crystal structure elucidation and cytotoxicity evaluation.J. Mol. Struct.2022124713137610.1016/j.molstruc.2021.131376
     [Google Scholar]
  2. ArbainD. SriwahyuniK. SusantiD. TaherM. Genus Eleutherine: A review of its distribution, traditional uses, phytochemistry, biological activities and its interchangeable common names.S. Afr. J. Bot.202215073174310.1016/j.sajb.2022.08.022
     [Google Scholar]
  3. DamascenoR.G.L. GilA.S.B. Flora das cangas da Serra dos Carajás, Pará, Brasil: Iridaceae.Rodriguésia2016675spe1373137610.1590/2175‑7860201667534
     [Google Scholar]
  4. ShinkaiV.M.T. SampaioI.M.O. dos SantosE.G. Galué-ParraA.J. FerreiraD.P. BalizaD.D.M.S. RamosN.F. PimentaR.S. BurbanoR.M.R. SenaC.B.C. MacchiB.M. FerreiraI.M. SilvaE.O. do NascimentoJ.L.M. In vitro cytotoxic effects and mechanisms of action of eleutherine isolated from Eleutherine plicata bulb in rat glioma C6 cells.Molecules20222724885010.3390/molecules27248850 36557983
     [Google Scholar]
  5. SutapaH. WidodoM.A. PurnomoB.B. SoebadiD.M. NegaraE.P. In silico and in vitro study: COX-2 inhibition by ethanol extract of dayak onion bulb (Eleutherine americana merr) as treatment innovation of Benign Prostatic Hyperplasia (BPH).Antiinflamm. Antiallergy Agents Med. Chem.2021201687410.2174/1871523019666200304121702 32129166
     [Google Scholar]
  6. VillegasL.F. FernándezI.D. MaldonadoH. TorresR. ZavaletaA. VaisbergA.J. HammondG.B. Evaluation of the wound-healing activity of selected traditional medicinal plants from Perú.J. Ethnopharmacol.199755319320010.1016/S0378‑8741(96)01500‑0 9080340
     [Google Scholar]
  7. KusumaI.W. ArungE.T. RosamahE. PurwatiningsihS. KuspradiniH. Syafrizal AstutiJ. KimY.U. ShimizuK. Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia.J. Nat. Med.201064222322610.1007/s11418‑010‑0396‑7 20155402
     [Google Scholar]
  8. AmeliaT. PratiwiD. TjahjonoD.H. In silico study of the component of Eleutherine americana MERR. on human estrogen reseptor alpha as potential anti-breast cancer.Int. Conf. Comput. Sci. Technol.20151910.2991/iccst‑15.2015.2
     [Google Scholar]
  9. LestariD. KartikaR. MarlianaE. Antioxidant and anticancer activity of Eleutherine bulbosa (Mill.) Urb on leukemia cells L 1210.J. Phys. Conf. Ser.20191277101202210.1088/1742‑6596/1277/1/012022
     [Google Scholar]
  10. EtienneR. Pereira Dias ViegasF. ViegasC.Jr Pathophysiological aspects of inflammation and drug design: An updated overview.Revista Virtual de Química202113116719110.21577/1984‑6835.20200138
     [Google Scholar]
  11. KainV. PrabhuS.D. HaladeG.V. Inflammation revisited: Inflammation versus resolution of inflammation following myocardial infarction.Basic Res. Cardiol.2014109644410.1007/s00395‑014‑0444‑7 25248433
     [Google Scholar]
  12. MerleN.S. ChurchS.E. Fremeaux-BacchiV. RoumeninaL.T. Complement system part I - molecular mechanisms of activation and regulation.Front. Immunol.2015626210.3389/fimmu.2015.00262 26082779
     [Google Scholar]
  13. Quitian-UsecheY.F. Sánchez-OrtizB.L. BorgesS.F. RamosB. de SouzaG.C. BatistaM.A. da Silva Hage MelimL.I. FerreiraI.M. CarvalhoJ.C.T. BorgesR.S. Fatty ethanolamide of Bertholletia excelsa triglycerides (Brazil nuts): Anti-inflammatory action and acute toxicity evaluation in Zebrafish (Danio rerio).Inflammopharmacology20212951519153710.1007/s10787‑021‑00867‑y 34498144
     [Google Scholar]
  14. HolandaF.H. RibeiroA.N. Sánchez-OrtizB.L. de SouzaG.C. BorgesS.F. FerreiraA.M. FlorentinoA.C. YoshiokaS.A. MoraesL.S. CarvalhoJ.C.T. FerreiraI.M. Anti-inflammatory potential of baicalein combined with silk fibroin protein in a zebrafish model (Danio rerio).Biotechnol. Lett.202345223525310.1007/s10529‑022‑03334‑y 36550336
     [Google Scholar]
  15. FerreiraA.M. de SouzaA.A. KogaR.C.R. SenaI.S. MatosM.J.S. TomaziR. FerreiraI.M. CarvalhoJ.C.T. Anti-melanogenic potential of natural and synthetic substances: Application in Zebrafish Model.Molecules2023283105310.3390/molecules28031053 36770722
     [Google Scholar]
  16. de SouzaA.A. OrtízB.L.S. BorgesS.F. PintoA.V.P. RamosR.S. PenaI.C. KogaR.C. BatistaC.E. SouzaG.C. FerreiraA.M. JuniorS. CarvalhoJ.C. Acute toxicity and anti-inflammatory activity of Trattinnickia rhoifolia willd (sucuruba) using the zebrafish Model.Molecules20222722774110.3390/molecules27227741 36431841
     [Google Scholar]
  17. HuangS.Y. FengC.W. HungH.C. ChakrabortyC. ChenC.H. ChenW.F. JeanY.H. WangH.M.D. SungC.S. SunY.M. WuC.Y. LiuW. HsiaoC.D. WenZ.H. A novel zebrafish model to provide mechanistic insights into the inflammatory events in carrageenan-induced abdominal edema.PLoS One201498e10441410.1371/journal.pone.0104414 25141004
     [Google Scholar]
  18. CarvalhoJ.C.T. KeitaH. SantanaG.R. de SouzaG.C. dos SantosI.V.F. AmadoJ.R.R. KouroumaA. PradaA.L. de Oliveira CarvalhoH. SilvaM.L. Effects of Bothrops alternatus venom in zebrafish: A histopathological study.Inflammopharmacology201826127328410.1007/s10787‑017‑0362‑z 28516375
     [Google Scholar]
  19. BorgesR.S. KeitaH. OrtizB.L.S. dos Santos SampaioT.I. FerreiraI.M. LimaE.S. de Jesus Amazonas da SilvaM. FernandesC.P. de Faria Mota OliveiraA.E.M. da ConceiçãoE.C. RodriguesA.B.L. FilhoA.C.M.P. CastroA.N. CarvalhoJ.C.T. Anti-inflammatory activity of nanoemulsions of essential oil from Rosmarinus officinalis L.: in vitro and in zebrafish studies.Inflammopharmacology20182641057108010.1007/s10787‑017‑0438‑9 29404883
     [Google Scholar]
  20. Coelho-de-SouzaA.N. Alves-SoaresR. OliveiraH.D. Gomes-VasconcelosY.A. SouzaP.J.C. Santos-NascimentoT. OliveiraK.A. DinizL.R.L. Guimarães-PereiraJ. Leal-CardosoJ.H. The essential oil of Hyptis crenata Pohl ex Benth. presents an antiedematogenic effect in mice.Braz. J. Med. Biol. Res.2021543e942210.1590/1414‑431x20209422 33503203
     [Google Scholar]
  21. KeitaH. dos SantosC.B.R. RamosM.M. PadilhaE.C. SerafimR.B. CastroA.N. AmadoJ.R.R. da SilvaG.M. FerreiraI.M. GiuliattiS. CarvalhoJ.C.T. Assessment of the hypoglycemic effect of Bixin in alloxan-induced diabetic rats: in vivo and in silico studies.J. Biomol. Struct. Dyn.20213931017102810.1080/07391102.2020.1724567 32028848
     [Google Scholar]
  22. FerreiraL. Dos SantosR. OlivaG. AndricopuloA. Molecular docking and structure-based drug design strategies.Molecules2015207133841342110.3390/molecules200713384 26205061
     [Google Scholar]
  23. Custodio de SouzaG. Dias Ribeiro da SilvaI. Duarte VianaM. Costa de MeloN. Sánchez-OrtizB. Maia Rebelo de OliveiraM. Ramos BarbosaW. Maciel FerreiraI. Tavares CarvalhoJ. Acute toxicity of the hydroethanolic extract of the flowers of Acmella oleracea L. in zebrafish (Danio rerio). Behavioral and histopathological studies.Pharmaceuticals (Basel)201912417310.3390/ph12040173 31783553
     [Google Scholar]
  24. Tavares CarvalhoJ.C. DuarteJ.L. FernandesC.P. MoyadoJ.A.V. NavarreteA. CarvalhoJ.C.T. Obtainment and study of the toxicity of perillyl alcohol nanoemulsion on zebrafish (Danio rerio).J. Nanomed. Res.2016440009310.15406/jnmr.2016.04.00093
     [Google Scholar]
  25. FerreiraA.M. da Silva SenaI. CurtiJ. de SouzaA.A. dos Santos LimaP.C. RodriguesA.B.L. da Silva RamosR. de Souza PinheiroW.B. FerreiraI.M. CarvalhoJ.C.T. Trichoderma asperellum extract isolated from brazil nuts (Bertholletia excelsa BONPL): In vivo and in silico studies on melanogenesis in zebrafish.Microorganisms2023114108910.3390/microorganisms11041089 37110512
     [Google Scholar]
  26. SidhuR.S. LeeJ.Y. YuanC. SmithW.L. Comparison of cyclooxygenase-1 crystal structures: cross-talk between monomers comprising cyclooxygenase-1 homodimers.Biochemistry201049337069707910.1021/bi1003298 20669977
     [Google Scholar]
  27. KurumbailR.G. StevensA.M. GierseJ.K. McDonaldJ.J. StegemanR.A. PakJ.Y. GildehausD. iyashiroJ.M. PenningT.D. SeibertK. IsaksonP.C. StallingsW.C. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.Nature1996384661064464810.1038/384644a0 8967954
     [Google Scholar]
  28. OrlandoB.J. MalkowskiM.G. Crystal structure of rofecoxib bound to human cyclooxygenase-2.Acta Crystallogr. F Struct. Biol. Commun.2016721077277610.1107/S2053230X16014230 27710942
     [Google Scholar]
  29. CruzJ.V. NetoM.F.A. SilvaL.B. da S RamosR. da S CostaJ. BrasilD.S.B. LobatoC.C. da CostaG.V. BittencourtJ.A.H.M. da SilvaC.H.T.P. LeiteF.H.A. SantosC.B.R. Identification of novel protein kinase receptor type 2 inhibitors using pharmacophore and structure-based virtual screening.Molecules201823245310.3390/molecules23020453 29463017
     [Google Scholar]
  30. AraújoI.F. MarinhoV.H.S. SenaI.S. CurtiJ.M. RamosR.S. FerreiraR.M.A. SoutoR.N.P. FerreiraI.M. Larvicidal activity against Aedes aegypti and molecular docking studies of compounds extracted from the endophytic fungus Aspergillus sp. isolated from Bertholletia excelsa Humn. &.Bonpl. Biotechnol. Lett.202244343945910.1007/s10529‑022‑03220‑7 35147845
     [Google Scholar]
  31. RamosR.S. BorgesR.S. de SouzaJ.S.N. AraujoI.F. ChavesM.H. SantosC.B.R. Identification of potential antiviral inhibitors from hydroxychloroquine and 1,2,4,5-tetraoxanes analogues and investigation of the mechanism of action in SARS-CoV-2.Int. J. Mol. Sci.2022233178110.3390/ijms23031781 35163703
     [Google Scholar]
  32. van BaarlenP. van BelkumA. SummerbellR.C. CrousP.W. ThommaB.P.H.J. Molecular mechanisms of pathogenicity: how do pathogenic microorganisms develop cross-kingdom host jumps?FEMS Microbiol. Rev.200731323927710.1111/j.1574‑6976.2007.00065.x 17326816
     [Google Scholar]
  33. de Carvalho Rocha KogaR. Custodio de SouzaG. Tavares de Lima TeixeiraA.V. FerreiraA.M. Sánchez-OrtizB.L. Silva AbreuL. Fechine TavaresJ. CarvalhoJ.C.T. Hydroethanolic extracts from Bauhinia guianensis: A study on acute toxicity in Zebrafish embryos and adults.Pharm. Biol.202462157759110.1080/13880209.2024.2374806 39016037
     [Google Scholar]
  34. BrugmanS. The zebrafish as a model to study intestinal inflammation.Dev. Comp. Immunol.201664829210.1016/j.dci.2016.02.020 26902932
     [Google Scholar]
  35. PrataM.N.L. Charlie-SilvaI. GomesJ.M.M. BarraA. BergB.B. PaivaI.R. MeloD.C. KleinA. RomeroM.G.M.C. OliveiraC.C. PimentaL.P.S. JúniorJ.D.C. PerezA.C. Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.Fish Shellfish Immunol.202010123424310.1016/j.fsi.2020.03.044 32240748
     [Google Scholar]
  36. FavachoH.A.S. OliveiraB.R. SantosK.C. MedeirosB.J.L. SousaP.J.C. PerazzoF.F. CarvalhoJ.C.T. Anti-inflammatory and antinociceptive activities of Euterpe oleracea Mart., Arecaceae, oil.Rev. Bras. Farmacogn.201121110511410.1590/S0102‑695X2011005000007
     [Google Scholar]
  37. HanhP.T.B. ThaoD.T. NgaN.T. PhuongN.T. HungL.N. ThienD.T. HaL.M. Toxicity and anti-inflammatory activities of an extract of the Eleutherine bulbosa rhizome on collagen antibody-induced arthritis in a mouse Model.Nat. Prod. Commun.20181371934578X180130072510.1177/1934578X1801300725
     [Google Scholar]
  38. WenigerB. Haag-BerrurierM. AntonR. Plants of Haiti used as antifertility agents.J. Ethnopharmacol.198261678410.1016/0378‑8741(82)90072‑1 7109665
     [Google Scholar]
  39. LansC. Ethnomedicines used in Trinidad and Tobago for reproductive problems.J. Ethnobiol. Ethnomed.2007311310.1186/1746‑4269‑3‑13 17362507
     [Google Scholar]
  40. LinJ. PuckreeT. MvelaseT.P. Anti-diarrhoeal evaluation of some medicinal plants used by Zulu traditional healers.J. Ethnopharmacol.2002791535610.1016/S0378‑8741(01)00353‑1 11744295
     [Google Scholar]
  41. AlvesT.M.A. KloosH. ZaniC.L. Eleutherinone, a novel fungitoxic naphthoquinone from Eleutherine bulbosa (Iridaceae).Mem. Inst. Oswaldo Cruz200398570971210.1590/S0074‑02762003000500021 12973542
     [Google Scholar]
  42. BrasileiroB.G. PizzioloV.R. RaslanD.S. JamalC.M. SilveiraD. Antimicrobial and cytotoxic activities screening of some Brazilian medicinal plants used in Governador Valadares district.Braz. J. Pharm. Sci.2006422195202
     [Google Scholar]
  43. FernandesK. dos SantosE. BatistaC. RibeiroI. PiracelliV. SolciM.C. DuvoisinS.Jr MartinS. SouzaR. MachadoC. WSOC and Its Relationship with BC, levoglucosan and transition metals in the PM2.5 of an Urban Area in the Amazon.J. Braz. Chem. Soc.20223357058110.21577/0103‑5053.20220011
     [Google Scholar]
  44. de Sá HyacienthB.M. Sánchez-OrtizB.L. PicançoK.R.T. PereiraA.C.M. de Sá HyacienthD.C. de SouzaG.C. Rodrigues SarquisR.S.F. AduangaG.M.G. NavarreteA. CarvalhoJ.C.T. Endopleura uchi (Huber) Cuatrec.: A medicinal plant for gynecological treatments – A reproductive toxicity assessment in zebrafish (Danio rerio).J. Ethnopharmacol.202025011245710.1016/j.jep.2019.112457
     [Google Scholar]
  45. RamosR. CostaJ. SilvaR. da CostaG. RodriguesA. RabeloÉ. SoutoR. TaftC. SilvaC. RosaJ. SantosC. MacêdoW. Identification of potential inhibitors from pyriproxyfen with insecticidal activity by virtual screening.Pharmaceuticals (Basel)20191212010.3390/ph12010020 30691028
     [Google Scholar]
  46. RamosR.S. MacêdoW.J.C. CostaJ.S. da SilvaC.H.T.P. RosaJ.M.C. da CruzJ.N. de OliveiraM.S. de Aguiar AndradeE.H. e SilvaR.B.L. SoutoR.N.P. SantosC.B.R. Potential inhibitors of the enzyme acetylcholinesterase and juvenile hormone with insecticidal activity: Study of the binding mode via docking and molecular dynamics simulations.J. Biomol. Struct. Dyn.202038164687470910.1080/07391102.2019.1688192 31674282
     [Google Scholar]
  47. PhamV.C. ShinJ.S. ChoiM.J. KimT.W. LeeK.J. KimK.J. HuhG. KimJ.A. ChooD.J. LeeK.T. LeeJ.Y. Biological evaluation and molecular docking study of 3-(4-sulfamoylphenyl)-4-phenyl-1h-pyrrole-2,5-dione as COX-2 inhibitor.Bull. Korean Chem. Soc.201233272172410.5012/bkcs.2012.33.2.721
     [Google Scholar]
  48. LevitaJ. RositamaM.R. AliasN. KhalidaN. SaptariniN.M. MegantaraS. Discovering COX-2 inhibitors from flavonoids and diterpenoids.J. Appl. Pharm. Sci.2017710311010.7324/JAPS.2017.70716
     [Google Scholar]
  49. BorgesR.S. PalhetaI.C. OtaS.S.B. MoraisR.B. BarrosV.A. RamosR.S. SilvaR.C. CostaJ.S. SilvaC.H.T.P. CamposJ.M. SantosC.B.R. Toward of safer phenylbutazone derivatives by exploration of toxicity mechanism.Molecules201924114310.3390/molecules24010143 30609687
     [Google Scholar]
  50. KrishnaP.S. VaniK. PrasadM.R. SamathaB. BinduN.S.V.S.S. CharyaM.A.S. Reddy ShettyP. In –silico molecular docking analysis of prodigiosin and cycloprodigiosin as COX-2 inhibitors.Springerplus20132117210.1186/2193‑1801‑2‑17223741639
     [Google Scholar]
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Toxicity and Anti-inflammatory Effects of Eleutherine bulbosa (Miller) Urb, Ethanolic Extract, in Zebrafish (Danio rerio)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 24, 199 (2025); https://doi.org/10.2174/0118715230352701241130053455
/content/journals/aiaamc/10.2174/0118715230352701241130053455
/content/journals/aiaamc/10.2174/0118715230352701241130053455
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  • Article Type:     Research Article
Keyword(s): COX; Eleutherine bulbosa; inflammation; Medicinal plants; naphthoquinones; zebrafish

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