In vivo and in vitro efficacy of crocin against Echinococcus multilocularis.
Animals
Anthelmintics
/ pharmacology
Carotenoids
/ pharmacology
Cell Line
Disease Models, Animal
Echinococcosis
/ drug therapy
Echinococcus multilocularis
/ drug effects
Fibroblasts
/ drug effects
Foreskin
/ cytology
Humans
Male
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Specific Pathogen-Free Organisms
Crocin
Echinococcus multilocularis
Matrix metalloproteinase 2
Matrix metalloproteinase 9
Metacestodes
Protoscoleces
Toxicity
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
13 Jul 2021
13 Jul 2021
Historique:
received:
09
11
2020
accepted:
29
06
2021
entrez:
14
7
2021
pubmed:
15
7
2021
medline:
5
11
2021
Statut:
epublish
Résumé
Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of Echinococcus multilocularis. However, current chemotherapy treatment options are based on benzimidazoles [albendazole (ABZ) and mebendazole], which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease. The anthelmintic effects of crocin were tested on E. multilocularis metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with E. multilocularis. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated. In vitro, crocin had a median effective concentration of 11.36 μM against cultured E. multilocularis metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05 μM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33 ± 3.06% of protoscoleces were killed by treatment with 10 μM crocin for 7 days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50 mg/kg and 100 mg/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode. Crocin was demonstrated to exert parasiticidal activity against E. multilocularis in vitro and in vivo, and can be developed as a novel drug for the treatment of AE.
Sections du résumé
BACKGROUND
BACKGROUND
Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of Echinococcus multilocularis. However, current chemotherapy treatment options are based on benzimidazoles [albendazole (ABZ) and mebendazole], which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease.
METHODS
METHODS
The anthelmintic effects of crocin were tested on E. multilocularis metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with E. multilocularis. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated.
RESULTS
RESULTS
In vitro, crocin had a median effective concentration of 11.36 μM against cultured E. multilocularis metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05 μM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33 ± 3.06% of protoscoleces were killed by treatment with 10 μM crocin for 7 days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50 mg/kg and 100 mg/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode.
CONCLUSIONS
CONCLUSIONS
Crocin was demonstrated to exert parasiticidal activity against E. multilocularis in vitro and in vivo, and can be developed as a novel drug for the treatment of AE.
Identifiants
pubmed: 34256821
doi: 10.1186/s13071-021-04866-4
pii: 10.1186/s13071-021-04866-4
pmc: PMC8278753
doi:
Substances chimiques
Anthelmintics
0
Carotenoids
36-88-4
crocin
877GWI46C2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
364Subventions
Organisme : the National Key Research and Development Program of China
ID : 2017YFD0501306
Organisme : the Qinghai Science and Technology Department Project
ID : 2020-ZJ-Y01
Informations de copyright
© 2021. The Author(s).
Références
Parasite Immunol. 2018 May;40(5):e12523
pubmed: 29518254
Vet Parasitol. 2016 Aug 15;226:38-43
pubmed: 27514881
Pharm Biol. 2018 Dec;56(1):209-216
pubmed: 29540097
Iran J Pharm Res. 2018 Spring;17(2):553-562
pubmed: 29881413
J Enzyme Inhib Med Chem. 2015 Dec;30(6):1027-33
pubmed: 25766747
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Acta Trop. 2014 Dec;140:61-7
pubmed: 25149355
Parasite. 2014;21:70
pubmed: 25526545
Evid Based Complement Alternat Med. 2018 Mar 28;2018:3523126
pubmed: 29785189
Evodevo. 2014 Mar 06;5(1):10
pubmed: 24602211
PLoS Negl Trop Dis. 2016 Mar 11;10(3):e0004535
pubmed: 26967740
Clin Microbiol Rev. 2019 Feb 13;32(2):
pubmed: 30760475
Parasitol Res. 2011 May;108(5):1131-7
pubmed: 21079993
Int J Parasitol. 2010 Nov;40(13):1563-74
pubmed: 20600070
Recent Pat Anticancer Drug Discov. 2016;11(1):121-33
pubmed: 26522014
Int J Parasitol. 2008 Jul;38(8-9):1025-39
pubmed: 18086473
PLoS One. 2020 Sep 11;15(9):e0238909
pubmed: 32915902
J Med Case Rep. 2016 Nov 15;10(1):325
pubmed: 27846915
Res Vet Sci. 2021 Mar;135:517-522
pubmed: 33246571
Korean J Parasitol. 2019 Oct;57(5):517-520
pubmed: 31715693
Parasite Immunol. 1997 Nov;19(11):493-503
pubmed: 9427996
PLoS Negl Trop Dis. 2014 Dec 04;8(12):e3352
pubmed: 25474446
Asian Pac J Cancer Prev. 2012;13(5):2305-9
pubmed: 22901211
PLoS Negl Trop Dis. 2018 Apr 20;12(4):e0006422
pubmed: 29677189
Parasitol Res. 2015 Mar;114(3):1245-6
pubmed: 25645006
Iran J Basic Med Sci. 2020 Jan;23(1):3-12
pubmed: 32405344
Regen Ther. 2020 Oct 22;15:210-215
pubmed: 33426221
Parasit Vectors. 2019 Aug 9;12(1):398
pubmed: 31399141
PLoS One. 2015 May 12;10(5):e0126009
pubmed: 25965910
Vet Parasitol. 2015 Sep 15;212(3-4):193-9
pubmed: 26190130
Environ Sci Pollut Res Int. 2016 May;23(10):9799-808
pubmed: 26856859
Medicine (Baltimore). 2017 Jul;96(27):e7137
pubmed: 28682866
J Visc Surg. 2019 Sep;156(4):291-295
pubmed: 30987848
Eurasian J Med. 2016 Jun;48(2):149-52
pubmed: 27551181
Turk J Med Sci. 2016 Nov 17;46(5):1593-1602
pubmed: 27966333
Saudi J Biol Sci. 2018 May;25(4):747-754
pubmed: 29740240
Int J Cardiol. 2017 Feb 1;228:388-393
pubmed: 27870967
Cytokine. 2015 Sep;75(1):14-24
pubmed: 26044597
Iran J Basic Med Sci. 2017 Feb;20(2):110-121
pubmed: 28293386
J Biomed Res. 2017 Nov 01;:
pubmed: 29219852
Adv Parasitol. 2017;96:259-369
pubmed: 28212790
J Antimicrob Chemother. 2010 Mar;65(3):512-9
pubmed: 20085998
J Thorac Dis. 2019 Nov;11(11):4464-4473
pubmed: 31903234
Parasitology. 2018 Dec;145(14):1929-1937
pubmed: 29781421
Food Waterborne Parasitol. 2019 Mar 14;15:e00040
pubmed: 32095613