Mechanism of Triclosan in the Treatment of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology / 中国医学科学院学报
Acta Academiae Medicinae Sinicae
; (6): 253-261, 2022.
Article
en Zh
| WPRIM
| ID: wpr-927873
Biblioteca responsable:
WPRO
ABSTRACT
Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.
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Texto completo:
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Índice:
WPRIM
Asunto principal:
Triclosán
/
PPAR alfa
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Simulación del Acoplamiento Molecular
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Enfermedad del Hígado Graso no Alcohólico
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Farmacología en Red
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Hígado
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Ratones Endogámicos C57BL
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
Zh
Revista:
Acta Academiae Medicinae Sinicae
Año:
2022
Tipo del documento:
Article